2024 middle meningeal artery embolization trials: A comprehensive review of past, recent, and ongoing trials

Abstract

Background and objectives

Middle meningeal artery embolization (MMAE) has become a pivotal intervention in managing chronic subdural hematomas (cSDHs). This systematic review synthesizes past, recent, and ongoing clinical trials to assess MMAE's role in cSDH treatment.

Methods

A systematic review was conducted using PRISMA guidelines, incorporating PubMed, ClinicalTrials.gov, and reverse bibliography searches to identify clinical trials evaluating MMAE for cSDH. Inclusion criteria included randomized and nonrandomized trials reporting outcomes, such as recurrence rates and procedural safety. Case reports, retrospective reviews, and opinion pieces were excluded.

Results

Seven published and 15 ongoing trials were identified. Landmark randomized controlled trials (RCTs), including EMBOLISE, STEM, and MAGIC-MT, demonstrated reductions in hematoma recurrence and surgical rescues with MMAE, establishing its role as both an adjunctive and standalone therapy. Ongoing trials, such as EMPROTECT and CHESS, investigate diverse embolic agents, procedural strategies, and patient populations to optimize MMAE outcomes. However, challenges remain, including variability in patient selection criteria, embolic materials, and endpoints.

Conclusion

MMAE is an innovative and minimally invasive approach that has reshaped cSDH management. Evidence supports its efficacy and safety as an adjunct to surgery and a potential standalone therapy for select patients. Future research should focus on long-term outcomes, subgroup analyses, and standardization of protocols to further refine its application and integration into clinical practice.

Introduction

Chronic subdural hematoma (cSDH) is a common condition among elderly patients, and carries significant morbidity, mortality, and recurrence risks. ¹ Traditional management involves burr-hole drainage and craniotomy, but although it is associated with high recurrence rates and often necessitates additional interventions. Middle meningeal artery embolization (MMAE) has emerged as a promising adjunctive therapy for cSDH. By targeting the arterial supply contributing to inflammation, angiogenesis, and recurrent bleeding in the dural layer, MMAE treats the underlying pathophysiology of cSDH and reduces recurrence rates. Initial retrospective studies demonstrated the feasibility and safety of MMAE, generating interest in its broader clinical application.

2024 marks a pivotal moment in the evolution of MMAE with the publication of results from three landmark randomized controlled trials—EMBOLISE, STEM, and MAGIC-MT—in the New England Journal of Medicine (Figure 1). EMBOLISE and STEM provided robust evidence supporting the efficacy of reducing hematoma recurrence.^2,3 All three demonstrated the safety of MMAE in reducing adverse complications, sparking widespread interest in this treatment modality. Given the recent and ongoing advancements for this treatment modality, there is a need for a resource that provides a “snapshot” of the current landscape of both published and ongoing MMAE trials and their efficacy in cSDH treatment. Thus, this review aims to provide an updated and comprehensive overview of all clinical trials supporting MMAE, recent clinical breakthroughs, and ongoing research efforts to refine its role in managing cSDH.

Figure 1.

Timeline of notable MMAE studies.

Methods

The study adhered to PRISMA guidelines for systematic reviews, which do not require a protocol or registration and thus were not conducted (Figure 2). PubMed and Google Scholar were utilized to identify studies published in any language evaluating MMAE for cSDH. Keywords included “middle meningeal artery embolization,” “chronic subdural hematoma,” and “MMA embolization.” Reverse bibliography searches were performed on all included studies to ensure comprehensive coverage. Additionally, ClinicalTrials.gov and meeting abstracts were reviewed to identify ongoing trials.

Figure 2.

PRISMA flowchart.

Inclusion criteria consisted of randomized or nonrandomized trials evaluating MMAE for cSDH. Studies that provided data on adjunctive treatment status, embolic agent type, and procedural outcomes were included. Human studies that were case reports, letters of editorial opinion, or retrospective studies were excluded.

Screening was conducted using Rayyan (Rayyan Systems Inc.). Three reviewers (AAG, AN, JYC) independently screened titles and abstracts. Conflicts were resolved through open discussion with all three reviewers. Full-text articles meeting inclusion criteria were extracted using a predefined data table in Microsoft Excel (Microsoft Corporation, Redmond, WA). For each trial, we documented the trial name, start date, short name or abbreviation, principal investigator(s), clinical trial registration number, funding source, trial status, eligibility criteria regarding hematoma size, trial arms and interventions, embolic agents used, primary and secondary endpoints, enrollment targets, and the number of patients per arm.

A meta-analysis was not performed due to ongoing discussions among study investigators of trials such as EMBOLISE and STEM regarding pooled data analyses, which would provide a significantly higher level of evidence than we would be able to provide. ⁴ In 2015, a pivotal meta-analysis of individual patient data from five randomized trials demonstrated the efficacy of EVT, leading to a paradigm shift in guidelines. ⁵ These findings, published in The Lancet, demonstrated the impact of high-quality pooled analyses.^5–9 Instead, a qualitative review was conducted to synthesize findings from the available literature. All extracted data are available upon reasonable request to the corresponding author.

Results

Seven published and 15 ongoing trials were identified as of November 26^th, 2024.

Published trials

Seven published trials evaluating MMAE for cSDH were identified, representing a range of study designs, patient populations, and interventions (Table 1). Most are from the United States, although there were trials such as that led by Ng et al. from Montpellier, France, and another (MAGIC-MT) from Shanghai, China.^10,11 Across these trials, MMAE consistently demonstrated a favorable impact on hematoma recurrence, surgical rescue rates, and functional outcomes.

Table 1.

Overview of key trials on middle meningeal artery embolization for chronic subdural hematoma.

Name	Month	Year	Short name	First author	Last author	Journal	Clinical trial number	Funding source	Hematoma size	Trial arms/intervention	Embolic agent used	Primary endpoint	Secondary endpoint	Number of patients	Patients per arm	Key findings
Embolization of the Middle Meningeal Artery for Chronic Subdural Hematoma	Nov.	2024	EMBOLISE	Jason M. Davies	Adnan H. Siddiqui	NEJM	NCT04402632	Medtronic	Max 15 mm or midline shift >5 mm	Embolization + Surgery Surgery	Onyx	Hematoma recurrence and/or surgical rescue within 90 days.	Non-inferiority assessment, readmission, radiographic features	400	197 embo + surg 203 surg	Primary outcome event occurred in 4.1% of embo group, 11.3% in control (RR, 0.36; 95% CI, 0.11–0.80; p = 0.008).
Adjunctive Middle Meningeal Artery Embolization for Subdural Hematoma	Nov.	2024	STEM	David Fiorella	Adam S. Arthur	NEJM	NCT04410146	Balt USA	>10 mm size	Surgical stratum: Embolization + surgery Surgery standalone Non-surgical stratum: Embolization standalone Medical management	SQUID	Hematoma recurrence and/or surgical rescue within 180 days.	180 day mRS	310	Surgical stratum: 91 embo + surg 98 surg Non-surgical stratum: 58 embo only 63 medical management	Surgical stratum: Primary outcome occurred in 14% of the embo + surg group, while 23% in the surg group (OR, 0.60; 95% CI, 0.27–1.35). Non-surgical stratum: Primary outcome occurred in 19% of the embo group, while 56% in the mm group (OR, 0.19; 95% CI, 0.08–0.46). No significant difference in mortality between embolization and the control for either strata.
Middle Meningeal Artery Embolization for Nonacute Subdural Hematoma	Nov.	2024	MAGIC-MT	Jianmin Liu	Ying Mao	NEJM	NCT04700345	Shanghai Shenkang Hospital Development Center and others	Excluded patients warranting craniotomy	Embolization + medical management vs. medical management (excluded patients undergoing craniotomy)	Onyx	Symptomatic recurrence or progression within 90 days	Clinical and imaging outcomes	722	360 embolization, 362 usual treatment (78.3% of all patients got burr hole drainage, most were after embo)	Symptomatic recurrence or progression was less likely in embo group (-3.3%, -7.4 to 0.8, p = 0.10). Incidence of serious adverse effects decreased in embo group (6.7% vs 11.6%, p = 0.02)
Middle meningeal artery embolization following surgical evacuation of symptomatic chronic subdural hematoma improves outcomes, interim results of a prospective randomized trial	Oct.	2024	–	Luca Debs	Scott Rahimi	JNIS	NCT04272996	Augusta University	>10 mm size, >5 mm midline shift	Embolization + surgery vs. Surgery	Onyx	Hematoma recurrence within 180 days	embolic complications	35	17 embo + surg 18 surg only	Neurological improvement upon discharge in 71% of embo + surg and 56% of surg groups (p = 0.29). Embo + surg group maintained neurological improvements while deteriorating in surg group during follow-up (71% vs 33%*; NNT, 2.5; RR, 0.44; p = 0.03). 7 (39%) surg required reintervention, while it was needed in only 1 (6%) embo + surg (NNT, 3.0; RR, 0.15; p = 0.15).
The efficacy of postoperative middle meningeal artery embolization on chronic subdural hematoma—A multicentered randomized controlled trial	May	2023	–	Alexander Lam	Peter Mews	Surgical Neurology International	ACTRN12621000263897p	Life Health Care Group	Mean preoperative thickness was 21.2 mm vs 20.9 mm in embo and monitoring groups, respectively (p = 0.969)	Evacuation + surgery vs. Surgery	SQUID, Onyx, Phil 25%, n-BCA	Symptomatic recurrence with repeat surgical evacuation	mRS, complications, and maximal thickness of residual cSDH at 6 weeks and 3 months	35	16 evacuation + embo 19 evacuation + monitoring	No recurrence was found in embolized patients compared to 3 patients without embo who needed repeat surgery (P = 0.234). No significant difference in residual hematoma thickness. Patients with embolization had lower mRS compared to non-embolized patients (P = 0.018)
Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: A Series of 60 Cases	Nov.	2018	–	Thomas Link	Jared Knopman	Neurosurgery	NCT03307395	Weill Medical College of Cornell University	–	Embolization vs. Embolization + surgery	Polyvinyl alcohol particles	Hematoma recurrence requiring surgical rescue	Procedure-related complications, neurological deficits and hematoma size reduced by >50%	60	42 embo only 8 embo for recurrent hematoma after prior surg 10 embo + surg	Of the 50 without prior surgical history, 45 had reported data. Within this 45, only 4 (8.9%) experienced a primary outcome and 41 (91.1%) improved clinically. 31 (68.9%) experienced a reduction in size >50%, and no neurological deficits were seen.
Middle meningeal artery embolization as an adjuvant treatment to surgery for symptomatic chronic subdural hematoma: a pilot study assessing hematoma volume resorption	July	2020	–	Sam Ng	Vincent Costalat	JNIS	–	None declared	65.2 ± 27.1 mL for embolization + surgery vs 51.2 ± 27.4 mL for surgery alone; p = 0.14	Embolization + surgery vs. Surgery	Polyvinyl alcohol particles	Hematoma volume resorption at 3 months	Recurrence of CSDH and safety measures at 3 months	41	19 embo + surg 22 surg alone	Mean difference in hematoma volume resorption was higher in embo + surg group versus surg alone by 17.5 mL (95% CI 3.87 to 31.16 mL)

The EMBOLISE trial demonstrated that adjunctive MMAE with Onyx (Medtronic) significantly reduced 90-day recurrence rates compared to surgery alone, with recurrence observed in 4.1% of embolized patients versus 11.3% in the control group (p = 0.008). This trial highlighted the potential of MMAE to enhance surgical outcomes by addressing residual hematoma formation and improving radiographic resolution. The STEM trial demonstrated the efficacy of an alternative embolic agent, Squid (Balt USA), and similarly stratified patients into surgical and nonsurgical management cohorts. Among surgical patients, adjunctive embolization reached the primary efficacy outcome of recurrent cSDH with or without surgical rescue or major complications within 180 days (16% vs. 36%; OR = 0.36 (0.20–0.66); p = 0.001). Notably, MMAE demonstrated significant efficacy in nonsurgical patients, with a recurrence rate of 19% in the embolization group compared to 56% with medical management alone. The MAGIC-MT trial focused on patients managed medically, excluding those requiring craniotomy. Although the primary endpoint of symptomatic recurrence did not reach statistical significance (p = 0.10), serious adverse events were reduced in the embolization group (6.7% vs. 11.6%, p = 0.02).

A smaller trial by Debs et al. investigated MMAE following surgical evacuation of symptomatic cSDH. The addition of embolization was associated with sustained neurological improvement during follow-up (71% vs. 33%, p = 0.03) and a reduced need for reintervention (6% vs. 39%). Postoperative MMAE was also evaluated in a multicenter study, where embolized patients demonstrated improved functional outcomes with lower modified Rankin scale (mRS) scores (p = 0.018) and no recurrences, compared to three recurrences in the non-embolized group.

Ongoing trials

Fifteen ongoing or recently completed trials are actively investigating the role of MMAE in managing cSDH. These trials aim to further refine the role of MMAE in both surgical and nonsurgical contexts, address gaps in our knowledge of recurrence rates after MMAE, and expand upon our understanding of its impact on functional recovery and safety (Table 2).

Table 2.

Ongoing clinical trials pending per ClinicalTrials.gov.

Name	Start month	Start year	Short name	Principal investigator(s)	Clinical trial number	Funding source	Trial status	Hematoma size	Trial arms/intervention	Embolic agent used	Primary endpoint	Secondary Endpoint	Target enrollment	Patients per arm
Embolization of the Middle Meningeal Artery for the Prevention of Chronic Subdural Hematoma Recurrence in High Risk Patients	Oct.	2020	EMPROTECT	Eimad Shotar	NCT04372147	Assistance Publique-Hôpitaux de Paris	Completed*	>10 mm size, >5 mm midline shift	Embolization + surgery vs. Medical management	EmboSphere	Hematoma recurrence within 180 days	Repeated surgery, disability + dependency, mortality/complications, and hospital stay within 180 days	342	171 embo + surg 171 medical management
Swedish Trial on Embolization of Middle Meningeal Artery Versus Surgical Evacuation in Chronic Subdural Hematoma	Mar.	2022	SWEMMA	Mattias Drake Johan Wasselius	NCT05267184	Region Skane	Recruiting	Midline shift >10 mm	Embolization vs. Surgery	Onyx or Squid or Phil	Surgical rescue within 90 days	Neurological disability (mRS), quality of life (EQ-5D), and composite endpoint between 90 and 365 days, hematoma volume and procedure related complication rate within 90 days, and technical success rate within 24 h	288	144 embo alone 144 surg alone
Preventing Recurrences of Chronic Subdural Hematoma in Adult Patients by Middle Meningeal Artery Embolization	May	2022	MEMBRANE (Germany)	Alexander Hoenning	NCT05327933	Unfallkrankenhaus Berlin	Recruiting	–	Embolization + surgery vs. Surgery	Onyx or microelectric coils	Hematoma recurrence within 90 days	mRS and hematoma recurrence or intervention complication	154	77 embo + surg 77 surg alone
Middle Meningeal Artery Embolization for the Treatment of Subdural Hematomas With TRUFILL® n-BCA (MEMBRANE)	May	2021	MEMBRANE (USA)	Christopher Kellner, Ansaar Rai	NCT04816591	Cerenovus, Part of DePuy Synthes Products, Inc.	Active, not recruiting	–	Embolization vs. Surgery vs. Embolization + Surgery, vs. Medical Management	TRUFILL n-BCA	Hematoma recurrence within 180 days	Reduction of hematoma volume, change in mRS	376	Not available
Embolization of Middle Meningeal Artery in Chronic Subdural Hematoma	Dec.	2020	ELIMINATE	William Vandertop	NCT04511572	Academisch Medisch Centrum-Universiteit van Amsterdam	Recruiting	–	Embolization + surgery vs. Surgery	PVA particles	Surgical rescue for recurrent hematoma within 24 weeks	Hematoma volume reduction, mRS, complications, mNIHSS, MOCA, mortality, ADLs, short form health survey, iMCQ, EQ-5D-5L, productivity cost questionnaire, and Markwalder grading scale score within 24 weeks	170	Not available
Puerto Rico Embolization of the Middle Meningeal Artery for the Treatment of Chronic Subdural Hematoma Trial	Aug.	2024	PREMMA	Maria M Garcia Perez	NCT06466733	Juan M. Ramos Acevedo	Not yet recruiting	–	Embolization vs. Surgery	PVA particles	Reoperation at 3, 6, 12 months	mRS, GCS, VAS, EQ-5D-5L, radiological outcomes, technical success of embo, procedure-related complications, adverse effects, post-operative morbidity, mortality, length of stay	658	Not available
Endovascular vs Conservative Treatment in Patients With Chronic Subdural Hematomas and Mild Symptoms	Mar.	2024	n/a	Lucio Castellan	NCT06274580	Ospedale Policlinico San Martino	Not yet recruiting	<20 mm in width, <7 mm midline shift	Embolization standalone vs. Medical management	PVA particles	Incomplete (<50%) hematoma resolution or surgical rescue within 180 days	Treatment complication within 30 days or treatment success	300	Not available
Chronic Subdural Hematoma Treatment With Embolization Versus Surgery Study	Nov.	2024	CHESS	Peter Kan	NCT06347796	The University of Texas Medical Branch, Galveston	Recruiting	>10 mm in thickness if unilateral, >5 mm in thickness if bilateral	Embolization vs. Surgery	CONTOUR Embolization Particles device	Need for rescue surgery or death within 180–210 days of randomization	Proportion of subjects with symptomatic ischemic stroke, serious/life threatening adverse events, worsening of neurologicla status, or development of new disabling neurological symptoms, seizures, and/or cranial neuropathy within 180 days of randomization	520	Not available
Middle Meningeal Artery (MMA) Embolization Compared to Traditional Surgical Strategies to Treat Chronic Subdural Hematomas (cSDH)	June	2019	n/a	Angelica Fuentes	NCT04095819	Atlantic Health System	Unknown status	–	Embolization standalone Surgery standalone	PVA particles and n-BCA glue	Change in size of hematoma within 180 days	Changes in neurological status within 180 days	50	Not available
Middle Meningeal Artery Embolization for Chronic Subdural Hematomas	July	2024	STORMM	Aria Nouri	NCT06163547	University Hospital, Geneva	Not yet recruiting	–	Embolization + surgery vs. Surgery vs. Embolization vs. medical management	Not specified	Surgical reoperation, neurological deterioration due to cSDH after evacuation, post-operative hematomy volume of more than 90% of preoperative volume at follow-up at 6 months	GCS mRS, MGS, KPS, TDN grade, mortality rate, re-hospitalization at 6 months	180	Not available
The Onyx™ Trial For The Embolization Of The Middle Meningeal Artery For Chronic Subdural Hematoma	Oct.	2021	OTEMACS	Vincent Costalat	NCT04742920	University Hospital, Montpellier	Recruiting	>10 mm in thickness, unspecified midline shift	Embolization + surgery vs. Surgery	Onyx	Hematoma recurrence in embolism group vs standard of care group within 90 days, incidence of all cause mortality at 90 days	Mortality and major disabling stroke rates at discharge within 7 days, incidence of PRSAEs and DRSAEs in 24 hr, recurrence rate requiring surgery and hematoma volume change within 90 days, length of stay, mRS, EQ-5D-5L, Barthel Index.	440	Not available
Efficacy of a Minimally Invasive Therapy Adjuvant to the Standards of Care by Cyanoacrylate Embolization	Mar.	2023	LEADH	Jean-Christophe Gentric	NCT05374681	University Hospital, Brest	Recruiting	>10 mm in thickness	Embolization + surgery vs. Surgery vs. Embolization vs. medical management	n-BCA glue	CSH recurrence defined by the composite endpoint: A symptomatic CSH during the 6-month FU period A secondary surgical management during the 6-month FU period A remaining or reaccumulated hematoma on NCCT at 6 months	Number of symptomatic cSDH, secondary surgical management, remaining or reaccumulated hematoma, mortality rate, mRS, RACE score evaluation, quality of life, Barthel scale, success rate of embolization, complication rate of embolication, volumetry of CSH, maximum thickness of CSH, and rate of adverse effects at 6 months	550	Not available
Endovascular Embolization of Chronic Subdural Hematomas After Surgery	Feb.	2022	ENCLOSURE	Alejandro Tomasello	NCT05220826	Hospital Universitari Vall d'Hebron Research Institute	Unknown status	>10 mm in thickness with midline shift greater than 5 mm or neurological symptoms attributable to mass effect	Embolization + surgery vs. Surgery	Onyx, Phil, Squid, Libro	Recurrence of cSDH within 6 months	mRS, complications from embo, hematoma volume after treatment, and length of stay at 6 months	280	140 surgical drainage 140 surgical drainage + embo
Middle Meningeal Artery Embolization for Chronic Subdural Hematoma	Sep.	2019	n/a	Joshua Osbun	NCT04065113	Washington University School of Medicine	Recruiting	"Significant” midline shift	Embolization + surgery vs. Embolization vs. medical management	PVA particles	Hematoma recurrence or surgical rescue within 90 days	mNIHSS, mRS, procedure-related complication rate, and change in hematoma size within 90 days.	600	Not available
Management of CSDH With or Without EMMA- a Randomized Control Trial	Aug.	2021	EMMA-Can	Jai Shankar	NCT04750200	University of Manitoba	Recruiting	>10 mm in thickness and has one or more symptoms attributable to cSDH	Embolization + surgery vs. Surgery	PVA or EVOH	Recurrence of size of cSDH on CT scan of head within 90 days from embo	Peri-procedural morbidity and mortality related to embo, reduction of size of cSDH at 90 days from embo	200	Not available

Several trials, such as EMPROTECT and MEMBRANE, focus on whether adjunctive embolization reduces hematoma recurrence rates and improves long-term outcomes compared to surgery alone. For example, EMPROTECT assesses outcomes in patients with hematoma size >10 mm or midline shift >5 mm using EmboSphere particles. Similarly, the MEMBRANE trial from Berlin, Germany, evaluates adjunctive embolization with Onyx or microelectric coils, targeting recurrence within 90 days as the primary endpoint. ¹² Another trial also named MEMBRANE is ongoing and is based out of the United States, uses TRUFILL n-BCA (Cerenovus, Part of DePuy Synthes Products, Inc.). In preliminary results this trial has demonstrated MMAE significantly decreased failure rates in the treatment of cSDH when compared to the standard of care, with a common odds ratio (OR) of 0.529 (90% CI: 0.308–0.909) over 6 months. In the surgical cohort, failure rates were 8.5% for patients receiving MMAE versus 20.2% for those undergoing surgery alone (OR: 0.475). ¹³

Conversely, trials like CHESS and SWEMMA are examining MMAE as a standalone therapy. These studies aim to identify patient populations that may benefit from minimally invasive embolization as an alternative to surgical evacuation, particularly in cases of moderate hematoma burden or high surgical risk. Both trials focus on recurrence rates and functional outcomes, with SWEMMA also assessing procedural success rates and quality of life metrics.

Ongoing research includes a diverse array of embolic materials. While established agents such as Onyx and n-BCA remain widely used, trials like ELIMINATE and CHESS investigate alternative materials, including polyvinyl alcohol (PVA) particles and Contour particles (Boston Scientific) devices, to optimize procedural safety and efficacy. This reflects a growing interest in tailoring embolization techniques to specific patient needs and procedural goals. Although hematoma recurrence is the predominant primary endpoint across trials, secondary outcomes provide a broader understanding of MMAE's impact. Many studies incorporate functional status assessments, such as mRS scores and quality of life metrics (e.g. EQ-5D).

The inclusion criteria across trials reflect efforts to stratify patients based on hematoma characteristics and symptom severity. Trials such as ENCLOSURE focus on patients with significant hematoma burden or midline shifts, while others, such as PREMMA, aim to evaluate MMAE's role in less vulnerable patient populations. This variability underscores the importance of defining optimal patient selection criteria, particularly in differentiating between candidates for standalone embolization versus adjunctive approaches.

Discussion

The evolution of cSDH management has reached a pivotal moment with the advent of middle MMAE. Over the past few years, studies have established MMAE as a promising therapeutic modality. The recent publication of landmark trials, including EMBOLISE, STEM, and MAGIC-MT, has provided the highest evidence, demonstrating MMAE's potential to potentially significantly reduce recurrence rates and surgical rescues in adjunctive and standalone roles.^2,3,11

Current landscape of MMAE trials

These three trials mark a shift from feasibility and early-stage studies to large-scale, multicenter randomized controlled trials, offering robust insights into MMAE's efficacy and safety. EMBOLISE established that adjunctive MMAE significantly reduces hematoma recurrence and reoperation rates compared to surgery alone, and the results from a second observational cohort is set to be published soon. STEM demonstrated that MMAE reduces treatment failure in surgical and nonsurgical cohorts, validating its standalone efficacy in selected nonsurgical patients. Although not statistically significant, MAGIC-MT reinforced these findings by showing lower adverse event rates and a trend towards lower recurrence rates. When MMAE is combined with medical management, these findings reinforce the transformative impact of prior advancements in neurovascular care, such as the 2015 EVT trials, and position MMAE as a similarly groundbreaking innovation.

Despite these advances, understanding the trajectory of MMAE requires revisiting its origins and early evidence. MMAE was first used in a cSDH case report in 2000, where it was employed to manage a coagulopathic patient with spontaneous hematoma formation. ¹⁴ Over the decade, a few small single-center studies provided preliminary data on feasibility and safety, highlighting the potential efficacy of MMAE.^15–17 Between 2016 and 2018, there was a growing interest in MMAE which led to a proliferation of prospective and observational studies and meta-analyses, which began to establish its role in reducing hematoma recurrence.^10,18,19 However, these early studies faced significant limitations, including small sample sizes, heterogeneous techniques, and outcome variability, underscoring the need for rigorous randomized trials.^20–23 The first large multi-center study of consecutive MMAE was led by Kan et al. in 2019, demonstrating the efficacy of MMAE across 154 consecutive embolizations, which achieved a 97.4% technical success rate, and 70.8% of patients showed over a 50% imaging improvement. ²¹ Within the last few years, there has been a surge of prospective, multi-center studies that have corroborated these findings.^24–28

The three recent NEJM trials represent a significant advancement in the quality of evidence supporting MMAE, but critical questions persist. Patient selection criteria across these trials remain heterogeneous, particularly regarding frail or anticoagulated patients who might benefit most from MMAE but are frequently excluded from clinical studies. ²⁹ Single-center studies have shown that up to 39% of patients with cSDH are ineligible for trials due to radiographic features or comorbidities. ²⁹ Despite this, these studies reported 88.9% satisfactory hematoma resolution among trial-ineligible patients. Importantly, no significant differences between trial-ineligible and trial-eligible groups regarding surgical rescue rates or hematoma resolution outcomes were observed. ²⁹ Ogoing trials such as EMPROTECT are specifically addressing higher-risk populations, including those with chronic alcoholism or liver cirrhosis, further to evaluate MMAE's role in these vulnerable groups.

The variability in embolic agents, procedural timing, and study endpoints poses significant challenges to cross-trial comparisons in MMAE research. ³⁰ Some studies, such as EMPROTECT, focus narrowly on recurrence and reoperation rates, while others, like PREMMA, adopt a broader perspective by incorporating metrics such as quality of life, functional independence, and healthcare utilization. ³¹ This diversity highlights the evolving priorities in evaluating MMAE, reflecting clinical and patient-centered outcomes. Efforts to standardize procedural techniques and optimize embolic agent selection are central to advancing the field. The usage of other agents, including Contour PVA particles (Boston Scientific) and EmboSphere (MeritMedical), aims to improve safety profiles and procedural efficacy while reducing outcome variability.

Recent trials also emphasize the need for comprehensive patient centric endpoints beyond technical success. Evaluations of neurological outcomes, long-term functional recovery, and cost-effectiveness are gaining prominence, reflecting the multifaceted impact of MMAE on patient care. These ongoing trials are poised to provide critical evidence on the efficacy, safety, and cost-effectiveness of MMAE. By addressing variability in embolic agents, procedural strategies, and patient populations, these studies are expected to clarify the role of embolic agents in MMAE for cSDH management, and guide future standardization efforts.^32–34 By integrating these broader measures, ongoing studies strive to balance clinical effectiveness with considerations of quality of life and healthcare resource utilization, ultimately enhancing the relevance and applicability of MMAE findings to diverse patient populations and clinical settings.

Future directions

The evidence base for MMAE is now highly compelling, but it is not without limitations. While the three landmark NEJM trials provided high-quality data, long-term outcomes still need to be explored. Most studies focus on short- to medium-term endpoints, leaving questions about the durability of MMAE and its impact on long-term functional outcomes needing to be answered. Additionally, the underrepresentation of specific patient populations, such as those with significant comorbidities or bleeding diatheses, limits the generalizability of current findings. However, current single- and multi-center studies have demonstrated strong efficacy among these patients, and ongoing trials such as EMPROTECT are continuing to answer these questions.^35–38

MMAE is now firmly established as a valuable adjunct to surgery, particularly for reducing recurrence and reoperation rates in high-risk patients. It is also emerging as a standalone option for selected nonsurgical candidates, offering a less invasive alternative to traditional approaches. The challenge lies in tailoring MMAE strategies to individual patient profiles, considering factors such as hematoma size, symptom severity, and comorbidities to maximize therapeutic benefit. As ongoing trials refine its indications, MMAE is poised to become a cornerstone of cSDH management, reshaping treatment paradigms and improving outcomes for this complex and heterogeneous condition.

Conclusion

The recent advancements in MMAE have solidified its position as a transformative intervention in cSDH management. The recent landmark trials, including EMBOLISE, STEM, and MAGIC-MT, have provided evidence supporting MMAE's efficacy and safety, establishing it as a valuable adjunct to surgical evacuation and a promising standalone treatment for selected patients. These findings mark a pivotal moment in the evolution of cSDH treatment, shifting the paradigm from traditional surgical approaches to a more nuanced, minimally invasive strategy. Despite the substantial progress, challenges remain, including variability in patient selection criteria, procedural techniques, and outcome measures. Ongoing trials aim to address these gaps by exploring innovative embolic agents, optimizing procedural timing, and broadening the scope of MMAE's application in diverse patient populations. Future research must prioritize subgroup analyses, long-term outcome studies, and comparative trials to refine MMAE's role further and ensure its integration into standardized care protocols. As the evidence base grows, MMAE is poised to redefine cSDH treatment, offering improved outcomes and a path forward for high-risk and nonsurgical patients.

Abbreviations

MMAE

middle meningeal artery embolization

cSDH

chronic subdural hematoma

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

mRS

modified Rankin scale

PVA

polyvinyl alcohol

n-BCA

N-butyl cyanoacrylate adhesive

EQ-5D

EuroQol-5 dimensions

EMPROTECT

Embolization of the Middle Meningeal Artery for the Prevention of Chronic Subdural Hematoma Recurrence in High Risk Patients

STEM

Adjunctive Middle Meningeal Artery Embolization for Subdural Hematoma

MAGIC-MT

Middle Meningeal Artery Embolization for Nonacute Subdural Hematoma

MEMBRANE (Germany)

Preventing Recurrences of Chronic Subdural Hematoma in Adult Patients by Middle Meningeal Artery Embolization

MEMBRANE (USA)

Middle Meningeal Artery Embolization for the Treatment of Subdural Hematomas with TRUFILL^® n-BCA

CHESS

Chronic Subdural Hematoma Treatment With Embolization Versus Surgery Study

SWEMMA

Swedish Trial on Embolization of Middle Meningeal Artery Versus Surgical Evacuation in Chronic Subdural Hematoma

ELIMINATE

Embolization of Middle Meningeal Artery in Chronic Subdural Hematoma

PREMMA

Puerto Rico Embolization of the Middle Meningeal Artery for the Treatment of Chronic Subdural Hematoma Trial

STORMM

Middle Meningeal Artery Embolization for Chronic Subdural Hematomas

OTEMACS

The Onyx™ Trial for the Embolization of the Middle Meningeal Artery for Chronic Subdural Hematoma

LEADH

Efficacy of a Minimally Invasive Therapy Adjuvant to the Standards of Care by Cyanoacrylate Embolization

ENCLOSURE

Endovascular Embolization of Chronic Subdural Hematomas After Surgery

EMMA-Can

Management of CSDH With or Without EMMA – a Randomized Control Trial.