1.INTRODUCTION

Endovascular detachable coil embolization of intracranial aneurysms has become an important minimally invasive procedure of management of single or multiple aneurysms in different territories with promising results.1–4 Despite the increase in clinical experiences, innovation of technology and the advertent of new devices, one-stage simultaneously coiling multiple intracranial aneurysms (MIAs) in a segmental parent artery remain challenge and risky in some geographic difficult aneurysms.

Flow diverter (FD) was designed as a single-stent treatment solution for intracranial aneurysm by endoluminal reconstruction instead of aneurysm coiling. Because of better metallic surface coverage than tradition stent with low porosity density, FD had advantage of changing the hemodynamic of parent artery/aneurysm sac, to promote subsequent aneurysm thrombosis.5–11 Complete obliteration (CO) of aneurysms occurred gradually after FD deployment. FD is particularly useful for large (13–24 mm) and giant (>25 mm) broad-neck aneurysms and had the capability of providing the durable angiographic outcomes.

Application of single FD in MIAs has not been well report. The purpose of this study was to report our experiences, hemodynamic and morphologic alteration of using single FD, one-stage managed MIAs in a unilateral parent artery and compared with those patients with single aneurysm treated by FD.

2.METHODS 2.1. Patient demography

From February 2018 to January 2021, a series of 281 patients with 362 unruptured intracranial aneurysms were managed by FD in three institutions by one major operator. Of these patients, 76 patients (29%) had MIAs in a segmental parent artery managed by deployment of single FD; 71 patients had two aneurysms and five patients had three aneurysms. Deployment of FD to treat all aneurysms was achieved in 73 of 76 patients, resulting in a deployment success rate of 96%. From these database, 10 patients were excluded because of lacking follow-up conventional angiography, there were 63 patients with 126 aneurysms were successfully managed by single FD with more than 6-month digital subtraction angiography (DSA) follow-up. There were 49 women (78%) and 14 men (22%) with age between the 42 and 77 years (mean: 59 years). Before initiation of this study, it was approved by IRB of our institute; all patient’s informed consents were obtained from patients and/or patient’s family. Information including sex, age distribution, and characteristics of aneurysms are summarized in Table 1. Seven patients (11%) were symptomatic because of giant aneurysms (n = 6), or large aneurysms (n = 1) compression of nearby cranial nerve or brain stem, leading to decreasing visual acuity or limb weakness. The sizes of the aneurysms varied from 1.8 to 38 mm in their maximal dimension (mean: 5.6 mm) and most (n = 92; 73%) aneurysms were less than 7 mm. The locations of aneurysms were internal carotid artery (ICA, n = 118; 94%), basilar artery (n = 4; 3%), middle cerebral artery (n = 4; 3%). Regarding pharmacological therapy, clopidogrel 75 mg and aspirin 200 mg per day were given for 6 days before embolization.

Table 1 - Demography and characteristics of 63 patients with 126 MIAs managed by single FD Value (%) No of patients with MIAs treated by FD 63 No. of aneurysms 126 Mean age (y) 59 (range 42-77) Gender  Female 49 (78%)  Male 14 (22%) Number of symptomatic patients 7 (11%) Location and number of aneurysms  ICA 118 (94%)  MCA 4 (3%)  BA 4 (3%) Size and number of aneurysms  >25 mm 6 (5%)  13-24 mm 9 (7%)  7-12 mm 19 (15%)  <7 mm 92 (73%) Mean size of aneurysms (mm) 5.6 (range 1.8-38) Adjunctive aneurysm coiling 15 (12%)

BA = basilar artery; FD = flow diverter; ICA = internal carotid artery; MIA = multiple intracranial aneurysms; VA = vertebral artery.

2.2. Endovascular treatment

With patients under general anesthesia, the femoral arteries were catheterized by means of a percutaneous technique. DSA of parent artery, rotational and three-dimensional reconstruction DSA were routinely obtained to evaluate the angioarchitecture of aneurysm and parent artery. A bolus of intravenous heparin of 3000 units was routinely administered after the guiding catheter was placed into parent artery and we maintained an activated clotting time to two times baseline throughout the whole procedure. The 8F femoral sheath and guiding catheter were introduced and navigated into parent artery, then a 6F intermediate catheter was coaxially placed to parent artery as close as possible to aneurysms. The a 2.7F microcatheter was navigated to distal parent artery or its branch, then a proper size and length self-expandable Pipeline flex (n = 16, Medtronic, Irvine, CA, USA) or FRED (n = 47, MicroVention, Tustin, CA, USA) was negotiated and deployed into the parent artery to bridge the aneurysm necks. The stent length was chosen to provide at least a 4 to 5 mm landing zone beyond the aneurysm neck on the proximal and distal parent artery. The stent was sized to equal or 0.2 mm greater than the caliber of the parent vessel at the targeted landing zone. Adjunctive aneurysm coiling was performed to enhance the CO of aneurysms in giant (n = 6), large (n = 9). For adjunctive aneurysm coiling, we accessed to the parent artery and aneurysm sac by puncture of contralateral femoral artery to avoid interfering the microcatheters for FD and coiling, followed by navigation of a 6F guiding catheter to parent artery, the microcatheter was navigated into the aneurysm sac before the stent was deployed (stent-jail catheter technique). After the FD was successfully deployed into target site with the tip of the microcatheter was stabilized in the aneurismal sac, those aneurysms were partially coiling by using the proper size and length of detachable coils.

Postembolization DSA, Dyna-computed tomography (CT) of brain were routinely used to assess hemodynamic alteration of aneurysm sac, patency of the parent artery, and its intracranial branches. CT vessel-wall images were obtained in most patients (n = 56) to evaluate the apposition of FD. We gave clopidogrel 75 mg and 200 mg aspirin daily for 6 months, followed by clopidogrel 75 mg and aspirin 100 mg daily for next 6 months.

2.3. Angiographic analyses

These DSA findings and treatment outcomes of 63 patients of MIAs and 171 patients with single aneurysm were evaluated by two experienced interventional neuroradiologists with 29 and 24 years independently using the same workstation to evaluate the angioarchitectures and treatment outcomes with emphasizing location, number of aneurysms, periprocedural complication, and CO of aneurysm sac. Any discrepancy in the DSA findings of these two interventional neuroradiologists was resolved through reassessment and discussion to make the agreement.

2.4. Statistical analysis

The SPSS statistical software package (version 20) was used for all statistical analysis. Correlations of groups of MIAs and single aneurysm between the age, gender, aneurysm size, working length of FD, CO of aneurysm, adjunctive aneurysm coiling and alteration of periprocedural aneurysm hemodynamic were analyzed using Chi-square test for categorical variables. A two-sided p value <0.05 was considered to be statistically significant. No adjustment of multiple testing (multiplicity) was made in this study.

3. RESULTS

A summary of the data on immediate, follow-up DSA and procedure-related complications, as well as neurologic outcomes are presented in Table 2. Regarding to postembolization hemodynamic alteration of aneurysm sac, immediate CO of aneurysm sac was observed in two (2%), delayed washout of contrast material in the aneurysm sac were found in 90 (71%), unchanged aneurysm hemodynamic in 34 (27%). Four patients (6.3%) had thromboembolic complication because of in-stent thrombosis (n = 3, 4.7%) or distal embolic (n = 1, 1.6%). Patients underwent microcatheter/microguide wire message FD (n = 2) to improve FD apposition and managed by intra-arterial administration of glycoprotein (GP) IIb/III inhibitor to lysis the blood clots (n = 4); the dose of GP was depended on patient’s body weight. The final DSA demonstrated almost total revascularization of partially occlusive parent artery or branches. Clinical follow-up extending longer than 3 months was available in all 63 patients, ranging from 6 to 23 months (mean: 14 months), two patients (3.2%) associated with mild permanent neurologic deficit (mRS = 1). During the follow-up period, no event of late hemorrhage was observed. Follow-up DSA in 63 patients are listed on Table 2, CO of aneurysm (Raymond class I) was observed in 104 aneurysms (83%, Figs. 1–3), subtotal or partial obliteration of aneurysms (class II-III) with residual sac in 18 (14%, Fig. 4), unchanged aneurysm morphology occurred in 4 (3%). In 10 patients with 20 aneurysms, the aneurysms did not synchronize showing morphologic alteration with CO in one, the other one was partial obliteration (Fig. 4). Neurologic outcomes more than 3 months after discharge showed stable in 61 patients; two patients had mRS1 because of sequela of in-stent thrombosis. In comparison with those 171 patients with single aneurysm (Table 3), there is no statistical significance in terms of mid-term of CO of aneurysm, adjunctive aneurysm coiling and immediate alter aneurysm hemodynamic after FD. Longer FD in managing MIAs was found with statistical significance (p = 0.041). The complication and permanent neurologic deficit or death for single FD managed MIAs in our series were 6.3% with 3.2%, these are comparable, but slightly higher than those of single aneurysm of 4% and 2.4% in our series, but no statistical significance.

Table 2 - Angiographic and clinical outcomes of 63 patients of 126 aneurysms successfully managed by single FD Number (%) Immediately DSA outcomes  CO of aneurysm 2 (2%)  Delayed washout of contrast in the aneurysm 90 (71%)  Unchanged of hemodynamic of aneurysm 34 (27%) Follow-up DSA (mean 14 mo)   Obliteration of aneurysm  Raymond class I 104 (83%)  Raymond class II 8 (6%)  Raymond class III 10 (8%)  Unchanged 4 (3%) Patients with synchronize morphology change of aneurysms 53/63(84%) Procedural-related complication (n = 4, 6.3%)  In-stent thrombosis 3 (4.7%)  Distal thrombosis 1 (1.6%) Neurologic outcomes of 63 patients (mean follow-up time) 14 mo  mRS 0 61 (97%)  mRS 1 2 (3%)

CO = complete obliteration; DSA = digital subtraction angiography; FD = flow diverter; mRS = modified Rankin scale (>3 mo after discharge).

Table 3 - Comparison of demography and outcomes of FD managing 63 patients with MIAs and 171 patients with single aneurysm MIA Single aneurysm Total p of MIAs and single aneurysm No. of patients 63 171 234 Age (y) (mean) 59 55 54 0.778 No of aneurysms 126 171 297 Gender  Men 14 (22%) 46 (27%) 60 (26%) 0.580  Women 49 (78%) 125 (73%) 174 (74%) 0.580 Mean size of aneurysm (mm) 5.6 6.4 5.8 0.308 Mean working length of FD (mm) 25 17 21 0.041a CO of aneurysm 104/126 (83%) 131/171 (77%) 235/297 (79%) 0.125 Periprocedural complications 4 (6.3%) 7 (4%) 11 (4.7%) 0.428 Mean DSA follow-up time (mo) 14 13 13 0.928 Adjunctive aneurysm coiling 15/126 (12%) 35/171 (20%) 50/297 (17%) 0.182 Alter aneurysm hemodynamic after FD 90/126 (71%) 131/171 (77%) 221/297 (75%) 0.504

CO = complete obliteration; DSA = digital subtraction angiography; FD = flow diverter; FU = follow-up; MIA = multiple intracranial aneurysm.

Fig. 1:

Patient was a 56-y-old woman, she suffered from headache. A and B, Left internal carotid artery (ICA) conventional and reconstruction digital subtraction angiography (DSA) demonstrated two small aneurysm saccular aneurysms at the left supra-clinoid ICA (arrows). C, Patient underwent flow diverter (FD) to manage these aneurysms. D, Complete obliteration (CO) of aneurysms were demonstrated on 12-mo DSA.

Fig. 2:

Patient was a 61-y-old woman, she had two small asymptomatic aneurysms at the right medial para-clinoid internal carotid artery (ICA). A, Right carotid angiogram confirmed two small wide-neck aneurysms at the right ICA. B and C, Patient underwent flow diverter (FD) to treat these aneurysms and demonstrated complete obliteration of aneurysms on 12-mo postembolization follow-up.

Fig. 3:

Patient was a 50-y-old woman, she had two small asymptomatic aneurysms at the left supra-clinoid internal carotid artery (ICA). A and B, left ICA frontal and reconstruction digital subtraction angiography (DSA) demonstrated two small saccular aneurysms. C, Patient underwent single flow diverter (FD) to treat these two small aneurysms. D, 12-mo post-FD DSA depicted complete obliteration (CO) of aneurysms.

Fig. 4:

Patient was a 53-y-old woman, she had two small asymptomatic aneurysms at the right posterior and medial para-clinoid internal carotid artery (ICA). A, Reconstruction digital subtraction angiography (DSA) demonstrated two small aneurysms at the posterior and medial para-clinoid ICA. B, Patient underwent single flow diverter (FD) to manage aneurysms. C, Reconstruction DSA of 12-mo post-FD demonstrated complete obliteration (CO) of aneurysms of medial para-clinoid ICA, partial obliteration of aneurysm posterior para-clinoid ICA (arrow).

4. DISCUSSION

The reported incidence of MIAs was found in 15% to 35% of patients who presented with SAH.11 The prognosis of patients with MIAs is less favorable outcome than single aneurysm cases after SAH.12 Most series of MIAs have reported a women preponderance (51.5%) than men (31.7%) and higher in patient older than 40 years of age.13 The ruptured risk of MIAs is usually higher than single aneurysm, therefore it is reasonable to treat MIAs in the same session, particularly in those patients with aneurysmal subarachnoid hemorrhage and uncertain of which one is rupture.14

Aneurysm coiling is currently accepted as a standard treatment for ruptured or unruptured intracranial aneurysms and has been increasingly used, regardless of the morphology, location of the intracranial aneurysm. One-stage coiling MIAs distributed in different arterial territories or bilaterally had been reported with promising results.15–17 Coiling each aneurysm in MIAs was considered as combination of single aneurysm embolization. The principle of aneurysm embolization is coiling high-risk aneurysm first or start coiling from distal to proximal aneurysm. These procedures can be performed in a single session using same guiding catheter, microcatheter, and guidewire. The advantages of coiling MIAs in different territories as compare with surgical clipping were well document and included less invasive, cost effective, to avoid repeated general anesthesia and craniotomy. However, if MIAs were in vicinity or located in unilateral parent artery, the treatment strategy may become diverse. The advantage of aneurysm coiling was less and may be ignored because one-stage surgical clipping of these MIAs is feasible.18 On the contrary, coiling MIAs may become more complex and difficult, particularly in those wide-neck MIAs needed stent-assisted technique. To achieve coiling MIAs in this setting by stent-jail technique, the larger-bore guiding catheter is necessary to allow two more microcatheters for coiling and one for stent. Interfering of these microcatheters are common during stent deployment and may lead to dislodge of microcatheter from aneurysm sac into parent artery. The alternative is selection of trans-stent mesh aneurysm catheterization and coiling. Another option is simple coiling or balloon-assisted coiling aneurysms, followed by deployment of stent to eliminate the interfering multiple microcatheter in guiding catheter and parent artery.

FD was first approved for the large or giant wide-neck aneurysms in the ICA to provide the durable angiographic outcomes or for those geographic difficult aneurysms with not amenable to catheterization and aneurysm coiling. The major advantage of FD to aneurysm treatment is not necessary to do aneurysm catheterization and coiling. therefore, the application of single FD to manage MIAs in one segmental parent artery has two major advantages. The first is FD has the potential to save procedure time by abbreviating the time frame of aneurysm catheterization and coiling, also to avoid intraprocedure aneurysm rupture or coil migration/protruding into parent artery causing by these devices.19 The second benefit is that the FD can simultaneously treat two or more aneurysms in one segmental parent artery by deployment single FD, the procedure was almost the same with management of single aneurysm; as in our series, we had treated 29% patients with MIAs in one segmental unilateral parent artery. However, there are some limitations of using single FD to manage MIAs in a parent artery. (1) The maximal working length of current commercially available FD is less than 5 cm, and the working length of FDs were usually less than 4 cm, therefore the distributions of MIAs in the parent artery should within this length. Furthermore, the longer FD with longer foreign body in the parent artery, hence increased the risk or aggravation of thromboembolic complication; also, successful deployment of longer FD may become challenge and difficult due to several curvature has to be overcome such in carotid siphon; (2) the selection of proper diameter and length FD is depended on the diameter of proximal parent artery and aneurysm neck. To minimal the risk of stent migration, the FD should equal or a litter larger diameter than corresponding parent artery to achieve better stent apposition, and to avoid endoleak as well as risk of in-stent thrombosis. However, single FD to manage MIAs is not feasible if the diameter of distal to proximal landing zone of parent artery is larger than 2 mm.20 To achieve better angiographic outcomes, it is better to select two or more proper FDs using telescoped technique to manage MIAs. The landing zone of working length of FD is better greater than 4 mm to ensure the full coverage of aneurysm neck during FD deployment. The other limitation of single FD to manage MIAs is all these aneurysms is nonruptured one, this is because thromboembolic complication may occur in patients lacking of pretherapeutic dual antiplatelet treatment due to aneurysm subarachnoid hemorrhage.

In our series, three patients with three aneurysms failed to coverage by single FD, these led to successful stent deployment to idea position in 96% aneurysm treatment. The success rate of FD deployment in our series was comparable with previously published series, which ranged from 95% to 99%.9 The rate of CO of aneurysm varied from 76% to 81.5% depended on the aneurysm size, location, aneurysm incorporating branch, and follow-up time frame.21–23 One report demonstrated 95% of CO in 5-year follow-up.22 In our series, CO of aneurysms were achieved in 83% of aneurysms in 14-month DSA, this midterm morphologic outcome was comparable with previous published data of FD.14 In this series, simultaneous morphologic change of aneurysm in midterm follow-up DSA in 53 patients and included CO of MIAs of 47 patients with 94 aneurysms (82%), partial obliteration aneurysm in five patients of 10 aneurysms, and unchanged aneurysm morphology in one patient with two aneurysms. In 10 patients (16%) with 20 aneurysms, the aneurysms did not synchronize showing morphologic alteration of aneurysm with one CO, the other one was partial obliteration. All these 20 aneurysms were smaller one with size less than 7 mm and no aneurysm incorporating arterial branch. Therefore, the only possible factor of affecting morphologic change of aneurysm was presumed as different porosity of FD in larger/smaller curvature of different side/location of parent artery. We believe CO may be achieved in longer time frame followed-up in these partial obliteration of aneurysm sacs. The complication and permanent neurologic deficit or death for single FD managed MIAs in our series were 6.3% with 3.2%, these are comparable, but slightly higher than those of single aneurysm of 4% and 2.4% in our series, but no statistical significance. It was presumed as longer FD was selected in the groups of MIAs (25 vs 17 mm), which may associate with higher risk of in-stent thrombosis and difficult to achieve better apposition of stent to arterial wall.

There had two limitations of our study: first, this is a retrospective study done by three institutes. A prospective study is warranted to confirm our observation; the second is the mean angiographic follow-up time is not long enough to justify the real morphologic change of aneurysm after FD.

In conclusion, single FD, one-stage treatment of MIAs in a parent artery was feasible and was proven to be both effective and safe. It can be selected in MIAs with difficult in one-stage coiling or clipping. Morphologic alteration of aneurysm sacs synchronized occurred in most MIAs in a midterm angiographic follow-up. Our results also demonstrated similar endovascular procedure, clinical angiographic and clinical outcomes as compare with those patients with single aneurysm managed by one FD, but longer FD is necessary to manage MIAs.

ACKNOWLEDGMENTS

This study was supported in part by NSC-108-2314-B-075-004-MY2, NSC-111-2314-B-075-023, TVGH-110C-066, and TVGH-108C-033.

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