Article Information

Hang Yu¹, Khunsa Faiz¹, Sudharsana Rao Ande¹, Janice Linton², Zul Kaderali³, Timo Krings⁴, Jai Shankar^1*

¹Department of Radiology, University of Manitoba, Winnipeg, Canada.

²Indigenous Health Librarian. Neil John Maclean Health Sciences Library, University of Manitoba, Winnipeg, Canada.

³Division of Neurosurgery, University of Manitoba, Winnipeg, Canada

⁴Department of Radiology, University of Toronto, Toronto, Canada

^*Corresponding Author: Jai Jai Shiva Shankar, Department of Radiology, University of Toronto, Toronto, Canada

Received: 24 January 2023; Accepted: 09 February 2023; Published: 04 March 2024

Citation: Hang Yu, Khunsa Faiz, Sudharsana Rao Ande, Janice Linton, Zul Kaderali, Timo Krings, Jai Shankar. Systematic Review of Flow Diversion for Giant and Paraophthalmic Aneurysms: Are Additional Coils Necessary. Journal of Surgery and Research. 7 (2024): 96-106.

Abstract

Keywords

Intracranial aneurysms, Paraophthalmic aneurysms, Intracranial hemorrhage

Article Details

Abbreviations

AComA: Anterior communicating artery

eCLIP: endovascular clip system

FD: Flow diverter

FRED: Flow Re-Direction Endoluminal Device

ICH: Intracranial hemorrhage

mRRC: Modified Raymond-Roy Classification

mRS: modified Rankin Scale

OKM: O’Kelly-Marotta Grading scale

PComA: Posterior communicating artery

PED: Pipeline embolization device

RROC: Raymond-Roy Occlusion Classification

SILK: Silk Flow Diverter

SURPASS: Surpass Flow Diverter

Introduction

Intracranial aneurysms are primarily treated using either endovascular coiling or microsurgical clipping. Since the late 2000s, endoluminal flow diversion was introduced as an alternative treatment option [1]. Instead of intervening on the aneurysm sac with coiling and clipping, flow diversion targets the parent artery. The technique employs flow diverters (FD), endovascular mesh-like devices that are deployed within the parent artery overlying the artery/aneurysm interface. The FD, as its name suggests, diverts blood flow from the aneurysm sac resulting in intra-aneurysm flow stasis. This phenomenon simultaneously reduces sheer stress on the aneurysm wall and promotes intra-aneurysm thrombosis. Additionally, the mesh acts as a scaffold and promotes the propagation and development of endothelial and neointimal cells across the aneurysm neck allowing for reconstruction of the parent artery [2-5]. Flow diversion has comparable rates of aneurysm occlusion, no increase in morbidity or mortality, and similar clinical outcomes compared to coiling [6-11]. Flow diversion is still being more commonly used for aneurysms that are deemed difficult to treat with other endovascular techniques or may be deemed to have higher chances of recurrence [12-19]. While flow diversion is viewed as an alternative to coiling, adjunctive coiling is frequently used during endovascular flow diversion therapy [20-24]. Several FDs are currently available such as the PipelineTM embolization device (PED; Medtronic, Irvine, California), the Silk flow diverter (SILK; Balt Extrusion, Montmorency, France), the Flow Re-Direction Endoluminal Device (FRED; Microvention; Tustin, California) and the Surpass flow diverter (SURPASS; Fremont, CA). While flow diversion is becoming more commonplace, there is some evidence that flow diversion has higher efficacy for treatment of large or giant aneurysm in paraophthalmic location [25-29]. While flow diversion is becoming more commonplace, some studies have suggested the use of adjunctive coils to increase efficacy of flow diversion. It is unclear when to use coils in conjunction with flow diversion and when coils are used, how many coils should be used [28]. Our systematic review aims to answer whether the use of flow diverters alone, without the use of adjunctive coiling, are effective in treating intracranial aneurysms, with a focus on giant and paraophthalmic aneurysms.

Methods

Preliminary searching was done in the Cochrane Library and Scopus databases to identify existing systematic reviews specific to this question, but none were found. To identify relevant studies for inclusion in the analysis, comprehensive searches of the Medline and Embase databases were carried out in June 2019 using the OVID platform. A combination of keyword and MeSH or EMTREE subject headings was used (see online appendix for search strategies). We limited the search to articles published in English before June 2019 with the following inclusion criteria: 1) contained giant intercranial aneurysms (defined as ≥25 mm in diameter) or contained aneurysms of any size within the paraophthalmic region of the ICA, 2) treated with flow diverters with or without additional coils, and 3) had a sample of ≥5 patients.

Two independent screeners extracted the following information using a predetermined data abstraction form: study characteristics, patient demographics, aneurysm characteristics including size, location, and symptoms, flow diverter characteristics, endovascular procedure materials and details, complications of the endovascular procedure, follow-up and imaging, and clinical outcome and degree of aneurysmal occlusion. When available, complete occlusion rates for paraophthalmic aneurysms and giant aneurysm were tabulated separately.

Statistics

Descriptive statistics were performed to calculate mean and proportions. The complete occlusion rate for aneurysms treated with FD alone vs. FD with coils was compared using 2-way ANOVA with an alpha of 0.05. The principle summary measure was the risk ratio and study heterogeneity were measured by I2.

Results

The results are summarized in figure 1. The initial search yielded 387 results, and 289 unique articles after duplicates were removed. Of the original 289 articles, only nine studies were eligible for inclusion within our systematic review [13-21]. A summary of the articles included can be found in table 1.

*Chiu et al had fewer aneurysms than patients because the authors only characterized the 25 successfully treated patients who had 25 aneurysms.

Table 1: Studies included in the systematic review.

Figure 1: Diagram for study selection process

Four studies were prospective and five were retrospective. The nine studies yielded a total of 318 patients with 318 intracranial aneurysms. Patient and aneurysm details are shown in table 2. The sample size ranged from eight to 107 patients, and the number of aneurysms varied between 8 and 109.

*Of the 267 patients that had their ages known.

Table 2: Patient and aneurysm characteristics

Patient characteristics such as age and sex, and aneurysm characteristics including location, size, and type were not available in all studies. While Becske et al. did not characterize their patient population or aneurysm characteristics, the study was a follow-up to their 2013 study which indicated 96 female patients, 35 paraophthalmic aneurysms and 22 giant aneurysms. Carneiro et al. did not provide maximum diameters for the 8 aneurysms they treated but stated that they were either “extremely large” (≥20 mm) or giant (≥25 mm) [4,15]. For aneurysms where maximum diameter and location were known, 58 of 310 (18.7%) were giant aneurysms and 51 of 299 (17.1%) were paraophthalmic aneurysms.

Two hundred eighty-three (89.0%) and 35 (11.0%) of the aneurysms originated from the anterior and vertebrobasilar circulations respectively. Individual aneurysm characteristics were not known for all aneurysms included. Out of 141 aneurysms whose shape were known, 128 (90.8%) were saccular and 11 (7.8%) were fusiform. Out of 171 aneurysms whose neck widths were known, 168 (98.2%) were wide-necked defined as ≥4 mm neck width or dome:neck ratio ≤1. There were 25 (7.9%) bifurcation aneurysms, all of which were from Chiu et al. Both ruptured and unruptured aneurysms were studied; there were 306 (96.2%) unruptured aneurysms and 12 (3.8%) ruptured ones, with seven (2.2%) being acute ruptures and five (1.6%) being previous ruptures.

The 186 (65.3%) symptomatic patients presented with headache, visual disturbances, ocular motor palsies, seizures, hemiparesis, and SAH. Two studies, Becske et al. and Miyachi et al. used the modified Rankin Scale (mRS) for neurological disability to categorize symptoms [18,19].

A variety of FDs were used by the authors and their details are listed in table 3. Overall, 262 (82.4%) aneurysms were treated with PED, 3 (0.9%) with SILK, 28 (8.8%) with Tubridge, and 25 (7.9%) with eCLIP. No aneurysm was treated with two different FDs.

*WEB: Woven EndoBridge Aneurysm Embolization system

Table 3: Flow diverter and endovascular procedure characteristics

Treatment characteristics can also be found on table 3. There were 286 aneurysms that had data on whether they were treated with FD alone or with FD in combination with coils. Of the 286, 213 (74.5%) were treated with FD alone and 72 (25.2%) were treated with FD with coils, including aneurysms previously coiled. One out of 286 was treated with FD alone with prior microsurgical clipping. ReXiaTi et al. treated 31 of their 32 aneurysms with 30 PEDs, but it was unclear how many aneurysms were treated with PED alone versus PED with coils as the authors only state that 12 patients were treated with PED alone and 17 were treated with PED with coils [21]. From the available data, 281 FDs were deployed to treat 184 aneurysms giving a ratio of around 1.5 FDs per aneurysm. The range for number of FDs deployed per aneurysm was 1/3 to 15. In one case, 3 aneurysms were treated with a single PED.

Initial success was documented as either number of patients treated successfully, or number of FDs deployed successfully depending on the study. Initial technical success occurred in 220 of 227 (96.9%) attempted FD deployments. The number was 226 (99.6%) after adjunctive balloon angioplasty for complete opening of the FD. Treatment success occurred in 180 of 216 (83.3%) patients initially and was 183 (84.7%) post balloon assistance.

Three studies provided data regarding side branches occluded by deployment of the FD. Overall, 104 FDs covered 89 side branches and details are available in table 3. Occlusion of side branches were not associated with any neurological deficits or ischemic events.

There were 96 (30.2%) patients who had complications (Table 4). 14 (4.4%) had hemorrhagic and 20 had (6.3%) ischemic complications. Other complications included worsening headaches, worsening cranial neuropathies, bleeding, vision changes, seizures, new aneurysm formation (not a recurrence), and infection. Aneurysm recurrences were not reported in any study. The procedure-related mortality rate is 3.5% (11/318).

Table 4: Complications from flow diverter treatment

All studies included imaging and clinical follow-up, although there was significant heterogeneity in follow-up duration and documenting. Follow-up times ranged from 3 months to 48 months at various intervals at the discretion of the clinician. Five studies included scheduled follow-ups while the other studies only reported on the last follow-up each patient had. For the purpose of this review, follow-up scheduling initially expressed in days or years were all converted to months (e.g. a follow-up time of 180 days, ½ a year, and 6 months were treated the same).

Follow-up imaging included MRA, CTA, and DSA. Occlusion was measured using the Raymond-Roy occlusion criteria (RROC) in two studies, the modified Raymond-Roy occlusion criteria (mRRC) for one study, and the O’Kelly-Marotta Grading scale (OKM) for one study. Clinical outcomes were measured using the modified Rankin Scale (mRS) in two studies while the others used descriptors such as “no deficit/cured,” “improved,” “unchanged” or “worsened.” Follow-up data is summarized in table 5. When available, separate data was given for FD alone vs. FD with coils, and for giant and paraophthalmic aneurysms.

Table 5: Follow-up imaging and clinical findings

Immediately post-procedure, aneurysms treated with FD alone had a complete occlusion rate of 2.9% (1/34) versus 0% (0/18) for those treated with FD and coils. Reported complete occlusion rate for FD alone was 77.0% (117/152) at 6 months, 86.8% (79/91) at 12 months, 100% (13/13) at 14 months, and 93.4% (71/76) at 36 months. Complete occlusion rate for FD with coils was 100% (10/10) at 6 months and remained 100% at 14 months (1/1). There was no significant difference in occlusion rate between FD with coils vs FD and alone at 6 months (RR: 0.99; 95% CI: 0.82-1.19; I2: 0%; p = 0.90). The 13 patients treated with FD alone at 14 months follow-up were all symptom-free. One patient treated with FD and coils at 14 months follow-up was symptom free.

At 6 months, the complete occlusion rate for giant aneurysms was 83.3% (5/6) and was 100% (8/8) for paraophthalmic aneurysms. All the giant aneurysms were treated with FD alone. At 14 months follow-up, 100% (8/8) of patients with known paraophthalmic aneurysms were reported to be symptom-free.

A cohort of 69 aneurysms that only had their latest imaging follow-up reported had a mean follow-up time of 10.7 months. The complete occlusion rate was 37.7% (26/69). Treatment with FD alone had a complete occlusion rate of 70% (7/10) and treatment with FD and coils had a complete occlusion rate of 52.2% (12/23). There was no significant difference between FD with coils and FD alone (RR: 1.69; 95% CI: 0.30 - 9.57; I2: 46%; p = 0.55). There were 28 patients that only had their latest clinical follow-up reported; they had a mean follow-up time of 19.0 months. Of this cohort, 46.4% (13/28) had no deficits, 21.4% (6/28) had improved, and 32.1% (9/28) were unchanged, though 55.6% (5/9) of unchanged patients did experience transient worsening.

Discussion

Our review reported the results of nine studies with a total of 318 patients with 318 aneurysms. The results from this review corroborate previous research regarding the efficacy of FDs in treating intracranial aneurysms. A meta-analysis by Brinjikji et al. which included 1451 patients with 1654 intracranial aneurysms treated with flow-diverter devices found a 6-month occlusion rate of 76%, including a 6-month occlusion rate of 76% for treated giant aneurysms [1]. Procedure-related permanent morbidity was 5% and mortality was 4% [1]. We found a 6-month occlusion rate of 79.7% and a procedure-related mortality rate of 3.5%. Giant aneurysms had a 6-month occlusion rate of 83.3% and paraophthalmic aneurysms had a 6-month occlusion rate of 100%. There was no aneurysm recurrence mentioned in any of the included studies.

Few studies have looked at the use of FDs alone versus FDs with adjunctive coiling. There have been observations of faster occlusion, lower morbidity, and lower incidence of aneurysm rupture with adjunctive coiling [24,25]. We were able to compare the complete occlusion rates for aneurysms treated by FD alone and FD with coils at 6 months (p = 0.90) and 10.7 months (p = 0.55) and found no significant difference. There did not seem to be a difference in morbidity or mortality in the two groups, and clinical outcomes were also similar.

The rate of ischemic and hemorrhagic complications post-procedure was 10.7%, with 6.3% ischemic and 4.4% hemorrhagic. This is similar to other studies which have found ischemic and hemorrhagic complication rates of 5-8% and 2-5% respectively [1,26,27]. 90.9% of all procedure-related deaths were hemorrhagic complications, and 1.6% of patients had permanent deficits from ischemic or hemorrhagic complications post-procedure. Our review also corroborated several other known complications of flow diverters such as side branch and perforator occlusion, perianeurysmal edema, and in-stent thrombosis [2]. Occlusion of perforators and side branches was seen but was clinically silent in all cases. The transient worsening of headaches, cranial neuropathies, and mass effect was attributed in some of our included studies to perianeurysmal edema. Finally, in-stent thrombosis was observed in three patients all presenting with ischemic symptoms such as hemiparesis. None of the three had permanent deficits.

Limitations

There are several limitations to our systematic review. First, all the included studies were observational with the majority of them being retrospective. There were no randomized studies or any with control groups. Selection bias could have been introduced to the sample as the majority of the included studies had small sample sizes, with an average sample size of 35 and with only two studies having a sample size of over 50. Several of the studies also only provided experiences at a single centre.

There was a strong gender bias as 85.4% of the patients were female, although female sex is a risk factor associated with intracranial aneurysms. Additionally, some of the included articles such as Becske et al. and Chiu et al. studied populations with complex and clinically challenging aneurysms, such as bifurcation aneurysms, wide-necked aneurysms, and uncoilable aneurysms [18,20]. As such, the results from those studies may not be generalizable to all patient populations. The complex patient population could explain why Chiu et al. only achieved a treatment success rate of 75.8% whereas all other studies had >90% [20].

Another limitation was that not all of the studies provided all relevant data regarding patient and aneurysm characteristics, parent vessel characteristics, procedure details, and follow-up details. When available, there was no consistent method for data presentation and statistics which made it difficult to compile the data. There were also large amounts of heterogeneity when it came to procedure and follow-up documentation. This was problematic when assessing follow-up data as the studies all had varied follow-up intervals. The follow-up outcome measures also differed widely between studies. Some had aneurysm-centric outcome measures (e.g. number of aneurysms successfully treated) while some had patient-centric measures (e.g. number of patients successfully treated). Overall, the heterogeneity of the included studies made it difficult to compile and compare data.

Conclusion

Flow diverters alone are an effective way to treat intracranial aneurysms, including giant intracranial aneurysms and paraophthalmic aneurysms. The use of coiling in addition to flow diverter for the treatment of intracranial aneurysms has not been shown to be superior to the use of flow diverters alone.

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Appendix

Database: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily <1946 to June 26, 2019>

Search Strategy:

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1 (Giant adj5 aneurysm*).mp. (4575)

2 Intracranial Aneurysm/ (26585)

3 giant.mp. (84277)

4 (Eye* or paraophthalm* or ophthalm* or periocular or ocular or extraocular or orbital or vision* or blind* or optic*).mp. (1373920)

5 (Flow* or diver* or coil*).mp. (1506506)

6 *Embolization, Therapeutic/ (21561)

7 (hydrocoil* or guglielmi*).mp. (858)

8 2 and 3 (1997)

9 1 or 8 (4704)

10 5 or 6 or 7 (1520648)

11 4 and 9 and 10 (135)

***************************

Database: Embase <1974 to 2019 Week 25>

Search Strategy:

--------------------------------------------------------------------------------

1 (Giant adj5 aneurysm*).mp. (5783)

2 exp intracranial aneurysm/ (31663)

3 giant.mp. (95137)

4 (Eye* or paraophthalm* or ophthalm* or periocular or ocular or extraocular or orbital or vision* or blind* or optic*).mp. (1582413)

5 (Flow* or diver* or coil*).mp. (2005521)

6 coil embolization/ (11588)

7 (hydrocoil* or guglielmi*).mp. (1381)

8 2 and 3 (2215)

9 1 or 8 (5999)

10 5 or 6 or 7 (2005575)

11 4 and 9 and 10 (252)

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