Embolic Materials in Middle Meningeal Artery Embolization for Chronic Subdural Hematoma

Abstract

Recurrence of chronic subdural hematoma (cSDH) has been suggested to involve angiogenesis and leakage from the fragile neovasculature within the outer membrane of the hematoma, which is primarily supplied by the distal branches of the middle meningeal artery. Middle meningeal artery embolization (MMAE) has recently gained recognition as an effective treatment, either as a standalone procedure or as an adjunct to burr-hole drainage, to reduce recurrence and reoperation rates. Various embolic materials are used in MMAE, including ethylene-vinyl alcohol copolymer (EVOH)-based agents (Onyx [Medtronic, Irvine, CA, USA], Squid [Balt, Montmorency, France]), polylactide-co-glycolide (PLGA) and polyhydroxyethyl methacrylate (HEMA)-based agent (PHIL; Terumo Neuro, Aliso Viejo, CA, USA), n-butyl cyanoacrylate (NBCA), particulates such as polyvinyl alcohol (PVA) and trisacryl gelatin microspheres (TGM), and coils. EVOH-based and PLGA-HEMA-based agents provide controlled deep distal penetration and durable occlusion, providing the strongest evidence in recent randomized controlled trials. NBCA enables rapid and cost-effective embolization but requires precise technique to prevent complications such as catheter entrapment. Particulates (PVA and TGM) are inexpensive and widely available, yet carry a higher recanalization risk and are often combined with coils or liquid embolics. Coils alone have limited efficacy, although they serve a protective role during liquid embolic injection. In Japan, NBCA is the predominant material, often combined with coils or particles, due to insurance coverage and guideline recommendations. Comparative evidence among embolic agents remains limited, highlighting the need for further studies to define optimal material selection and standardize MMAE strategies.

Introduction

The recurrence and progression of chronic subdural hematoma (cSDH) have been suggested to involve angiogenesis and leakage from fragile neovasculature within the outer membrane of the hematoma, which receives its primary supply from distal branches of the middle meningeal artery (MMA). Burr-hole drainage with irrigation and hematoma evacuation is the common procedure for cSDH treatment. In recent years, middle meningeal artery embolization (MMAE) has emerged as a therapeutic strategy designed to occlude this vascular supply. This approach has attracted increasing attention for its effectiveness in both initial treatment and reducing recurrence and the need for additional surgical interventions. Between 2024 and 2025, several randomized controlled trials (RCTs), including EMBOLISE, STEM, and MAGIC-MT, have reported favorable results supporting the efficacy of MMAE, which has contributed to its growing adoption, particularly outside Japan, as part of the standard treatment paradigm for cSDH.^1–5) A consensus statement by cSDH experts on disease management also identified MMAE as an adjunct to conventional surgical and nonsurgical management.⁶⁾ In these studies, systematic reviews, and case series, various embolic agents have been employed.^7,8) Liquid embolic agents include ethylene-vinyl alcohol copolymer (EVOH)-based materials (e.g., Onyx [Medtronic, Irvine, CA, USA], Squid [Balt, Montmorency, France]), poly(lactide-co-glycolide) (PLGA) and 2-hydroxyethyl methacrylate (HEMA)-based materials (PHIL; Terumo Neuro, Aliso Viejo, CA, USA), and adhesive agents include n-butyl cyanoacrylate (NBCA). Particulate materials, such as polyvinyl alcohol (PVA) particles and trisacryl gelatin microspheres (TGMs), the latter commonly marketed as Embosphere (Merit Medical, South Jordan, UT, USA) in Japan, have also been used, often in combination with coils. No definitive evidence currently supports the superiority of one embolic material over another, and the choice of agent varies across clinical studies. This review aimed to summarize and critically evaluate the current literature on embolic materials used in MMAE for the treatment of cSDH.

Characteristics of Each Embolic Material and Practical Points

In this section, we summarize the characteristics, advantages, and practical considerations of each embolic material used in MMAE (Table 1).

Table 1 Embolization materials of MMAE for cSDH

Embolic material	Main components	Product line-up	Approval status in Japan	Mechanism of embolization of vessels	Delivery method	Advantage/limitation
Onyx	EVOH copolymer dissolved in DMSO with tantalum powder	18, 20, 34 (viscosity grades, nominal cP)	Unapproved for MMAE (approved for AVM and DAVF)	Forms a cohesive spongy cast as DMSO diffuses, permanently occluding the vessel	Injected slowly via DMSO-compatible microcatheter	Nonadhesive, allows controlled, prolonged injection Good visibility due to tantalum Longer procedural time
Squid	EVOH copolymer dissolved in DMSO with micronized tantalum	12, 12 LD, 18, 18 LD, 34, 34 LD (viscosity grades, nominal cP)	Unapproved materials	Forms a cohesive spongy cast as DMSO diffuses, permanently occluding the vessel	Injected slowly via DMSO-compatible microcatheter	Lower viscosity versions available than Onyx (Squid 12, Squid 18) Smaller tantalum particles, less imaging artifact Longer procedural time
PHIL	Precipitating hydrophobic injectable liquid (polymer + iodine-based radiopacity) dissolved in DMSO	LD, 25%, 30%, 35% (polymer concentration, wt%)	Unapproved materials	Precipitates immediately upon contact with blood, forming a solid embolus	Injected via DMSO-compatible microcatheter	No tantalum, reduced imaging artifact on postop CT/MRI Faster precipitation than Onyx and Squid Slightly less control compared with Onyx/Squid
Histoacryl	N-butyl cyanoacrylate surgical glue	Single formulation; concentration adjustable by Lipiodol dilution	Approved for MMAE (approved for cerebral vessel embolization)	Polymerizes instantly upon contact with blood, forming a hard permanent cast	Mixed with Lipiodol for visibility and controlled polymerization, injected rapidly	Rapid, permanent occlusion, less control Inexpensive and widely available High risk of catheter entrapment
TRUFILL nBCA Liquid Embolic System	N-butyl cyanoacrylate surgical glue	Single formulation; concentration adjustable by Lipiodol dilution	Unapproved for MMAE (approved for AVM and DAVF)	Polymerizes instantly upon contact with blood, forming a hard permanent cast	Mixed with Lipiodol for visibility and controlled polymerization, injected rapidly	Rapid, permanent occlusion, less control Inexpensive and widely available High risk of catheter entrapment
PVA	Polyvinyl alcohol particles (various calibrated sizes, e.g., 150–250 μm)	Commonly used in MMAE with particle size 150–250 μm	Unapproved materials	Physically occludes small arterioles by lodging in distal branches	Injected suspended in contrast solution (minimum compatible microcatheter ID ≥0.021″)	Cost-effective Effective for distal occlusion Not permanent (risk of recanalization) Larger microcatheter (depending on particle size)
Embosphere	Spherical trisacryl gelatin microspheres (calibrated size, e.g., 100–300 μm)	Commonly used in MMAE with particle size 300–500 μm	Unapproved for MMAE (approved for hypervascular tumors and AVM)	Flow-directed lodging in distal vasculature, causing mechanical occlusion	Injected suspended in contrast solution (minimum compatible microcatheter ID ≥0.021″)	More uniform size than PVA → predictable penetration Smoother injection, less aggregation Larger microcatheter (depending on microsphere size)
Coil	Platinum or stainless steel	Various diameters and lengths	Available (indications unclear)	Induces thrombosis by slowing flow and providing a scaffold for clot formation	Deployed via microcatheter under fluoroscopy	Precise, immediate proximal occlusion, no distal penetration Useful to block the main MMA trunk Prevent reflux of liquid embolic

AVM, arteriovenous malformation; cP, centipoise; cSDH, chronic subdural hematoma; DAVF, dural arteriovenous fistula; DMSO, dimethyl sulfoxide; Embosphere, Merit Medical, South Jordan, UT, USA; EVOH, ethylene-vinyl alcohol; Histoacryl, B. Braun, Melsungen, Germany; ID, inner diameter; LD, low density; MMA, middle meningeal artery; MMAE, middle meningeal artery embolization; Onyx, Medtronic, Irvine, CA, USA; PHIL, Terumo Neuro, Aliso Viejo, CA, USA; PVA, polyvinyl alcohol; Squid, Balt, Montmorency, France; TRUFILL, Johnson & Johnson, Irvine, CA, USA

EVOH-based liquid embolic materials (Onyx, Squid)

EVOH-based agents are nonadhesive, and this characteristic enables controlled slow injection, which facilitates deep penetration into the distal branches of the hematoma outer membrane and achieves durable occlusion. This property makes them particularly suitable for complete distal filling of tortuous or multiple outer membrane branches. Onyx (Medtronic) achieves radiopacity by suspending tantalum powder in the EVOH–dimethyl sulfoxide (EVOH–DMSO) solution, whereas Squid (Balt) employs micronized tantalum powder, which provides improved homogeneity of radiopacity and reduced sedimentation, allowing more consistent fluoroscopic visualization during prolonged injections. Onyx is available in different viscosity grades expressed in centipoise (18, 20, 34), and Squid offers an even wider range (12, 18, 34, and 34 low viscosity [LV]). This diversity of formulations allows operators to adjust the balance between distal penetration and proximal plug formation according to procedural requirements.⁹⁾ RCTs and meta-analyses on MMAE have primarily used EVOH agents as standard materials, providing the strongest body of evidence for clinical efficacy.^1–3) Key technical considerations include the use of DMSO-compatible microcatheters and the necessity of slow injection to minimize DMSO-related pain and vascular spasm. Endovascular procedures using Onyx are generally recommended under general anesthesia in Japan, although local anesthesia and conscious sedation were also allowed in these RCTs. Notably, 6.2%–20.9% of embolization procedures were performed using local anesthesia.^1,2) Operators must carefully avoid reflux or inadvertent embolization through high-risk anastomoses such as the ophthalmic artery, branches of the internal carotid artery, superficial temporal artery, or skin branches.^10,11) Catheter entrapment in external carotid artery branches is rare, yet close attention to catheter positioning remains essential. EVOH agents are more costly than other embolic agents, but they are particularly indicated for recurrent cases or when distal filling of multiple tortuous outer membrane branches is required, as reflected in the STEM and EMBOLISE trials.

PLGA-HEMA-based liquid embolic material (PHIL)

PHIL (Terumo Neuro) is a precipitating, nonadhesive liquid embolic agent composed of a copolymer of PLGA and HEMA, dissolved in DMSO. For radiopacity under fluoroscopic guidance, iodine is covalently bound to the polymer backbone, eliminating the need for suspended radiopaque particles and thus preventing sedimentation or the need for agitation. The device obtained Conformité Européenne (CE) marking in July 2014. PHIL is provided in formulations defined by polymer concentration (25%, 30%, 35% by weight).

Adhesive liquid embolic materials (Histoacryl, TRUFILL nBCA Liquid Embolic System)

Cyanoacrylate, in its monomeric state, is a low-viscosity liquid that polymerizes and hardens upon contact with trace amounts of anions, forming a polymeric adhesive bond. NBCA, whose polymerized form is odorless, nontoxic, and chemically stable, has been employed worldwide as a medical-grade tissue adhesive since the 1980s. The mechanism of vascular embolization by NBCA is thought to involve 3 processes: formation of a cast-like hardened polymer, thrombus formation, and adhesion to the vascular wall accompanied by endothelial injury. Histoacryl (B. Braun, Melsungen, Germany), composed primarily of NBCA, was approved in Japan as a tissue adhesive for skin closure. In 2013, it was additionally approved as an endoscopic embolic material for the treatment of gastric varices. Clinical application of NBCA for cerebral arteriovenous malformations (AVMs) began in the 1980s. Subsequently, in 2022, Histoacryl obtained regulatory approval in Japan for intravascular embolization, including both neurovascular and peripheral vascular indications. A similar medical device, the TRUFILL nBCA Liquid Embolic System (Johnson & Johnson, Irvine, CA, USA), was approved by the U.S. Food and Drug Administration in 2000 for embolization of cerebral AVMs as a preoperative adjunct to surgical resection and was subsequently approved in Japan in 2024 for the treatment of intracranial AVMs and dural arteriovenous fistulas.

Regarding the injection technique, the penetration distance can be controlled by adjusting the dilution rate with lipiodol. For MMAE, low-concentration mixtures are often used to achieve more distal penetration.^12–14) However, the adhesive nature of NBCA poses a risk of microcatheter entrapment. Because injection is brief, with limited opportunity for adjustment, accurate assessment of dangerous anastomoses and precise catheter positioning are critical. Comparative studies have suggested efficacy similar to that of EVOH in selected cases. Currently, NBCA is the only embolic material approved for MMAE in Japan, and many reports from Japan describe embolization performed with NBCA.^13–15)

Particulate embolic materials (PVA, TGM)

Particulate agents offer advantages in both availability and cost. PVA (particle size 150–250 μm) and Embosphere (Merit Medical; 300–500 μm) are most commonly reported in MMAE studies, and adjusting particle size enables modulation of proximal-to-distal penetration.¹⁶⁾ However, recanalization may occur due to proximal occlusion or collateral flow, and the risk of inadvertent embolization of the ophthalmic branches must be considered. In clinical practice, combining particles with coils or liquid embolics reduces these risks, but comparative studies show no superiority over particles alone or coils alone.^17–19) Many reports have described the use of PVA in combination with MMAE, yet to date, randomized evidence remains scarce, with EMPROTECT representing the only such trial available.^20,21)

Coils

Coils primarily serve an adjunctive role because they are costly and have limited embolization effects on the thin blood vessels of the outer membrane. When used alone, coils may permit residual flow in distal outer membrane branches, thereby reducing their effectiveness in preventing recurrence. They are typically deployed for trunk protection (to prevent reflux) or proximal flow control, and they are commonly combined with liquid or particulate embolics to optimize occlusion.

Embolic Materials in RCTs and Previous Studies of MMA Embolization for cSDH

Table 2 shows the summary of the results and embolic materials used in several RCTs and other clinical studies conducted internationally.^{1–3,21–25)} The EMBOLISE trial evaluated the addition of MMAE using Onyx (Medtronic) to standard surgical treatment in a surgical cohort. The study demonstrated a significant reduction in treatment failure within 90 days, defined as recurrence requiring reoperation or functional deterioration. The authors also reported that the safety profile of adjunctive MMAE was within acceptable limits. The MAGIC-MT trial, a China-led RCT, examined non-acute subdural hematomas and specifically centered on the use of Onyx. This trial confirmed the added benefits of MMAE when combined with conventional management. The STEM trial investigated Squid (Balt) and reported a lower treatment failure rate than standard care alone. The EMPROTECT trial, using 300–500 μm Embosphere (Merit Medical) for MMAE, did not significantly reduce 6-month recurrence compared with standard care, although both recurrence and reoperation rates were lower with MMAE. Systematic reviews and meta-analyses that integrated data from EMBOLISE, STEM, MAGIC-MT, EMPROTECT, and other studies consistently supported the efficacy of MMAE in reducing recurrence and the need for reoperation.^1–3,21) However, it should be noted that these studies differed in patient populations, embolic agents, and outcome measures, with embolic materials especially showing considerable variation reflecting historical changes in practice. Internationally, liquid embolic agents remain the most widely used, particularly EVOH-based materials such as Onyx, Squid, and PHIL (Terumo Neuro), as well as NBCA.²⁶⁾ Researchers have also reported the use of particulate embolic agents such as PVA particles and TGMs. Recent studies have favored EVOH-based materials for MMAE, whereas reports from the 2010s frequently described the use of particulate embolic materials.¹⁷⁾

Table 2 Study design and outcome of embolization for cSDH from overseas

Author (year)	Country	Embolization materials	Study design	Total number of patients (number of treatment groups)	Study population	Concomitant surgery with MMAE (%)	Post-embolization recurrence (%)	Complication related to MMAE (n (%))
Davies et al.1) (2024) (EMBOLISE)	USA	Onyx	Randomized controlled trial	400 (197)	Symptomatic subacute subdural hematoma or cSDH	100%	4.1% (within 90 days)	2 (1.0%)
Liu et al.3) (2024) (MAGIC-MT)	China	Onyx	Randomized controlled trial	722 (360)	Symptomatic non-acute subdural hematoma	78.1% (281/360)	6.7% (within 90 days)	Facial nerve paralysis (1, 0.3%); contrast agent allergy (2, 0.6%)
Fiorella et al.2) (2025) (STEM)	USA	Squid	Randomized controlled trial	310 (149)	Symptomatic cSDH	61.0% (91/149)	3% (within 180 days)	0 (0%)
Shotar et al.21) (2025) (EMPROTECT)	France	TGM (300–500 μm Embosphere)	Randomized controlled trial	308 (162)	Postoperative cSDH	100% (prior to MMAE)	14.8% (within 6 months)	MCA occlusion during MMAE (1, 0.6%)
Scoville et al.22) (2023)	USA	Onyx, NBCA, PVA, TGM	Retrospective case series	208 (208)	cSDH treated with MMAE in upfront, recurrent, and prophylactic settings	7.7% (16/208)	4.9%	Postsurgical infections (2, 1%); worsening headaches (2, 1%); new-onset seizures (2, 1%); MMA rupture (2, 1%); ECA spasm (2, 1%); postprocedural facial droop from Onyx infiltration (2, 1%); stroke due to subdural compression (1, 0.5%); others (5, 2.5%)
Krothapalli et al.23) (2023)	USA	Onyx, NBCA, PVA	Retrospective case series	116 (116)	cSDH treated with MMAE	41.4% (48/116)	1.7%	Ischemic stroke (1, 0.9%)
Kan et al.24) (2021)	USA	Onyx, NBCA, PVA, TGM, Coil	Retrospective case series	138 (138)	cSDH with primary treatment or recurrence after conventional surgery	0%	6.5%	Asymptomatic MMA rupture (1, 0.7%); postoperative seizure (1, 0.7%); facial droop (1, 0.7%)
Joyce et al.25) (2020)	USA	Onyx, NBCA, PVA, TGM, Coil	Retrospective case series	121 (121)	Non-acute subdural hematoma treated with MMAE in upfront, recurrent, and prophylactic settings	11.3% of treatments (17/151)	6.0%	Intermittent aphasia (1, 0.8%); delayed seizure (1, 0.8%); delayed infarction (1, 0.8%)

cSDH, chronic subdural hematoma; ECA, external carotid artery; Embosphere, Merit Medical, South Jordan, UT, USA; MCA, middle cerebral artery; MMA, middle meningeal artery; MMAE, middle meningeal artery embolization; NBCA, n-butyl cyanoacrylate; Onyx, Medtronic, Irvine, CA, USA; PVA, polyvinyl alcohol; Squid, Balt, Montmorency, France; TGM, trisacryl gelatin microspheres

Several scoping reviews and comparative studies have highlighted key differences between embolic materials.^5,7,16,17) Liquid embolic agents achieve superior distal penetration into the fragile neovasculature of the outer membrane of the hematoma and provide more durable occlusion. By contrast, particulate agents are prone to recanalization, although they remain widely used because of lower cost and greater availability. Because a variety of embolic materials and combination strategies have been employed, identifying the optimal treatment remains difficult. Recent systematic reviews and meta-analyses have demonstrated no clear differences in efficacy between liquid embolic agents and particulate materials and have likewise found no superiority among different liquid agents such as Onyx, Squid, and NBCA.^7,16,27,28) In addition, Kan et al. reported no significant differences in the reduction of subdural hematoma thickness across coils, liquid agents, particles, and coil combinations with either liquid or particle agents.²⁴⁾

Review of Japanese Studies on Embolic Materials for cSDH

Table 3 shows the summary of the results and embolic materials used in several clinical studies in Japan. A nationwide survey by Murai et al. investigated the current status of MMAE for cSDH in Japan between 2018 and 2022, including 466 patients treated at 40 centers.²⁹⁾ The number of MMAE procedures increased steadily over 5 years, reflecting growing recognition of this technique, particularly for recurrent cases. Regarding embolic materials, the study demonstrated a clear preference for NBCA. Approximately half of all procedures (50.0%) used NBCA alone, making it the most common material. In some cases, NBCA was combined with particles or coils to achieve more complete vessel occlusion. Particle embolization alone accounted for a smaller proportion of cases (15.8%), whereas coil-only embolization was rare (2.8%). Overall, most operators favored liquid embolics because of their ability to penetrate distal MMA branches and fragile neovascular networks within the hematoma membrane. The variety of material combinations likely reflects individualized approaches based on vascular anatomy and technical considerations. Institutional reports further support the efficacy of NBCA, either alone or in combination with coils, demonstrating reduced recurrence rates through targeted occlusion of distal branches supplying the outer membrane of the hematoma.^{13–15,30,31)} Other case series have also reported successful embolization using PVA particles or TGM.³²⁾ Regarding regulatory status, Onyx (Medtronic) has been approved in Japan since 2008; however, its use was initially limited to preoperative embolization of brain AVMs. In 2018, the indication was expanded to include dural arteriovenous fistulas that are difficult to treat effectively with transvenous embolization or other approaches. However, coverage has not been extended to MMAE. NBCA has received broader insurance approval for head and neck applications, and numerous reports have described its clinical use in MMAE. Other EVOH-based agents, such as PHIL (Terumo Neuro) and Squid (Balt), remain unapproved and unavailable for clinical practice in Japan. TGM is marketed in Japan as Embosphere (Merit Medical) and has been approved by the Medical Devices Department as a prosthetic material to promote embolization in blood vessels of the central circulatory system. However, the approved intended use is restricted to arterial embolization therapy for patients with hypervascular tumors or AVMs, without specific approval for cSDH. PVA has not received device approval in Japan, which makes its use as an embolic material for MMAE in cases of cSDH difficult. Consequently, Japanese practitioners primarily use NBCA and coils, sometimes in combination, whereas Onyx is employed only off-label in selected cases.

Table 3 Study design and outcome of embolization for cSDH in Japan

Author (year)	Embolization materials	Study design	Total number of patients (number of treatment groups)	Study population	Concomitant surgery with MMAE (%)	Post-embolization recurrence (%)	Complication related to MMAE (n (%))
Nakagawa et al.13) (2019)	NBCA	Retrospective case series	402 (20)	Recurrent cSDH after ≥2 prior burr-hole surgeries	100% (after MMAE)	0.0%	0 (0%)
Yajima et al.30) (2020)	NBCA	Retrospective case series	18 (18)	Symptomatic cSDH	88.9% (16/18)	0.0%	0 (0%)
Dofuku et al.31) (2023)	NBCA	Retrospective case series	9 (9)	Recurrent cSDH after burr-hole surgery	100% (prior to MMAE)	0.0%	0 (0%)
Okuma et al.15) (2019)	NBCA (n = 11), TGM (n = 3), Coil (n = 1), NBCA+TGM (n = 2)	Retrospective case series	17 (17)	cSDH with ≥2 risk factors for intractability	88.2% (15/17)	0.0%	0 (0%)
Saito et al.14) (2019)	NBCA (n = 7), NBCA+PVA (n = 1)	Retrospective case series	8 (8)	cSDH with ≥2 recurrences within 3 months or high risk of recurrence	87.5% (7/8)	12.5%	0 (0%)
Izawa et al.32) (2019)	PVA (n = 3), TGM (n = 8)	Retrospective case series	11 (11)	cSDH with organized recurrence after ≥2 prior surgeries	100% (prior to MMAE)	0.0%	Delayed wound healing (1, 9.1%)

cSDH, chronic subdural hematoma; MMAE, middle meningeal artery embolization; NBCA, n-butyl cyanoacrylate; NR, not reported; PVA, polyvinyl alcohol; TGM, trisacryl gelatin microspheres

Discussion

MMAE materials in current clinical trials and previous studies

With growing evidence from multiple RCTs, the clinical adoption of MMAE has expanded internationally. The embolic materials used in these RCTs, however, were limited, as each trial was sponsored by a company that provided both the embolic agents and research funding. Consequently, only a few comparative reports exist, and no randomized clinical trials have yet sought to determine the optimal embolic material for MMAE. Pulappadi et al. conducted a retrospective and prospective study examining MMAE embolic materials and reported that both PVA and TGM effectively prevented recurrence.³³⁾ However, distal penetration of TGMs did not provide an advantage over PVA particles. Shehabeldin et al. compared Onyx (Medtronic) and PVA and found no significant differences in embolization failure rates or the need for unplanned surgical evacuation. Hematoma thickness at late follow-up was significantly smaller in the PVA group.³⁴⁾ Smaller case series employing various embolic agents further complicate efforts to distinguish their individual effects.³⁵⁾ Even in the presence of strong RCT-based evidence for EVOH-based liquid embolic agents such as Onyx and Squid (Balt), this should not be interpreted as demonstrating their superiority over other embolic materials.

Experience and practice patterns of embolic materials in Japan

In Japan, Mandai et al. reported successful prevention of recurrence in cSDH cases with repeated recurrences using PVA for MMAE in 2000.³⁶⁾ Since then, several small-scale case series have been published, but no RCTs have been conducted. PVA has traditionally been used, while more recent reports describe increasing use of NBCA (Table 3). Reports support the safety and efficacy of NBCA in MMAE for cSDH,³⁷⁾ a particularly important issue, especially in Japan. A meta-analysis comparing embolic materials for MMAE found no significant differences in safety or effectiveness between NBCA, PVA, and Onyx, although concerns persist about the lack of procedural standardization.²⁷⁾ Results from ongoing clinical trials evaluating NBCA in MMAE, such as Middle Meningeal Artery Embolization for the Treatment of Subdural Hematomas With TRUFILL (Johnson & Johnson) n-BCA (MEMBRANE) and Efficacy of a Minimally Invasive Therapy Adjuvant to the Standards of Care by Cyanoacrylate Embolization (LEADH), are awaited.³⁸⁾ Although PVA is not approved for use in Japan, it was previously employed in various vascular embolization procedures at some facilities. However, PVA has recently become difficult to obtain and is now rarely used in clinical practice. Embosphere (Merit Medical) has received approval for the treatment of hypervascular brain tumors such as meningiomas but is not currently approved for MMAE.

Technical and procedural considerations and safety management for each material

Technical considerations and advantages of each embolic material are listed in Table 1. EVOH-based liquid embolic materials are nonadhesive and can be injected slowly, allowing wide embolization of tiny blood vessels in the outer membrane of the cSDH. By contrast, liquid embolic materials such as NBCA often depend on concentration and injection technique, requiring instantaneous judgment and substantial operator experience to achieve stable delivery. Al-Mufti et al. reported that in MMAE performed with a 1:6 diluted mixture of NBCA and ethiodized oil, distal penetration improved when a bolus of 5% dextrose was administered through the guide catheter.^12,39) The concentration of NBCA must be adjusted according to catheter reach, and successful treatment relies on targeting the cSDH membrane supplied by neovasculature from the MMA while achieving maximal penetration.^14,40) Embosphere may reach small distal vessels, yet the minimum size is 100–300 μm, which limits the ability to embolize the entire outer membrane vessel. Delivery also requires a relatively large-caliber microcatheter, making distal navigation in the tortuous MMA challenging. Although coils are considered the safest embolic option, they provide only a limited embolic effect and are not regarded as the material of first choice. Regardless of the embolic material selected, dangerous anastomoses must be considered, including connections to the ophthalmic/internal carotid branches, vertebral artery, and petrosal branches, when embolizing from branches of the external carotid artery. A thorough understanding of the vascular anatomy is essential before surgery, and embolization should be performed only within a safe range. Potential complications include cerebral infarction (caused by pial embolization or thrombosis), ocular injury, skin necrosis, and DMSO-related pain. RCTs and meta-analyses have reported low rates of serious adverse events when strict procedural guidelines are followed. Regarding other procedural aspects, during MMAE for cSDH using liquid embolic materials, conscious sedation or general anesthesia is commonly used. The choice between conscious sedation and general anesthesia seems to have little effect on treatment outcomes or adverse events.⁴¹⁾

Economic considerations and future directions

In the United States, the number of patients with cSDH is projected to increase markedly, with approximately 60000 new cases expected annually. Healthcare expenditures for treatment are estimated to reach nearly 2 billion US dollars by 2030. Similarly,⁴²⁾ in Japan, the increasing proportion of medical expenses within the national budget reflects demographic pressures, particularly an elderly population. The economic impact of increasing MMAE utilization has also been examined. A report evaluating the cost of recurrence prevention and the addition of MMAE found that the reduction in recurrence balanced the total medical expenses associated with the procedure.⁴³⁾ In this study, a relatively inexpensive Embosphere was used. However, wider adoption of more costly liquid embolic materials, such as Onyx, in the future could increase total medical expenditures.

Conclusion

MMAE is an effective treatment for cSDH that reduces recurrence and the need for reoperation. EVOH-based liquid agents such as Onyx (Medtronic) and Squid (Balt) provide the strongest evidence, owing to their deep penetration and durable occlusion; however, this should not be interpreted as definitive proof of their superiority over other embolic materials. In Japan, NBCA is most commonly used because of its availability, although it requires careful technique. Particles and coils serve primarily as adjuncts. Future studies should clarify the optimal embolic strategy and contribute to standardizing treatment approaches.

Declarations

Funding

This review article received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Authors’ contributions

Dr. KS contributed to the design of the review and drafting of the manuscript. Drs. SH, KF, ST, SF, HS, and HW contributed to critical revision of the manuscript for important intellectual content.

Disclosure statement

Kazutaka Sumita received lecture fees from Stryker and Medtronic. The other authors have no potential conflict of interest.

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