In this retrospective study, we report data from two high-volume neurointerventional institutes. We analyzed all DACAA cases treated with FDs between August 2011 and November 2022. We focused specifically on the treatment of aneurysms distal to the AcomA, specifically in the pericallosal and supracallosal segments of the anterior cerebral artery (ACA). We included only cases in which DACAAs were treated exclusively with FD implantation, either as an initial treatment or a follow-up treatment after reperfusion. AcomA aneurysms were not included in this study.

Demographic data; anatomic characteristics; pre- and postprocedural complications; and clinical and angiographic findings from the last available follow-up were recorded for all patients.

All treatments were performed in patients under general anesthesia with a 6 F guiding catheter or 8 F guiding catheter with a 5 F intermediate catheter in cases of severe vessel elongation, with guidance provided by bi-plane digital subtraction angiography (DSA) (Axiom Artis, Siemens, Erlangen, Germany; Azurion, Philips, Eindhoven). The standard approach included femoral access using short sheaths, predominantly on the right side. All FDs were deployed via Trevo Pro 18, Excelsior XT27 (Stryker Neurovascular, Kalamazoo, MI, United States), Headway 21 (MicroVention Terumo, Tokyo, Japan) or Prowler Select Plus (Cerenovus, Johnson & Johnson, New Brunswick, NJ, United States) microcatheters.

All patients undergoing FD procedures received intravenous administration of 3,000–5,000 IU heparin. Heparinized irrigation solutions were used in all catheters (5,000 IU unfractionated heparin/L). FD implantation was performed by the two most experienced interventionalists at each center.

The following types and models of FD were deployed: (1) Silk Vista Baby (Balt Extrusion), (2) Pipeline Embolization Device (PED) (Medtronic), and (3) p64/p64 MW HPC/p48 MW/p48 MW HPC (phenox).

Data were collected over a 12 years period. Most treatments occurred in the final third of this period. Specifically, two EVT treatments from 2011 to 2014, 11 EVT treatments from 2015 to 2018, and 28 EVT treatments from 2019 to 2022 were performed. Not all included FD models were available in each period. During each temporal period, the integrated FD models were not available. Therefore, in each temporal period, attempts were made to use FDs with thinner profiles, or monoplatelet inhibition instead of dual platelet inhibition. The most commonly used FD (p48 MW HPC) in this study, and the only FD that can be introduced in a 0.017″ microcatheter (Silk Vista Baby), were available only in the final third of the 12 years period. p64 and p48 MW were used exclusively in the first 8 years.

FD length and diameter were selected on the basis of 2D- and 3D-calibrated measurements of the distance between the proximal and distal landing zones; the size of the aneurysm neck; and the diameter of the target vessel. Measurements were performed either periprocedurally or during earlier DSA examinations. Measurements were performed on 2D images with maximum zoom in two positions, usually in 90° posterior–anterior and lateral projection, and 45° left and right anterior oblique projection, with bi-planar DSA. If 3D images were available, additional measurements were taken. If the carrier vessel was less than 2 mm thick, the thinnest available FD was selected, such as the p48 HPC MW (2 mm) or Silk Vista Baby (2.25 mm). For larger carrier vessels, the FD size was increased to the next larger diameter. The choice of the required diameter depended primarily on the availability of thin FDs on the market; such FDs were unavailable in the first years of the study. No measurement software was used for the selection of FDs.

Patients to be implanted with p64 HPC or p48 HPC FDs received single antiplatelet therapy (SAPT) with either 1 × 10 mg prasugrel per os (PO) daily for at least 5 days before treatment or a loading dose of 30 mg prasugrel 24 h before the procedure.

Patients receiving uncoated FDs underwent dual antiplatelet therapy (DAPT) including 1 × 100 mg acetylsalicylic acid (ASA) PO daily and 2 × 90 mg ticagrelor PO; 1 × 10 mg prasugrel PO; or 1 × 75 mg clopidogrel PO daily for at least 5 days before treatment. Other patients received a loading dose of 500 mg ASA and 600 mg clopidogrel; 180 mg ticagrelor; or 30 mg prasugrel 24 h before the procedure. A multiplate analyzer (Roche Diagnostics, Mannheim, Germany) and VerifyNow (Accriva, San Diego, CA, United States) were used to assess the sufficiency of platelet inhibition on the day of the intervention and at regular intervals after FD implantation. If the responses to the aforementioned APT regimens were too low or excessive, the doses were modified to twice or half the standard dose, respectively. Patients to be implanted with a p64 HPC or p48 HPC FDs received 1 × 10 mg prasugrel PO daily for 6 months; this regimen was then changed to 1 × 100 mg ASA PO daily. The postprocedural medication of the patients implanted with uncoated FDs included 100 mg ASA PO, to be continued indefinitely, and 1 × 75 mg clopidogrel, 2 × 90 mg ticagrelor or 1 × 10 mg prasugrel PO daily for at least 1 year.

For the long-term treatment, all patients were advised SAPT with 100 mg ASA PO daily lifelong.

Patients were scheduled for clinical and angiographic follow-up examinations as follows: early follow-up at 3–9 months; mid-term follow-up at 12–24 months; and long-term follow-up after 24 months. Assessment of aneurysmal occlusion was recorded according to the O’Kelly Marotta (OKM) scale, on the basis of the degree of aneurysm perfusion (9). Adequate occlusion was defined as OKM grades C or D.

Neurological examinations were performed by a neurologist or a certified stroke nurse within ≤24 h (periprocedural period) as well as during the postprocedural period (>24 h and ≤30 days) and the follow-up (>30 days), according to the modified Rankin Scale (mRS) (10). Morbidity was defined as any permanent deterioration with respect to the baseline mRS.

All patients or their legal representatives provided written informed consent at least 1 day before the procedure, after having been informed of the planned treatment strategy and possible complications. The participants consented to data collection, analysis and anonymous publication of their findings (IRB F-2018-110).

The relevant ethics committee was consulted locally by each center.

Continuous data are described as the mean, median, minimum, and maximum. Hazard ratios with 95% confidence intervals (CIs) were estimated with Cox regression to analyze the influence of aneurysm location on complication probability. Numbers and percentages were used to describe categorical data. Stata/IC 16.1 for Unix was used for the statistical analysis.

The topographic distribution of the DACAAs is shown in Figure 1. The DACAAs treated with FDs in this study were located at (1) the branch point of the ACA into the frontopolar artery; (2) the division point of the ACA into the PA and callosomarginal artery (CMA); the branch point of the PA into the superior parietal artery (3); and (4) the branch point of the CMA into the anterior internal frontal artery.

Forty-one patients diagnosed with DACAAs were treated with FD implants between August 2011 and November 2022 (Table 1). The cohort included 33 females (80%). The mean age of all patients enrolled in the study was 56 years (range 6–81 years). The mean DACAA neck size was 2.31 mm (range 1–6 mm); seven (17%) cases were below 2 mm at maximum diameter, 22 (54%) cases were 2–4 mm, and 11 (27%) cases had a maximum diameter of 4–6 mm (See Figure 2).

Only one FD was implanted per aneurysm. FD implantation was the first treatment for 27 of the aneurysms (66%); in the remaining 14 cases (34%), FDs were used to treat remnants or recurrences after endovascular pretreatment (coil occlusion, n = 12). FD implantation was performed in two cases of acute subarachnoid hemorrhage after rupture of the aneurysm.

Aneurysms were located proximal to the PA bifurcation in 7% (distal A2-segment, n = 3), at the bifurcation of the PA in 73% (n = 30) and distal to the PA bifurcation in 20% (n = 8) of the cases evaluated in this study.

The mean diameters of the distal and proximal landing zones were 1.7 mm (range 0.9–2.5 mm) and 2.0 mm (range 0.9–2.8 mm), respectively. The mean difference in diameters between the proximal and distal landing zones was 0.25 mm (range 0–0.8 mm).

Nine of the implanted FDs (seven p64 classic and two Pipeline) could be introduced only with a 0.027 microcatheter. Probing the DACAA carrier vessel was more challenging with the 0.027 microcatheter than the 0.021 and 0.017 microcatheters. In four of nine cases, because the 0.027 microcatheter could not be directly introduced into segment A3, a thinner microcatheter was used to access the carrier vessel; subsequently, an exchange maneuver with a 300 cm microwire was performed. This process increased the procedure time, radiation time and material use. The documented periprocedural complications occurred after EVTs with 0.027 microcatheters, but we observed no evidence of a direct correlation. No difference in probing or device delivery was observed between the 0.017 and 0.021 microcatheters.

Early follow-up (FU1, 3–9 months) was performed at a median of 146 days post-procedure for all 41 patients (i.e., 41 aneurysms). Complete aneurysm occlusion (OKM D) was observed in 31 (76%) cases. Neck remnants (OKM C) were detected in two (5%) aneurysms. Two cases (5%) exhibited subtotal aneurysmal filling (OKM B), and six (15%) remained unchanged (OKM A). Mild intimal hyperplasia without stenosis was observed in two patients (5%). All 41 patients were asymptomatic at that time.

Mid-term follow-up (FU2, 10–18 months) was performed for 34/41 (83%) of the patients at a median of 340 days. Seven patients who were not scheduled for follow-up at that time had aneurysms graded OKM D at their earlier DSA examination.

Mid-term follow-up DSA revealed complete aneurysm occlusion (OKM D) in 25 of the 34 (74%) patients. One patient’s aneurysm shifted to OKM D from OKM B. Thus, 32 of the original 41 patients (78%) had grade OKM D aneurysms when the seven patients identified as having this grade in FU1 were included. One patient’s aneurysm shifted from OKM B to OKM C, thus resulting in a total of three patients (9%) at this grade. Sac remnants (OKM B) were observed in three aneurysms (9%) that were graded OKM A at FU1. Aneurysms from three of the original six patients remained at OKM A (9%). All 34 patients reviewed at FU2 remained asymptomatic. The two patients who presented with mild intimal hyperplasia at FU1 also showed no change in grade; no additional patients presented with intimal hyperplasia at that time.

Long-term follow-up (FU3, 19–28 months) was performed after a median of 613 days for 22 of the original 41 patients (54%). Sixteen patients were not scheduled for follow-up because their aneurysms were graded OKM D in FU1 and/or FU2; three patients did not appear for scheduled examinations and were not followed up. At FU3, 16 patients with aneurysms graded at OKM D (73%) showed no additional shifts in the scale. Two patients originally diagnosed with neck remnants (OKM C) remained in this condition and showed no changes with respect to former follow-ups. Sac remnants (OKM B) were observed in aneurysms from three patients (14%), including one that shifted from OKM A to OKM B during this interval. Of note, one patient whose aneurysm was formerly graded OKM D presented with reperfusion and conversion to OKM A (5%). This patient underwent a second procedure with an FD device, because the results from the first implantation procedure were considered insufficient. Therefore, we assumed that 31 of the total 41 aneurysms (76%) were graded at OKM D. Intimal hyperplasia improved in the two reported cases; no new in-stent stenosis or intimal hyperplasia developed in any patients in this study. All patients evaluated at FU3 remained asymptomatic.

A final follow-up (FU4, >29 months) was performed after a median of 1,489 days for nine of the original 41 patients (22%). Eighteen patients whose aneurysms were graded OKM C or D at an earlier FU were not scheduled for FU4. Five patients dropped out of the study because of a need for re-treatment, and nine patients were lost to follow-up. At FU4, aneurysms from eight of the nine patients were graded OKM D (89%). One patient’s aneurysm scored as OKM C at an earlier FU and was graded OKM D. Thus, at that time, the aneurysms from 34 of the 41 patients were graded OKM D (83%). One aneurysm with a neck remnant (OKM C) remained unchanged (11%). None of the aneurysms had scores of OKM B or OKM A at that time, and no in-stent stenosis or intimal hyperplasia was observed. All patients evaluated at FU4 were asymptomatic.

The changes in OKM grades at each follow-up visit are summarized in Table 2.

All patients with aneurysms scored at OKM A or OKM B in long-term follow-up (FU3) were advised to undergo re-treatment and were not included in the final follow-up (FU4). An exemplary case is shown in Figure 3.

In these patients, if consented, a second FD was implanted in the carrier vessel under the aneurysm, resulting in sufficient reduction of blood in stream into the aneurysm or complete occlusion within the 6 subsequent months (OKM C or D).

The differences in results among the implanted FDs are shown in Table 3.

Two of the 41 patients (5%) experienced periprocedural complications (24 h after the start of the intervention). One patient developed an intracranial hematoma, probably because of hyper responsiveness to the APT. After surgical treatment and rehabilitation, her neurological status improved to her baseline status of mRS 0 (Figure 4). One patient developed minor ischemia in the ACA territory 8 h after FD implant deployment, which manifested as slightly impaired movement of the contralateral leg. However, by the time of discharge, he had recovered to his baseline mRS of 0. One patient developed a dissection of the ICA during diagnostic runs performed before treatment and was treated by implantation of two flow-diverter stents. The patient developed no neurological deficits associated with the incident. Because this complication was not directly associated with the DACAA treatment, it was not evaluated as an intra- or periprocedural complication in this study.

On pre-discharge magnetic resonance imaging (MRI) scans, silent ischemic microemboli were detected on diffusion-weighted imaging examinations in 12 of 41 patients (29%). However, with the exception of the patient with ACA-associated ischemia discussed above, the remaining 11 patients were asymptomatic on neurological examination. No embolic complications were reported during the procedures.

The patients experienced no complications in the immediate postprocedural phase, and no complications or clinical deterioration during the follow-up period.

The statistical evaluation with regard to possible correlations between the localization of the aneurysm and a complication, the probability of achieving OKM D in the first follow-up in relation to an FD type or the localization did not yield any reliable results and is therefore not presented further.

In the evaluation of the degree of oversizing in relation to closure success, there was a linear descending relationship between the degree of oversizing and the OKM D result in the last follow-up (Figure 5).