Delayed Migration of Onyx Embolic Agent after Preoperative Embolization of an Arteriovenous Malformation in a Pediatric Patient: A Case Report and Review of the Literature

• Brain arteriovenous malformations are frequently treated with Onyx liquid embolic agent (Onyx, Medtronic, Inc.).

• Delayed, unexpected Onyx migration is not well documented and is extremely rare in pediatric patients.

• The clinical presentation associated with delayed, unexpected Onyx migration is not well understood.

• A pediatric patient developed headaches and perinidal edema following preoperative AVM embolization, which was the result of delayed, unexpected Onyx migration. Concerns of possible venous outflow obstruction and hemorrhage prompted urgent surgical resection of the AVM.

• Migration of Onyx may occur in a delayed fashion following embolization, with the potential to cause dangerous complications.

• Sudden development of headaches and other signs of perilesional edema should prompt repeat angiographic examination due to the possibility of delayed liquid embolic migration.

• Future research is needed to understand the frequency of delayed Onyx migration from brain AVMs and the possible clinical presentations to look for.

Arteriovenous malformations (AVMs) are caused by arteriovenous shunting of coiled and tortuous vascular connections that connect feeding arteries to draining veins [1]. Although microsurgical resection remains the gold standard for treatment of all accessible pediatric AVMs, embolization and radiosurgery are often considered as adjunctive therapy [1]. Onyx liquid embolic agent (Onyx, Medtronic, Inc., Irvine, CA) is a non-adhesive embolic material approved for preoperative embolization of brain AVMs. In this report, we describe a pediatric patient who developed headaches and perinidal edema following preoperative AVM embolization. Ultimately, delayed migration of Onyx occurred following the procedure, which resulted in venous outflow obstruction and prompted urgent surgical resection of the AVM. We conducted a thorough literature review to investigate how common delayed Onyx migration associated with brain AVMs is thought to be in both adult and pediatric populations.

An 8-year-old female patient was referred to our institution upon experiencing daily frontal headaches with photophobia, phonophobia, and sleep disturbance. She had a history of seizures as a neonate. She also had a history of hypoxic ischemic injury, neurogenic bladder, right-sided hemiplegia, and anxiety. At the time of admission, she was taking Topamax (Janssen Pharmaceuticals, Beerse, Belgium) (25 mg) nightly for daily headaches, which had since become milder and less frequent. Informed consent was obtained from the patient’s legal guardian for the publication of this case report and accompanying images.

Cerebral angiography and MRI revealed an unruptured Spetzler-Martin grade III (S1E1V1; less than 3 cm, dentate nucleus involved, deep venous drainage) (Figs. 1, 2) AVM of the medial left cerebellar hemisphere with a high-flow shunt. The nidus was predominantly compact, measuring 19.6 × 19.1 × 23.4 mm (anteroposterior, transverse, craniocaudal). Arterial supply was from a hypertrophied left superior cerebellar artery. Three mildly dilated venous outlets were observed draining into the vein of Galen, the torcula, and the left transverse sinus/sigmoid/sinus junction, with no significant venous stasis or outflow stenosis observed.

Treatment was recommended based on the patient's young age, lesion location, and headaches. The AVM was preoperatively embolized using the plug and push technique, with a combination of Onyx 34 and Onyx 18 to reduce the nidus size before surgical resection. In this method, the catheter was first filled with Onyx 34 and then switched to Onyx 18 to allow the more viscous Onyx 34 to come out first and form a plug to support the forward egress of Onyx 18. We did not observe any procedural errors or complications during the procedure. Approximately 25% of the AVM nidus was closed during the embolization, specifically the deep posteroinferior aspect (Fig. 2). Further injection of Onyx was stopped once minimal penetration of Onyx into the main draining vein was noted, along with some reflux of Onyx along the microcatheter tip. The draining vein remained widely patent without flow delay or visible evidence of an Onyx cast obstruction. No attempt was made to close a significantly greater percentage of the AVM nidus in a single session due to the risk of precipitating a nidal rupture from excessive hemodynamic changes.

The following day, the patient developed worsening headaches, and an MRI demonstrated new perinidal edema (Fig. 3). Urgent angiography showed that Onyx had migrated into the draining vein, presumably resulting in venous outflow obstruction and potentially increasing the risk of bleeding from the AVM. Uneventful, urgent resection of the AVM was performed. Postoperative CT imaging (Fig. 4) revealed postoperative pneumocephalus, and a thin linear object with a hyperdensity compatible with Onyx material was seen extending posteriorly from the resection cavity. The object appeared to extend within or along the margin of the left transverse and sigmoid sinuses to the level of the jugular bulb.

The procedure was deemed successful as the patient recovered from surgery without any new neurological deficit, and there was no residual filling of the AVM on intra-operative angiography. At 1 month follow-up, she was at her neurological baseline. Magnetic resonance imaging and magnetic resonance angiography have been recommended 1 year after surgery; the timing of follow-up angiograms will be based on the MRI findings.

This case report describes a pediatric patient with an unexpected delayed migration of Onyx following preoperative embolization for an intracranial AVM. This case serves to alert neurovascular surgeons to vigilantly monitor for liquid embolic migration in a delayed fashion following an AVM embolization. Delayed migration of Onyx following embolization of an AVM is rarely reported in the literature [2]. Shetty and Miett [2] suggest that Onyx migration following embolization for brain AVMs is often asymptomatic in clinical presentation, although it could also present with hypoxemia and superior vena cava syndrome.

Our usual practice is to perform open surgical resection 24–48 h following preoperative embolization. Most AVMs undergo a single embolization session. At the end of the first session, if additional AVM pedicles remain that are deemed readily amenable to embolization, and if the multidisciplinary team feels further embolization would make surgery safer, then further embolization may be used prior to surgery. One of the issues that led to surgery in this case was the concern for occlusion of the draining vein resulting in the potential for impending rupture. Preoperative embolization with Onyx can reduce the amount of intra-operative bleeding during AVM resection by gradually reducing flow and preventing abrupt hemodynamic changes in arterial pressure [3]. However, overall rates of peri-operative hemorrhagic complications are estimated to occur in up to 16.7% of AVMs following embolic embolization with Onyx, due to reasons such as vessel perforation, catheter adhesion, draining vein occlusion, pressure changes, and vessel rupture [4].

Onyx is an ethylene vinyl-alcohol copolymer, which has very unique properties compared to n-butyl cyanoacrylate (nBCA). Cyanoacrylate glues are liquid monomers that form flexible polymers with strong adhesive bonds to soft tissues [5]. When using nBCA, it is important to remove the microcatheter as quickly as possible after injection, to prevent it from becoming glued into the blood vessel and left in place [6]. We are unaware of instances of delayed nBCA migration, which would not be expected given its glue-like properties. Onyx, on the other hand, has a lava-like flow. It takes longer to set and is therefore widely preferred as it affords greater control and time to complete the embolization. While it is still possible for the microcatheter to become stuck when using Onyx, the Onyx cast sticks to itself rather than the blood vessel. Multiple reports of Onyx migration are reported and described below; this is likely related to its fundamentally unique properties.

A review of the literature on delayed postoperative Onyx migration is presented in Table 1. Wang et al. [7] reported unintended Onyx migration into the middle inner ear 6 years following embolization of a right temporal AVM. Crusio et al. [8] documented Onyx migration into a right atrium stent 2 weeks after embolization of the right meningeal artery for a dural AVM. Several cases of delayed Onyx migration have also been reported in patients with dural arteriovenous fistulas (DAVFs). Shi et al. [9] reported Onyx migration in four patients with dural AVFs; one patient with a transverse sigmoid sinus DAVF who underwent a venous balloon-assisted procedure experienced a pulmonary embolism 1 month after surgery due to Onyx migration into the lung. Lv et al. [10] documented Onyx migration to the heart in two patients following embolization of the middle meningeal artery for DAVFs in the transverse sigmoid sinus; one patient sustained a mild tricuspid valve dysfunction 9 months following embolization. Shetty and Miett [2] reported an Onyx migration in a DAVF patient 3 months after embolic repair to the lower lobe branches of the right pulmonary artery. Singla et al. [11] reported a spontaneous Onyx extrusion through the scalp 5 weeks after embolization of the distal left occipital artery for a Borden type 3 DAVF. Watanabe et al. [12] also documented Onyx extrusion through the scalp 2 months after embolization through the left superficial temporal artery for a superior sagittal sinus DAVF. Finally, Wang et al. [7] documented a patient with a left tentorial DAVF who died during a surgical procedure; it was noted that Onyx migration occluded the distal draining vein and may have led to venous varix rupture.

Liquid embolic migration in pediatric patients has only been alluded to in one study in our review of the literature. Thiex et al. [13] analyzed clinical records of 15 pediatric patients who underwent 36 transarterial embolizations with Onyx for central nervous system arteriovenous lesions. They noted that, in two patients with a vein of Galen malformation, high shunt flow inadvertently carried a tiny stream of Onyx into the venous side of the lesion during the operation. In one of these patients, a thin strand of Onyx extended to within the midline varix of the media vein, remaining attached to the cast on the arterial side without detachment. This patient showed no change in vital signs or clinical signs of distal embolization. In another case, two drops of Onyx were rapidly carried through the venous pouch to the jugular bulb while the patient was undergoing embolization via a branch of the right lenticulostriate artery. The Onyx lodged in the jugular bulb without impeding flow, with no evidence of jugular stenosis. The oxygen saturation and vital signs remained stable and unchanged throughout the procedure.

This report provides evidence that migration of Onyx liquid embolic agent may occur in a delayed fashion following embolization, with the potential to cause dangerous complications. The sudden development of headaches and other signs of perilesional edema should prompt repeat angiographic examination due to the possibility of delayed liquid embolic migration. Furthermore, our report highlights the fact that more work needs to be done to understand the frequency of delayed Onyx migration from brain AVMs and the possible clinical presentations to look for.

The authors acknowledge Superior Medical Experts for research and drafting assistance.

Ethical approval is not required for this study in accordance with local or national guidelines. Informed consent for publication was obtained from the patient's legal guardian for the publication of this case report and accompanying images.

Tiffany Yesavage is employed by Superior Medical Experts. The authors report no conflict of interest concerning the materials or methods used in this manuscript.

This work was supported by a grant from the United Hospital Foundation.

Bailey Nussbaum, Patrick Graupman, Collin Torok, and Eric Nussbaum were responsible for the conception and design of this study and the interpretation and analysis of data. Tiffany Yesavage performed the literature review and drafted the manuscript. All authors critically revised the manuscript and approved the final version to be published.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.