Eisuke Tsukagoshi, Hiroki Sato, Shinya Kohyama
  1. Department of Endovascular Neurosurgery, Saitama Medical University International Medical Center, Hidaka, Japan.

Correspondence Address:
Hiroki Sato, Department of Endovascular Neurosurgery, Saitama Medical University International Medical Center, Hidaka, Japan.


Copyright: © 2022 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Eisuke Tsukagoshi, Hiroki Sato, Shinya Kohyama. Delayed aneurysm rupture in a patient treated with flow redirection endoluminal device: A case report and literature review. 04-Nov-2022;13:506

How to cite this URL: Eisuke Tsukagoshi, Hiroki Sato, Shinya Kohyama. Delayed aneurysm rupture in a patient treated with flow redirection endoluminal device: A case report and literature review. 04-Nov-2022;13:506. Available from:

Date of Submission

Date of Acceptance

Date of Web Publication


Background: Delayed aneurysm rupture after flow-redirection endoluminal device (FRED) implantation is rare. We report a case of internal carotid-cavernous fistula (CCF) caused by a delayed aneurysm rupture of the cavernous portion of the internal carotid artery (ICA) after FRED implantation.

Case Description: A 75-year-old woman had a gradually enlarging aneurysm at the C4 portion of the left ICA. We performed FRED implantation for the same. The FRED implantation procedure was smooth and the FRED expanded well and attached to the vessel wall. Five days after surgery, the patient developed a strong headache, hyperemia of the left eye, and disturbance of the left eye movement. Magnetic resonance imaging and angiography revealed a left CCF with cortical venous reflux. We performed transarterial aneurysmal and transvenous cavernous sinus embolization. Postoperatively, angiography showed no fistula and complete occlusion of the aneurysm; however, minor eye movement disorder persisted.

Conclusion: To prevent the development of delayed aneurysm rupture in patients treated with FRED, preoperative consideration of whether to add coil embolization is important, even if the aneurysm is located in the C4 portion of the ICA and there is no risk of subarachnoid hemorrhage, including the size of aneurysm. In this report, we have tried to alert surgeons regarding the risk of delayed aneurysm rupture due to FRED implantation.

Keywords: Carotid cavernous fistula, Delayed aneurysm, Flow-redirection endoluminal device, Internal carotid artery


Balloon- or stent-assisted coil embolization is a known endovascular treatment of wide-necked aneurysms. However, these treatments are limited by associated aneurysm recurrence rates.[ 7 ] The use of a flow diverter (FD), such as a pipeline embolization device (PED) (Medtronic, Minnesota, USA), is a favorable treatment for these aneurysms with high rates of complete occlusion.[ 6 ] Similarly, the use of a flow-redirection endoluminal device (FRED) (MicroventionTerumo, California, USA), an FD consisting of two layers, is also safe with a high rate of complete occlusion.[ 13 , 18 ] However, in the treatment of aneurysms with FDs, delayed aneurysm rupture — defined as rupture of the target aneurysm after the deployment of the FDs — is a fatal complication, with a reported occurrence of 0.3–4%.[ 1 , 4 ] A risk factor for delayed aneurysm rupture is large or giant aneurysms.[ 12 ] However, few cases of PED implantation for relatively small aneurysms resulted in delayed aneurysm rupture,[ 9 ] but none of these cases had FRED implantation. Herein, we report a case of delayed aneurysm rupture that occurred after FRED placement.

Written informed consent to publish this report was obtained from the patient before the submission process.


A 75-year-old woman (height: 148 cm, weight: 55 kg) was diagnosed with a gradually enlarging left internal carotid artery (ICA) aneurysm by magnetic resonance imaging (MRI). There were no neurological dysfunctions and no preexisting conditions. The aneurysm was a saccular aneurysm at the C4 portion of the ICA with a size of 9.4 mm × 9.1 mm, a neck of 8.0 mm, and a depth of 6.4 mm (aspect ratio of 0.8) [ Figures 1a and b ]. Antiplatelet therapy with 100 mg of aspirin and 75 mg of clopidogrel was initiated, and surgery was performed 29 days thereafter. Platelet aggregation capacity was measured by transmission method 1 day before the surgery. Since aspirin showed slightly low aggregation ability, 100 mg of cilostazol was additionally administered the day before and on the day of the endovascular surgery.

Figure 1:

(a) Magnetic resonance angiography showing an unruptured aneurysm at the cavernous portion of the left internal carotid artery. (b) 3D rotated angiography showing a saccular aneurysm at the C4 portion, with a size of 9.4 mm × 9.1 mm, a neck of 8.0 mm, and a depth of 6.9 mm (aspect ratio of 0.8). (c) Cone-beam computed tomography performed after the procedure shows a stent fitted well into the artery.


A 6Fr Axcelguide (Medikit, Tokyo, Japan) was placed at the left ICA. Headway 27 (Microvention-Terumo, California, USA) and CHIKAI 14 (ASAHI INTECC, Aichi, Japan) were inserted into SOFIASELECT (Microvention-Terumo, California, USA) and guided to the C1 portion of the ICA. We placed the FRED (5.0 mm × 26 mm) from the origin of the ophthalmic artery to the C5 portion of the ICA to cover the neck of the intracranial aneurysm. The FRED expanded well. Post-dilatation was not performed as cone-beam computed tomography showed that the stent fitted well into the artery [ Figure 1c ]. A comparison of pre and postoperative angiograms showed that the contrast did not enter into the inflow zone of the aneurysm in the arterial phase [ Figures 2a and b ]. In the capillary phase, there were areas of contrast stagnation [ Figures 2c and d]. Coil embolization was not performed as there was no risk of subarachnoid hemorrhage due to the location of the aneurysm at the C4 portion of the ICA.

Figure 2:

(a) Left internal carotid arteriography before the procedure in the arterial phase. (b) Arterial phase after the procedure showing partial areas with no inflow of contrast that were present within the aneurysm. (c) Capillary phase before procedure showing no stagnation of blood flow within the aneurysm. (d) Capillary phase after the procedure showing stagnation within the aneurysm.


After the intervention, in addition to continuing oral aspirin 100 mg and clopidogrel 75 mg, argatroban 60 mg was administered over 24 h. There were no obvious findings of neurological deficits. The patient was discharged 3 days after the surgery. However, 2 days after discharge, the patient came back to our hospital with a strong headache. Conjunctival hyperemia of the left eye as well as left oculomotor nerve and trochlear nerve palsy was noted. MRI showed the occurrence of a left internal carotid-cavernous fistula (CCF; Figure 3a ) due to rupture of the treated aneurysm. Cerebral angiography showed venous reflux into the superior ophthalmic vein (SOV) and superficial middle cerebral vein [ Figure 3b ]. Therefore, to prevent intracranial hemorrhage, endovascular treatment was performed.

Figure 3:

(a) Magnetic resonance angiography showing left internal carotid-cavernous fistula. (b) Left carotid angiography showing reflux into the superior ophthalmic vein and superficial middle cerebral vein. (c) Left carotid angiography after the procedure shows little flow to the cavernous and inferior petrosal sinuses and no cortical reflux. Therefore, we decided to complete the transvenous embolization.


First, transarterial coil embolization of the ruptured aneurysm was attempted with the transcell technique. A 6Fr Axcelguide (Medikit Tokyo, Japan) was placed at the left ICA. We tried to advance the CHIKAI 14 and Headway Duo (Microvention-Terumo, California, USA) into the aneurysm through the stent mesh using a 4.2Fr FUBUKI (ASAHI INTECC, Aichi, Japan) as an intermediate catheter, which was pushed strongly against the stent. However, the Headway Duo was never advanced through the stent mesh along the CHIKAI 14, which easily went into the aneurysm. Thereafter, the CHIKAI 10 and Marathon (Medtronic, California, USA) were advanced into the aneurysm through the stent mesh after several attempts. Because only iED coils (Kaneka Medics, Kanagawa, Japan) smaller than 4 mm in size were able to pass through the Marathon, the aneurysm was not packed completely due to compartment formation, and the shunt flow was not stopped. Therefore, additional embolization with 50% n-butyl-2-cyanoacrylate was performed. However, the CCF appeared to persist on the left ICA angiography. For this reason, transvenous embolization was performed. A 7-Fr Guider (Stryker, Michigan, USA) was placed to the left inferior petrosal sinus. Headway Duo and a 45° pre-shaped Excelsior SL-10 (Stryker, Michigan, USA) were placed through the cavernous sinus and the SOV, respectively. Coil embolization of the SOV and cavernous sinus was performed. Although the shunt remained after the procedure, cortical venous reflux disappeared [ Figure 3c ].

After the intervention, the patient continued to take aspirin 100 mg and clopidogrel 75 mg. The conjunctival hyperemia and trochlear nerve palsy improved, although the oculomotor nerve palsy persisted. A head MRI showed the disappearance of shunt flow. The patient was discharged 12 days after the intervention with slight left oculomotor nerve palsy (modified Rankin Scale 1); however, the symptoms improved 6 months after the intervention. The angiogram showed complete occlusion of the aneurysm and CCF, and 1 year after the surgery, only a slight eye movement disorder remained. The cerebral angiograms showed no lesion recurrence.


We reported a case of delayed aneurysm rupture that occurred after FRED placement despite the aneurysm having a low risk of delayed rupture. We attempted to alert the surgeons to the risk of delayed aneurysm rupture with FRED implantation to avoid a worse prognosis resulting from rupture. The FRED, which has been in use since 2012, has been reported to be effective and safe.[ 5 , 15 - 17 ] However, there is a report of a poor outcome of delayed rupture of large intracranial aneurysm with FRED implantation.[ 17 ] Rouchaud et al.[ 18 ] reported poor prognosis of delayed aneurysm ruptures, with 81.3% experiencing death or poor neurological outcome, furthermore, Hou et al.[ 9 ] reported that 9.5% of patients survived regardless of subsequent treatment. We believe that this report of potentially serious complications serves as a reminder for surgeons in the field.

According to our literature review, six cases of delayed rupture of aneurysms caused by the placement of a FRED have been reported.[ 11 , 14 , 15 , 17 ] Based on these previous reports, the incidence of delayed rupture of intracranial aneurysm after placement of a FRED is believed to be 0.3–1.3%. Including our case, seven cases of delayed rupture of aneurysm after placement of a FRED have been reported to date [ Table 1 ]. In all cases, the delayed aneurysm rupture occurred within 5–233 days (median 35 days) postoperatively. Further treatment was performed in three cases, including our case. In two cases, additional FD implantation was performed.

Table 1:

Cases of delayed aneurysm rupture after FRED implantation reported to date.


Regarding the Silk FD with single-layer braided design, the risk factors for delayed aneurysm rupture include large or giant aneurysms, symptomatic aneurysms, aspect ratio >1.6, and jet blood flow in the aneurysm.[ 12 ] However, the risk factors associated with delayed aneurysm rupture of a FRED have not yet been identified. Hou et al.[ 9 ] reported six cases of bleeding in PED implanted cases with aneurysms smaller than 10 mm; delayed aneurysm rupture in FRED implantation was not observed. No reports of delayed aneurysm rupture smaller than 10 mm were noted in review articles that reported only FRED implantation cases.[ 15 , 16 ] In the present case, we performed FRED placement for an aneurysm in the cavernous sinus of the ICA with an aspect ratio of 0.8. In addition, after placement of the FRED, jet blood flow was not suspected on imaging. Despite the limited risk factors for delayed aneurysm rupture, the risk of it occurring must always be kept in mind.

Some causes of delayed aneurysm rupture after FD implantation have been reported to be due to increased pressure in the aneurysm due to rapid thrombosis,[ 3 ] weakening of the aneurysm wall due to inflammation caused by thrombus in the aneurysm,[ 12 ] migration of the FD into the aneurysm, and damage to the arterial wall during the procedure.[ 2 ] In this case, there was no migration of the FRED into the aneurysm or damage to the arterial wall. Therefore, the cause of the delayed aneurysm rupture may have been rapid thrombosis or the inflammation of the aneurysm. It is unclear whether rapid thrombosis occurred immediately after implantation. However, Figure 2 suggests the possibility that the thrombosis occurred during the 5 days before the rupture.

For the prevention of delayed aneurysm rupture, there is no definite consensus on whether FD placement should be combined with coil embolization of the aneurysm or additional FD placement. With regard to additional coil embolization, Kulcsar et al.[ 12 ] suggested that the addition of coils prevents rapid thrombosis and unstable thrombus formation, resulting in the prevention of delayed aneurysm rupture. On the contrary, in a computational fluid dynamics study, Hassan et al.[ 8 ] reported that additional FD placement raises the intra-aneurysmal pressure and jet blood flow occurs. Therefore, they stated that the situation could lead to delayed rupture of the aneurysm. In the clinical setting, Hou et al.[ 9 ] reported that 38.7% of patients with delayed aneurysm rupture had multiple FD implants. Although additional FD implantation promotes thrombosis and increases the rate of complete embolization,[ 10 ] it is still unclear whether it lowers the incidence of delayed aneurysm rupture. In this case, the aneurysm was located at the extradural segment; therefore, we did not perform coil embolization. We believe that coil embolization should be considered before the FRED placement if jet blood flow is observed, due to the difficulty in placing a microcatheter in the aneurysm using the transcell technique, due to the small cell size.

The patient developed oculomotor palsy after sinus-packing. Zhang et al.[ 20 ] recently described that 2.4% of the patients who received sinus-packing for dural arteriovenous fistulas of the cavernous sinus suffer from transient oculomotor dysfunction. In addition, Schaaf et al.[ 19 ] noted that coil embolization of the aneurysm itself, rather than sinus packing, improved 96% of cases, including the diplopia that was present preoperatively. Considering these reports, the occurrence of oculomotor nerve palsy within this treatment series was relatively low. Additional coil embolization, including sinus-packing after delayed aneurysm rupture, was considered acceptable.


We reported a case of delayed aneurysm rupture that occurred after FRED implantation to alert surgeons about the possibility of this complication. The number of cases of FRED implantation is expected to increase in the future due to its ease of use and extended indications. However, even if FRED implantation is safer and the rupture rate of its aneurysm is lower than other options, delayed aneurysm rupture might still occur, as shown in this case. Careful follow-up, such as platelet aggregation evaluation and preoperative consideration on whether to add coil embolization, may help to prevent the development of delayed aneurysm rupture for patients treated with a FRED. However, it should be noted that the main limitation of this study is that only a single case was reported, and thus a mechanism could not be determined; therefore, further studies with more cases are needed.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest


The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.


1. Brinjikji W, Murad MH, Lanzino G, Cloft HJ, Kallmes DF. Endovascular treatment of intracranial aneurysms with flow diverters: A meta-analysis. Stroke. 2013. 44: 442-7

2. Chalouhi N, Tjoumakaris SI, Gonzalez LF, Hasan D, Pema PJ, Gould G. Spontaneous delayed migration/shortening of the pipeline embolization device: Report of 5 cases. AJNR Am J Neuroradiol. 2013. 34: 2326-30

3. Chow M, McDougall C, O’Kelly C, Ashforth R, Johnson E, Fiorella D. Delayed spontaneous rupture of a posterior inferior cerebellar artery aneurysm following treatment with flow diversion: A clinicopathologic study. AJNR Am J Neuroradiol. 2012. 33: E46-51

4. Fischer S, Vajda Z, Perez MA, Schmid E, Hopf N, Bazner H. Pipeline embolization device (PED) for neurovascular reconstruction: Initial experience in the treatment of 101 intracranial aneurysms and dissections. Neuroradiology. 2012. 54: 369-82

5. Griessenauer CJ, Mohlenbruch MA, Hendrix P, Ulfert C, Islak C, Sonnberger M. The FRED for cerebral aneurysms of the posterior circulation: A subgroup analysis of the EuFRED registry. AJNR Am J Neuroradiol. 2020. 41: 658-62

6. Hanel RA, Cortez GM, Lopes DK, Nelson PK, Siddiqui AH, Jabbour P. Prospective study on embolization of intracranial aneurysms with the pipeline device (PREMIER study): 3-year results with the application of a flow diverter specific occlusion classification. J Neurointerv Surg. 2022. 0: 1-8 online ahead of print

7. Hanel RA, Kallmes DF, Lopes DK, Nelson PK, Siddiqui A, Jabbour P. Prospective study on embolization of intracranial aneurysms with the pipeline device: The PREMIER study 1 year results. J Neurointerv Surg. 2020. 12: 62-6

8. Hassan T, Ahmed YM, Hassan AA. The adverse effects of flow-diverter stent-like devices on the flow pattern of saccular intracranial aneurysm models: Computational fluid dynamics study. Acta Neurochir (Wien). 2011. 153: 1633-40

9. Hou K, Li G, Lv X, Xu B, Xu K, Yu J. Delayed rupture of intracranial aneurysms after placement of intra-luminal flow diverter. Neuroradiol J. 2020. 33: 451-64

10. Ikeda H, Ishii A, Kikuchi T, Ando M, Chihara H, Arai D. Delayed aneurysm rupture due to residual blood flow at the inflow zone of the intracranial paraclinoid internal carotid aneurysm treated with the pipeline embolization device: Histopathological investigation. Interv Neuroradiol. 2015. 21: 674-83

11. Killer-Oberpfalzer M, Kocer N, Griessenauer CJ, Janssen H, Engelhorn T, Holtmannspotter M. European multicenter study for the evaluation of a dual-layer flow-diverting stent for treatment of wide-neck intracranial aneurysms: The European flow-redirection intraluminal device study. AJNR Am J Neuroradiol. 2018. 39: 841-7

12. Kulcsar Z, Houdart E, Bonafe A, Parker G, Millar J, Goddard AJ. Intra-aneurysmal thrombosis as a possible cause of delayed aneurysm rupture after flow-diversion treatment. AJNR Am J Neuroradiol. 2011. 32: 20-5

13. Luecking H, Engelhorn T, Lang S, Goelitz P, Kloska S, Roessler K. FRED flow diverter: A study on safety and efficacy in a consecutive group of 50 patients. AJNR Am J Neuroradiol. 2017. 38: 596-602

14. McDougall CG, Diaz O, Boulos A, Siddiqui AH, Caplan J, Fifi JT. Safety and efficacy results of the flow redirection endoluminal device (FRED) stent system in the treatment of intracranial aneurysms: US pivotal trial. J Neurointerv Surg. 2022. 14: 577-84

15. Piano M, Valvassori L, Lozupone E, Pero G, Quilici L, Boccardi E. FRED Italian registry: A multicenter experience with the flow re-direction endoluminal device for intracranial aneurysms. J Neurosurg. 2019. p. 1-8

16. Pierot L, Spelle L, Berge J, Januel AC, Herbreteau D, Aggour M. Feasibility, complications, morbidity, and mortality results at 6 months for aneurysm treatment with the flow re-direction endoluminal device: Report of SAFE study. J Neurointerv Surg. 2018. 10: 765-70

17. Pierot L, Spelle L, Berge J, Januel AC, Herbreteau D, Aggour M. SAFE study (safety and efficacy analysis of FRED embolic device in aneurysm treatment): 1-year clinical and anatomical results. J Neurointerv Surg. 2019. 11: 184-9

18. Rouchaud A, Brinjikji W, Lanzino G, Cloft HJ, Kadirvel R, Kallmes DF. Delayed hemorrhagic complications after flow diversion for intracranial aneurysms: A literature overview. Neuroradiology. 2016. 58: 171-7

19. Van der Schaaf IC, Brilstra EH, Buskens E, Rinkel GJ. Endovascular treatment of aneurysms in the cavernous sinus: A systematic review on balloon occlusion of the parent vessel and embolization with coils. Stroke. 2002. 33: 313-8

20. Zhang S, Wang J, Liu D, Lv M. Embolization of cavernous sinus dural arteriovenous fistula (CSDAVF) via transvenous approaches: Practice, experience summary and literature review. J Clin Neurosci. 2021. 89: 283-91

Leave a Reply

Your email address will not be published. Required fields are marked *