Safety and efficacy of endovascular treatment for tiny ruptured intracranial aneurysms with low-profile visualized intraluminal support stents

Abstract

Background

Endovascular treatment for tiny ruptured intracranial aneurysms is known to be technically challenging. Thus, we aimed to investigate the safety and efficacy of low-profile visualized intraluminal support (LVIS) stents in the treatment of tiny ruptured intracranial aneurysms.

Methods

From April 2014 to June 2019, among 90 patients with tiny ruptured aneurysms who were treated at our institution endovascularly, 28 underwent stent-assisted coiling with LVIS stents. The clinical and angiographic results were reviewed.

Results

In the LVIS group, complete occlusion was achieved in 27 patients (96.4%). Intraprocedural thrombus formation occurred in 3 patients (10.7%). Follow-up angiography in 24 patients at 6–12 months showed complete occlusion in 23 patients (95.8%) and no aneurysm recurrence. In the coiling-only group, complete occlusion was achieved in 58 patients (93.5%). Intraprocedural aneurysm rupture occurred in 2 patients (3.2%), and postprocedural ischemia occurred in 4 patients (6.5%), with a complication rate of 9.7%. Follow-up angiography in 52 patients at 6–12 months showed complete occlusion in 43 patients (82.7%) and aneurysm recurrence in 7 patients (9.2%). No significant (p > 0.05) differences existed between the two groups.

Conclusions

The LVIS stent is safe and effective in the treatment of tiny ruptured intracranial aneurysms.

Introduction

The results of the International Subarachnoid Hemorrhage Trial (ISAT) have changed the therapeutic strategies for ruptured intracranial aneurysms.^1,2 Compared with clipping, intravascular embolization has lower mortality and disability rates. Tiny ruptured aneurysms are defined as aneurysms with a diameter ≤ 3 mm and have been reported to account for approximately 50% of subarachnoid hemorrhage (SAH) cases.^3,4 However, due to the unique structures of tiny aneurysms, technical difficulties exist in the intravascular treatment of tiny ruptured aneurysms. It has been reported that the intraprocedural rupture rates of tiny aneurysms are 2–5 times higher than those of larger aneurysms.^5,6 These difficulties, including the small size of the aneurysm sac, the stability of the embolization catheter, the reliability of coil detachment, and the conformability of coiling, increase the risk of rupture during the filling process.^7,8

Compared with coiling-only techniques, stent-assisted coiling techniques show similar immediate occlusion rates, with lower recurrence rates and higher long-term angiographic occlusion rates, in addition to higher ischemic stroke and mortality rates. The low-profile visualized intraluminal support (LVIS) stent (MicroVention Terumo, Tustin, California, USA) is a flexible, self-expanding, braided microstent system. Several studies have confirmed that the LVIS stent is safe and effective for the treatment of ruptured and unruptured intracranial aneurysms.^9,10 However, very small numbers of tiny ruptured aneurysms have been included. In this study, we report our experience with the management of tiny ruptured aneurysms by either coiling-only or stent-assisted treatment with LVIS stents to assess their safety and efficacy.

Material and methods

Patients and aneurysms

We retrospectively reviewed the clinical data of 90 patients with tiny ruptured intracranial aneurysms treated endovascularly between April 2014 and June 2019 in our center. Among them, 28 patients underwent stent-assisted coiling with LVIS stents. Aneurysm rupture was demonstrated by computed tomography (CT), and tiny aneurysms were defined based on measurements via digital subtraction angiography (DSA). Ineligible patients were excluded according to the following criteria: dissecting aneurysms or blood-blister-like aneurysms, severe stenosis or occlusion in the parent vessel, and the presence of cerebral arteriovenous malformation or intracranial lesion. We collected baseline clinical data from the patients, including age, sex, medical history, preoperative Hunt-Hess grade, and modified Rankin Scale (mRS) score. In addition, other clinical data were also obtained on aneurysm size and location.

Endovascular procedure

All procedures were performed under general anesthesia and via a transfemoral approach. For wide-necked aneurysms, remodeling balloons or LVIS stents were recommended as assist devices. After sheath placement, to maintain an activated clotting time of 250–350 s, systematic heparinization was individually administered. Then, appropriate coils were implanted into the sac of the aneurysm through a microcatheter. In the patients who underwent stent-assisted coiling, the semi-jailing technique in which the stent was partially deployed to cover the aneurysm neck was used routinely. None of the patients received antiplatelet therapy before surgery. However, in addition to full heparinization during the endovascular procedure, tirofiban was infused after placement of the LVIS stents, and dual antiplatelet therapy was performed during the postoperative period, with 300 mg of both aspirin and clopidogrel on the first day and then 100 mg aspirin and 75 mg clopidogrel daily for six months. Then, drug adjustments were made according to the follow-up results. We measured adequate platelet response by adenosine diphosphate (ADP) and arachnoid acid (AA) aggregation assays. ¹¹ According to the institutional standards, clopidogrel and aspirin response was considered adequate if the ADP-induced aggregation was < 70% (i.e. inhibition was > 30%) and AA-induced aggregation was < 50% (i.e. inhibition was > 50%). Patients were given an additional medication dose if the platelet response was inadequate. Clopidogrel was replaced with ticagrelor 180 mg/day if consistent failure to achieve adequate platelet response. Patients were instructed to take clopidogrel 75 mg/day (or ticagrelor 180 mg/day) for six months and aspirin 100 mg/day for one year to prevent thrombosis and stent stenosis. For patients who received coiling only, antiplatelet therapy was not recommended. After the operation, the lumbar puncture was considered for patients who underwent stent-assisted coiling with hydrocephalus and intraventricular hemorrhage. The external ventricular drainage procedure was only recommended for patients who received coiling only.

Clinical and angiographic follow-up

After surgery, the following data were collected on the coils, assist devices, complications, and angiographic images. MRI and CT scans were performed 24 h post-intervention. DSA was recommended at the 6-month follow-up. The degree of aneurysm occlusion was assessed according to the 3-class Raymond scale (complete occlusion, neck remnant, and residual aneurysm). The recurrence rate and the mRS score were also obtained during the follow-up period. Additionally, the total coil length and coil packing density were recorded. The coil packing density was defined by dividing the coil volume by the aneurysm volume. ¹² The coil volume was determined by using the formula V = π (d/2)² L, where d is the coil diameter, and L is the coil length. Aneurysm volume was calculated by using the formula V = 4/3π a b (a + b)/2, where a and b are half of the long and short axes of the aneurysm.

Statistical analysis

The baseline characteristics of the patients were compared between groups. Medians with interquartile ranges were used for continuous variables, and proportions were used for categorical variables. The t-test or Mann-Whitney U test was used for continuous variables, and the χ2 test or Fisher's exact test was used for categorical variables. The complete occlusion rate and the recurrence rate were studied by using the χ2 test or Fisher's exact test The number of adverse events was compared by using the Fisher's exact test All analyses were performed using SPSS version 23 (IBM, Armonk, New York). All tests were two-sided, and p < 0.05 was considered statistically significant.

Results

Baseline characteristics

A total of 90 patients with tiny ruptured aneurysms were included in the study. The baseline characteristics of the patients and the aneurysms are shown in Table 1. Twenty-eight patients were assigned to the LVIS group, and seventy-two patients were assigned to the coiling-only group. The two groups were comparable. There were no significant differences in the baseline characteristics between the two groups.

Table 1.

Baseline characteristics of the patients and the aneurysms.

Characteristics	Coiling-only N = 62	Stent-assisted N = 28
Sex ratio (male/female)	25:37	13:15
Mean age (year)	57.10 (10.65)	53.96 (9.14)
Aneurysm location
Anterior circulation	52 (83.9%)	26 (92.9%)
Posterior circulation	10 (16.1%)	2 (7.1%)
Aneurysm size (mm)	2.46 (0.43)	2.53 (0.39)
Aneurysm neck (mm)	1.63 (0.48)	1.99 (0.59)
Dome: neck ratio
≥ 1.5	53 (85.5%)	9 (32.1%)
< 1.5	9 (14.5%)	19 (67.9%)
Packing density (%)	41.76 (28.71%)	38.18 (24.32%)
Hunt-Hess grade
I	29 (46.8%)	12 (42.9%)
II	26 (41.9%)	10 (35.7%)
III	6 (9.7%)	5 (17.9%)
IV	1 (1.6%)	1 (3.6%)

Data are No. (%) or mean (SD).

For the LVIS group, the mean age was 54.0 ± 9.1 years. Thirteen of the patients were male, while fifteen were female. Among the twenty-eight patients, seventeen had a history of hypertension. The mean aneurysm size was 2.53 ± 0.39 mm, and the mean aneurysm neck was 1.99 ± 0.59 mm. Twenty-six aneurysms (92.9%) were located in the anterior circulation, and 2 (7.1%) were located in the posterior circulation. Twelve patients demonstrated Hunt-Hess grade I, ten demonstrated Hunt-Hess grade II, five demonstrated Hunt-Hess grade III, and one demonstrated Hunt-Hess grade IV SAH. The mean packing density was 38.18 ± 24.32%.

For the coiling-only group, the mean age was 57.1 ± 10.7 years. Twenty-five of the patients were male, while thirty-seven were female. Among the sixty-two patients, thirty-eight had a history of hypertension. The mean aneurysm size was 2.46 ± 0.43 mm. Fifty-two aneurysms (83.9%) were located in the anterior circulation, and ten (16.1%) were located in the posterior circulation. Twenty-nine patients demonstrated Hunt-Hess grade I, twenty-six demonstrated Hunt-Hess grade II, six demonstrated Hunt-Hess grade III, and one demonstrated Hunt-Hess grade IV SAH. The mean packing density was 41.76 ± 28.71%.

Perioperative complications

The perioperative complications are presented in Table 2. Perioperative complications occurred in three patients treated with the LVIS stent compared with six patients treated with the coiling-only technique. There was no statistically significant difference in perioperative complications between the two groups. No postoperative ischemia occurred in patients treated with the LVIS stent, but intraprocedural thrombus formation occurred in three patients. All three patients were recanalized after treatment with tirofiban. Intraprocedural aneurysm rupture occurred in two patients treated with the coiling-only technique, and postoperative ischemia occurred in four patients. One ruptured patient died, but other patients recovered well after medical therapy and rehabilitation.

Table 2.

Clinical outcomes of the patients and degree of the aneurysm occlusion.

Outcomes	Coiling-onl N = 62	Stent-assisted N = 28	p Value
Perioperative complications	6 (9.7%)	3 (10.7%)	0.880
Intraprocedural aneurysm rupture	2 (3.2%)	0
Intraprocedural thrombus formation	0	3 (10.7%)
Postprocedural ischemia	4 (6.5%)	0
Immediate angiography
Complete occlusion	38 (61.3%)	15 (53.6%)	0.499
Incomplete occlusion	24 (38.7%)	13 (46.4%)
Imaging following angiography	52 (83.9%)	24 (85.7%)	0.822
Follow-up time (month)	7.00 (1.71)	7.92 (2.34)	0.116
Complete occlusion	43 (82.7%)	23 (95.8%)	0.156
Incomplete occlusion	9 (17.3%)	1 (4.2%)
Recurrence rate	3 (5.8%)	0

Data are No. (%) or mean (SD). p < 0.05 was considered statistically significant.

Immediate and follow-up angiographic results

The angiographic results are presented in Table 2. On immediate angiography, the aneurysm complete occlusion rate was 96.4% for the LVIS group and 93.5% for the coiling-only group. For the LVIS group, angiographic follow-up was available for twenty-four patients, and the mean time was 7.92 ± 2.43 months. For the coiling-only group, angiographic follow-up was available for fifty-two patients, and the mean time was 7.00 ± 1.71 months. At the follow-up angiography, the aneurysm complete occlusion rate was 95.8% for the LVIS group and 82.7% for the coiling-only group. The recurrence rate was 0 for the LVIS group and 13.5% for the coiling-only group. At immediate and follow-up angiography, there was no significant difference between the groups in terms of the complete aneurysm occlusion rate or the recurrence rate. However, patients with recurrence were not retreated and were told to check in regularly (Figures 1 and 2).

Figure 1.

Demonstrative angiographic images of a ruptured tiny basilar artery aneurysm. (A) Three-dimensional reconstruction of the aneurysm. (B) Position of the Echelon 10 microcatheter (black arrow) and the Selectplus microcatheter (white arrow). (C) Partially deployed of the LVIS stent during the coiling procedure. (D) Completely expanded of the LVIS stent. (E) Successful occlusion of the aneurysm immediately after the procedure. (F) Maintained adequate occlusion at the 6-month follow-up.

Figure 2.

Demonstrative angiographic images of a ruptured tiny anterior cerebral artery aneurysm. (A) Three-dimensional reconstruction of the aneurysm. (B) Aneurysm in the working projection before treatment. (C) Position of the Echelon 10 microcatheter (black arrow) and the Selectplus microcatheter (white arrow). (D) Partially deployed of the LVIS stent during the coiling procedure. (E) Successful occlusion of the aneurysm immediately after the procedure. (F) Maintained adequate occlusion at the 7-month follow-up.

Discussion

The International Study of Unruptured Intracranial Aneurysms (ISUIA) results have shown that many factors are involved in managing patients with unruptured aneurysms. For patients with unruptured intracranial aneurysms less than 7 mm in diameter in the anterior circulation, the rupture rate is about 0.1% per year. ¹³ However, regular follow-up is recommended for tiny unruptured aneurysms, especially for patients who have had a previous SAH. Although a number of studies have been conducted to evaluate the safety and efficacy of the endovascular treatment of tiny ruptured intracranial aneurysms, the safety and efficacy of the LVIS stent are not known. Our results showed high rates of complete occlusion in the LVIS group, both immediately after surgery and during follow-up. According to a meta-analysis by Yamaki et al. technical success was achieved in 92% of patients, and 7% of aneurysms were retreated. ¹⁴ In our study, technical success was achieved in all patients, and none of the aneurysms were retreated.

The first stent used for intracranial aneurysm embolization was the Neuroform stent (Stryker). Since then, other intracranial stents such as Enterprise (Codman), Leo (Balt) and Solitaire (Ev3) have been successively used in clinical practice. Although these stents have some differences in performance and design, stent selection is still based on clinical experience and operational techniques. The LVIS stent is a third-generation stent designed for coiling-assisted embolization and is a self-expandable stent made of single nitinol. ¹⁵ The proximal and distal ends of LVIS stents are labeled with trumpet-like radiopaque metal, and two tantalum wires provide visibility of the whole stent. Compared with other traditional stents, the LVIS stent has higher metal coverage (23%), which provides a good flow-diverting effect. ¹⁶ Although LVIS Junior stent may be a good choice for small parent arteries, we, unfortunately, did not have this stent. The novel LVIS EVO (MicroVention Terumo, Tustin, California, USA) stent is the second-generation version of the LVIS Junior stent, which officially appeared on the market in 2020. The stent has a nitinol exterior and a platinum core and is available in diameters ranging from 2 to 4 mm and lengths ranging from 12 to 34 mm. Its wires are visible in fluoroscopy via the DFT (drawn-filled tube) braid technology, which facilitates stent deployment and good wall-apposition.^17,18

Nowadays, flow-diverting stents also offer a promising endovascular treatment option for complex aneurysms. The Pipeline Embolization Device (PED; Covidien, Irvine, California, USA) is the most widely used flow-diverting stent and has been increasingly used for off-label indications. The results of the Prospective Study on Embolization of Intracranial Aneurysms with the Pipeline Device (PREMIER) have shown high rates of complete occlusion without significant parent vessel stenosis and low rates of permanent neurologic complications in the treatment of unruptured wide-necked small /medium aneurysms (≤12 mm). ¹⁹ By comparing PED with stent-assisted coiling patients with unruptured, small (<10 mm) aneurysms, Chalouhi et al. reported that the two groups had similar periprocedural risks, clinical outcomes, and angiographic results. ²⁰ Although similar results were found by Bhogal et al. flow diverting stents were not recommended as first-line treatment. ²¹ The main advantage of flow diverting stents did not need to access the sac of tiny aneurysms. However, advances in imaging, increasing operator experiences, and the widely used adjunctive devices have all made the coiling of tiny aneurysms routinely and feasibly. Besides, the cost of flow diverting stents was far higher than standard endovascular coiling in China. Thromboembolic complications remained another issue for flow diverting stents. Hanel et al. reported their experience in using a new surface-modified flow diverting stent to treat a ruptured fusiform aneurysm located in the posterior circulation. ²² In this case, only a loading dose of aspirin (325 mg) was given two hours before the procedure. Then the ruptured fusiform aneurysm was treated using a combination of two Pipeline Shield devices (Covidien, Irvine, California, USA) and coils. Although the Pipeline Shield device has demonstrated a significant reduction in thrombogenicity in vitro, angiography showed the stents occlusion at ten-days follow-up. ²³ Well-controlled studies in the future were needed for validation.

Intraoperative aneurysm rupture is a serious complication in the endovascular treatment of ruptured tiny aneurysms. The small size of the aneurysm sac limits the movement of the microcatheter. ²⁴ Any unexpected movement during microcatheter implantation and coil packing can lead to the rupture of the aneurysm sac. Initial study results show that the intraoperative rupture rate ranged from 9% to 11%, while recent studies have shown a reduced risk of approximately 3% to 4%.^25,26 In our study, there were two cases of intraoperative rupture in the coiling-only group. This may be due to newer technological advances and increased experience. In addition, advances in technology for smaller and softer coils could also have contributed to the results. The coil packing density was suggested to be reduced, which will allow slow thrombus formation in the sac.^27,28 In the study, the coil packing densities in the two ruptured patients were 14.4% and 101.9%. The former ruptured patient died because the tip of the microcatheter could not enter the sac again. However, the latter patient recovered well after dense embolization.

Although the use of LVIS stents can facilitate coil packing, it may increase the incidence of ischemic events. Our results showed that intraprocedural thrombus formation occurred in three patients, which is similar to that of reported by Gao et al. (10.7% vs. 9.1%, respectively). ⁹ We speculated that this may be related to poor wall apposition and inadequate antiplatelet application.^29,30 However, all three patients were recanalized after treatment with tirofiban. No postoperative ischemia occurred in patients treated with the LVIS stent. However, in the coiling-only group, postoperative ischemia occurred in four patients (6.5%). The LVIS stent has a smaller mesh (< 0.9 mm) and can effectively prevent small coils from protruding into the parent artery. The study results showed that the postoperative ischemia rate ranged from 2% to 9% in the coiling-only treatment of tiny ruptured aneurysms.^31,32 Unlike in several other studies, all four patients recovered well after medical therapy and rehabilitation.

Our results showed lower recurrence rates in the LVIS group than in the coiling-only group during long-term follow-up. Although there was no significant difference in the mean packing density between the two groups, the rate was lower in the LVIS group. The LVIS stent has high metal coverage, inducing additional thrombus within the aneurysm sac and rapid endothelialization on the stent surface.^9,16 Moreover, to achieve complete stent expansion, we pushed the stent at the neck of the aneurysm, leading to denser metal coverage.

None of the patients received antiplatelet therapy before surgery. In addition to full heparinization during the endovascular procedure, tirofiban (8 mL) was injected intravenously before placement of the LVIS stents and infused at 6 mL/h speed, according to our experience. ¹¹ We were very strict with confirming the therapeutic effect of antiplatelet therapy by using adenosine diphosphate (ADP) and AA aggregation assays. We believe this has significantly reduced the number of ischemic events in our series. For unruptured aneurysms, we prefer to be given dual antiplatelet therapy, consisting of 75 mg/day clopidogrel and aspirin 100 mg/day for five days. Then adequate platelet response was measured. Patients were given an additional medication dose if the platelet response was inadequate. Clopidogrel was replaced with ticagrelor 180 mg/day if consistent failure to achieve adequate platelet response.

Only tiny ruptured saccular aneurysms were involved in this study, so the results only represent the treatment of one particular type of aneurysm. In addition, although we included aneurysms in the posterior circulation, there were only two cases of such aneurysms in the LVIS group. Studies on the use of the LVIS stent in the treatment of tiny ruptured aneurysms in the posterior circulation should be performed.

Conclusions

The LVIS stent is safe and effective in the treatment of tiny ruptured intracranial aneurysms.