Therapeutic Outcomes of Middle Meningeal Artery Embolization for Chronic Subdural Hematoma

Abstract

Chronic subdural hematoma (CSDH) is becoming increasingly common in the aging population, and preventing its recurrence after standard surgical drainage remains a significant clinical challenge. Middle meningeal artery embolization (MMAE) has emerged as a promising therapeutic option to interrupt the supply of neovessels to the outer membrane, thereby halting the cycle of inflammation and rebleeding. This review summarizes the latest findings on the therapeutic outcomes of MMAE, with a particular focus on 3 major randomized controlled trials reported in 2024: the STEM, EMBOLISE, and MAGIC-MT trials. Although these studies collectively suggest that MMAE can reduce the risk of treatment failure and recurrence, the results vary in terms of efficacy across different patient populations and study designs. The EMBOLISE trial demonstrated a significant reduction in recurrence requiring reoperation, whereas other trials adopted broader outcome definitions, which may partly explain the heterogeneity in reported efficacy. Consequently, MMAE may not be suitable for universal adoption across all patient populations. The procedure has a favorable safety profile and a low complication rate. Technical factors influencing success include the use of liquid embolic agents for distal penetration and the potential benefits of the transradial approach in reducing postoperative delirium in older patients. In conclusion, although MMAE is a valuable addition to CSDH management, a comprehensive evaluation is essential to optimize clinical outcomes.

Introduction

With the progression of an aging society, the incidence of chronic subdural hematoma (CSDH) is increasing along with the aging of the patient population itself. Given the frequent poor clinical outcomes observed in older patients, CSDH should no longer be considered a “benign disease.”¹⁾ While surgical drainage remains a widely used, simple, and effective standard of care for CSDH, the postoperative recurrence rate is 2%–37%,²⁾ making recurrence prevention a significant challenge. Middle meningeal artery embolization (MMAE) has recently attracted attention as an alternative therapeutic option to address this issue. The addition of MMAE to standard treatments has the potential to reduce the recurrence rate of CSDH.³⁾

The pathophysiology of CSDH is understood to be a process in which repeated microhemorrhages triggered by minor trauma induce an inflammatory cascade, leading to the formation of an outer membrane rich in fragile and leaky neovessels.⁴⁾ These neovessels receive blood supply primarily from the dural arterial system, including the middle meningeal artery (MMA); continuous microhemorrhage from the outer membrane is the primary cause of hematoma enlargement and recurrence.⁴⁾ Therefore, the primary mechanism of action of MMAE involves interrupting the vicious cycle of inflammation and rebleeding by blocking blood flow to the outer membrane, thereby promoting hematoma reduction and resolution via natural resorption mechanisms.⁵⁾ In 2024, 3 large-scale randomized controlled trials (RCTs) were reported^3,6,7) that rapidly accumulated evidence regarding the efficacy and safety of MMAE for CSDH. Here, the latest findings regarding the therapeutic outcomes of MMAE for CSDH are reviewed.

Therapeutic Objectives and Indications for MMAE

The therapeutic objectives of MMAE are classified into 2 categories, based on the timing of the procedure.

• 1.  Prevention of recurrence after standard treatment (adjunctive MMAE)
• 2.  Monotherapy for patients with asymptomatic or mild CSDH (standalone MMAE)

Adjunctive MMAE is performed in conjunction with standard treatment. For instance, when combined with surgical evacuation, MMAE suppresses neovascularization of the CSDH outer membrane while relieving the physical compression by the hematoma. This combination has been suggested to reduce the rates of recurrence, retreatment, and rehospitalization within 30 days compared with surgical evacuation alone.⁸⁾ However, standard treatment can sometimes include medical therapies such as statin therapy, requiring careful interpretation of evidence.

Standalone MMAE targets patients with asymptomatic or mildly symptomatic CSDH. In this group, the reported rates were 86.7% for hematoma resolution, 6.3% for recurrence, and 9.6% for retreatment.⁹⁾ While this demonstrates a certain level of effectiveness for standalone MMAE, it also suggests that hematoma enlargement or neurological deterioration may occur in some cases, highlighting the importance of careful patient selection and postprocedural follow-up.

Therapeutic Outcomes

Evidence regarding the efficacy and safety of MMAE has advanced significantly, with 3 RCTs conducted by 2024.^3,6,7) These trials suggest that adding MMAE as an adjunctive therapy to standard treatment (standard treatment includes conservative management in addition to surgery) can reduce the risk of treatment failure. Based on this, the Society of Vascular and Interventional Neurology (SVIN) has positioned the addition of MMAE to standard treatment for initial symptomatic CSDH as a Class I recommendation.⁴⁾ However, because of the differences in study designs, before adding MMAE to standard treatment for CSDH, careful interpretation must be performed (Table 1).

Table 1 Comparison of the MAGIC-MT, STEM, and EMBOLISE trials

	MAGIC-MT	STEM	EMBOLISE
Patients	Symptomatic nonacute SDH with mass effect	Symptomatic CSDH	Symptomatic subacute or chronic SDH requiring surgical evacuation
Treatment groups	Standard treatment (surgical or nonsurgical) vs. standard treatment plus MMAE	Standard treatment (surgical or nonsurgical) vs. standard treatment plus MMAE	Surgical drainage alone vs. surgical drainage plus MMAE
Embolic agent	Onyx	SQUID	Onyx
Primary outcome	Symptomatic recurrence or progression (90 days)	Residual or reaccumulation of the SDH (≥10 mm), surgical rescue, any new major disabling stroke after enrollment, MI, or death from any neurological cause (180 days)	Hematoma recurrence or progression requiring repeat surgery (90 days)
Results	9.9% (standard) vs. 6.7% (plus MMAE)	36.4% (standard) vs. 15.8% (plus MMAE)*	11.3% (surgery alone) vs. 4.1% (surgery + MMAE)*
Nonsurgical patients	21.8% (standard) vs. 8.9% (plus MMAE)*	55.8% (standard) vs. 18.8% (plus MMAE)*	Not reported
Surgical patients	6.7% (standard) vs. 6.0% (plus MMAE)	23.4% (standard) vs. 13.9% (plus MMAE)	11.3% (surgery alone) vs. 4.1% (surgery + MMAE)*

*Statistically significant (based on reported p values when available; otherwise, on 95% CIs excluding unity).

CI, confidence interval; CSDH, chronic subdural hematoma; MI, myocardial infarction; MMAE, middle meningeal artery embolization; SDH, subdural hematoma

The STEM trial³⁾ compared a standard treatment alone with a standard treatment plus MMAE using Squid in 310 patients with CSDH. The incidence of the primary endpoint at 180 days was 15.8% in the MMAE group and 36.4% in the control group, indicating that MMAE significantly suppressed treatment failure (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.20–0.65). This primary endpoint was a composite outcome comprising residual or re-accumulation of the SDH (≥10 mm), surgical rescue, or any new major disabling stroke, myocardial infarction, or death from neurological causes. Subgroup analysis showed a clear efficacy in the nonsurgical patients (18.8% vs. 55.8%; OR, 0.19; 95% CI, 0.08–0.46), whereas in surgical patients, although there was a trend toward improvement (13.9% vs. 23.4%; OR, 0.59; 95% CI, 0.26–1.35), the difference was not statistically significant.

The EMBOLISE trial⁶⁾ targeted 400 patients with CSDH eligible for surgical evacuation and compared surgery alone with surgery combined with MMAE using Onyx. The rate of hematoma recurrence requiring reoperation at 90 days was 11.3% in the surgery-alone group compared to 4.1% in the MMAE group, a significant reduction of approximately one-third (relative risk, 0.36). This trial demonstrates the efficacy of MMAE in suppressing recurrence after surgical treatment.

The MAGIC-MT trial⁷⁾ was the largest study to compare an MMAE combination group with a standard treatment group of 722 patients with CSDH. The frequency of symptomatic recurrence or progression at 90 days was 6.7% in the MMAE group and 9.9% in the standard treatment group; however, this difference was not statistically significant (p = 0.10). Although it was an exploratory subgroup analysis, efficacy was suggested in nonsurgical patients (8.9% vs. 21.8%), whereas there was negligible difference in surgical patients (6.0% vs. 6.7%). Thus, the efficacy of combination therapy with surgical treatment was not supported.

When interpreting the 3 RCTs, considering the proportion of surgical versus nonsurgical management as well as the between-trial differences is important in the content and consistency of “standard treatment.” Whereas EMBOLISE enrolled only surgically managed patients, the proportions managed surgically were 78.3% and 61.0% in MAGIC-MT and STEM, respectively.^3,6,7) In STEM, the incremental benefit of MMAE appeared larger in the nonsurgical stratum (absolute difference, 37%) than that in the surgical stratum (absolute difference, 9%),³⁾ suggesting that the case mix could materially influence the overall estimated treatment effect.

In addition, standard treatment was not identical across trials. In STEM, surgical management included burr-hole drainage and the Subdural Evacuating Port System,³⁾ reflecting procedural heterogeneity. In MAGIC-MT, statins and glucocorticoids were co-administered in 97.9% of patients,⁷⁾ whereas glucocorticoid use was restricted by protocol in EMBOLISE.⁶⁾ Although robust evidence for the recurrence-preventive effects of these co-interventions remains limited, such differences could have influenced control group event rates (recurrence or reoperation) and, consequently, the apparent magnitude and precision of any incremental benefit from MMAE. Notably, when baseline event rates are low, the absolute benefit of an add-on therapy is small, complicating detection.

Taken together, current data do not allow a definitive conclusion that MMAE, particularly adjunctive MMAE after surgical drainage, is uniformly effective across all CSDH populations. Only EMBOLISE clearly demonstrated reduced recurrence after surgical treatment, whereas postoperative recurrence rates varied widely across trials.^3,6,7) This discrepancy may be partly explained by differences in trial design. First, EMBOLISE was explicitly designed to evaluate postoperative recurrence prevention with adequate power. In contrast, STEM and MAGIC-MT evaluated surgical patients as a stratum/subgroup and may have been underpowered to detect a moderate benefit, particularly in STEM.^3,6,7) Second, the primary endpoint differed: EMBOLISE used repeat surgery for recurrent/progressive hematoma, whereas STEM used a composite endpoint that included radiographic components and non-hematoma events, potentially diluting sensitivity for postoperative recurrence prevention.^3,6) Third, MAGIC-MT had a low control group event rate, yielding a small absolute risk difference.⁷⁾ Differences in baseline patient characteristics and hematoma profiles may also have contributed to between-trial heterogeneity in observed treatment effects.

Given this variability in evidence, we performed “tailored treatment,” which involved stratifying retreatment risk based on hematoma volume and characteristics at presentation and adding MMAE only for the high-risk group.¹⁰⁾ Specifically, adding MMAE to the group with a high retreatment rate of 28.1% significantly reduced the rate to 3.2% (p = 0.01). Conversely, in the low-risk group, the retreatment rate remained low (0%–9.5%) from the outset, suggesting that the benefit of adding MMAE was relatively small. These results suggest that a strategy targeting MMAE in patients with high retreatment risk is rational.

When determining therapeutic indications, evidence regarding safety and factors associated with treatment failure must be considered. These aspects are detailed in the following sections.

Complications and Safety

The overall complication rate associated with MMAE is generally low. In a nationwide survey in Japan,¹¹⁾ the complication rate was 5.2% (24/462 cases), and the morbidity rate at 30 days due to complications was extremely low (0.9%). In the 3 previously mentioned RCTs,^3,6,7) the safety of the procedure was emphasized, with a low rate of treatment-related complications (≤2.0%). Taken together, these data suggest that MMAE is an acceptable therapeutic option in terms of perioperative safety. However, although uncommon, clinically significant procedure-related adverse events were reported, including stroke with functional impairment in EMBOLISE⁷⁾ and facial nerve palsy in MAGIC-MT.³⁾ In addition, domestic surveys have reported visual impairment as well as stroke.¹¹⁾ Such complications may arise from unintended embolization through dangerous anastomoses to the internal carotid or ophthalmic circulation, or from reflux of the embolic agent into proximal branches (e.g., branches supplying cranial nerves). Accordingly, to minimize embolization of dangerous channels (e.g., dural–pial anastomoses, meningo-ophthalmic arteries, and squamopetrosal branch), careful microcatheter positioning (distal [superior] to the anterior clinoid process on lateral projection) and, when feasible, selective embolization of the frontal and/or parietal branch of the MMA are recommended.⁴⁾ Given that such severe complications can occur, albeit infrequently, operators should recognize these risks and obtain thorough informed consent from patients. The major complications based on the literature are summarized in Table 2.

Table 2 Procedure-related complications in MMAE: Japanese registry and randomized trials*

Data source/study	Outcome/adverse event	Frequency (%)	Key clinical notes
Japan registry11)	30-day morbidity attributable to complications	0.9
	MMA-MMV shunt	2.4	Most are asymptomatic and can be observed
	Intracranial hemorrhage	0.6	Unclear
	Cerebral ischemia/infarction	0.6	Thromboembolism related to catheter manipulation or migration of embolic material
	Visual impairment/blindness	0.4	Risk of irreversible blindness due to migration of embolic material into anastomotic branches between the MMA and the ophthalmic artery (e.g., recurrent meningeal artery)
	Puncture site complications	0.4	Hematoma, pseudoaneurysm, etc.
MAGIC-MT3)	Embolization-related complications	0.8
	Facial nerve palsy	0.2
	Contrast media allergy	0.6
STEM6)	Serious procedure-related complications	0
EMBOLISE7)	Serious adverse events	2.0
	Disabling stroke	1.0	Catheter manipulation, atherosclerosis

*Event definitions and follow-up windows differed across studies; thus, direct cross-study comparisons should be interpreted with caution.

MMA, middle meningeal artery; MMAE, middle meningeal artery embolization; MMV, middle meningeal vein

Predictors of Treatment Success/Failure

Clinical and imaging factors

• •  Number of recurrences¹¹⁾: Cases with a history of 2 or more burr-hole surgeries have a significantly higher risk of recurrence after MMAE. The efficacy of MMAE is limited in refractory cases.
• •  Use of antithrombotics: While studies found no direct association between antithrombotics and MMAE failure, others have reported higher retreatment rates with the use of anticoagulants, such as Xa inhibitors.^12,13)
• •  Small MMA diameter (<1.5 mm)¹²⁾: A small MMA diameter is an independent predictor of requiring reoperation (OR 1.1–5.7). A more likely explanation might be an additional arterial supply to the CSDH membrane, such as from the occipital artery or accessory MMA, and contralateral dural arterial supply. Moreover, a narrow vessel diameter makes microcatheter navigation difficult and may prevent the embolic agent from sufficiently reaching the distal capsular network (prone to proximal occlusion).

Procedural factors

• •  Embolic agents: The SVIN consensus guidelines classify the use of liquid embolic agents in MMAE as Class I.⁴⁾ Liquid agents are widely used because of their high penetrability into the distal vessels,¹⁴⁾ and all 3 RCTs introduced previously used liquid embolic agents.^3,6,7) Other coils and particles remained in Class IIb because of insufficient evidence. However, no head-to-head comparative evidence exists across embolic materials; thus, the availability of randomized evidence using ethylene vinyl alcohol-based liquid agents (e.g., Onyx and Squid) should not be interpreted as proof of superiority of these agents over other materials.
• •  Embolization technique: Some reports have suggested the usefulness of occluding all convexity branches.¹⁵⁾ Furthermore, the “bright falx sign” may correlate with a good outcome.¹⁶⁾ This finding highlights the importance of sufficient peripheral penetration of the embolic agent to reach the falx.

Access and Therapeutic Outcomes

When considering the outcomes of MMAE, the impact of access route selection on perioperative outcomes cannot be ignored, in addition to the embolization itself. Recently, the transradial approach (TRA) has been widely adopted not only in cardiology but also in neuroendovascular therapy and is being used as a viable access route for MMAE in CSDH.

Reports focusing on CSDH cases indicate that the procedure may be prolonged in cases with a complex vascular anatomy or when bilateral treatment is required.¹⁷⁾ However, TRA has been reported to be associated with a lower incidence of postoperative delirium because it reduces puncture site complications and allows for early ambulation.¹⁸⁾ These findings suggest the importance of access selection in CSDH cases, in which the older patients constitute the majority. While the choice of the access route should be determined by comprehensively assessing the vascular anatomy, age, comorbidities, and laterality of the lesion, the selection of TRA is based on a certain rationality.

Conclusion

MMAE is emerging as a promising therapeutic option to reduce the recurrence rate of CSDH. Based on the current evidence from randomized trials and the SVIN consensus guideline, adjunctive MMAE may be considered for patients with initial, symptomatic CSDH as an addition to standard treatment; however, evidence remains insufficient to support uniform application across all cases. Standalone MMAE should be limited to carefully selected patients (e.g., asymptomatic or mildly symptomatic cases without an urgent need for surgical decompression, or when surgery is contraindicated) with close follow-up. Future prospective studies should refine risk stratification (e.g., imaging phenotype and antithrombotic status) and evaluate long-term clinical outcomes and cost-effectiveness.

Disclosure Statement

The author declares no conflicts of interest.

References

• 1)  Uno M, Toi H, Hirai S. Chronic subdural hematoma in elderly patients: is this disease benign? Neurol Med Chir (Tokyo) 2017; 57: 402–409.
• 2)  Fiorella D, Arthur AS. Middle meningeal artery embolization for the management of chronic subdural hematoma. J Neurointerv Surg 2019; 11: 912–915.
• 3)  Fiorella D, Monteith SJ, Hanel R, et al. Embolization of the middle meningeal artery for chronic subdural hematoma. N Engl J Med 2025; 392: 855–864.
• 4)  Siddiq F, Shakir M, Nguyen TN, et al. Consensus statement on middle meningeal artery embolization in chronic subdural hematoma treatment: a guideline from the Society of Vascular and Interventional Neurology Guidelines and Practice Standards Committee. Stroke Vasc Interv Neurol 2025; 5: e001814.
• 5)  Estrella López AS, Espin Jiménez NP, Montalvo Ramos PA, et al. Endovascular embolization for chronic subdural hematomas: a literature review of the current evidence. Cureus 2025; 17: e80898.
• 6)  Davies JM, Knopman J, Mokin M, et al. Adjunctive middle meningeal artery embolization for subdural hematoma. N Engl J Med 2024; 391: 1890–1900.
• 7)  Liu J, Ni W, Zuo Q, et al. Middle meningeal artery embolization for nonacute subdural hematoma. N Engl J Med 2024; 391: 1901–1912.
• 8)  Khorasanizadeh M, Maroufi SF, Mukherjee R, et al. Middle meningeal artery embolization in adjunction to surgical evacuation for treatment of subdural hematomas: a nationwide comparison of outcomes with isolated surgical evacuation. Neurosurgery 2023; 93: 1082–1089.
• 9)  Omura Y, Ishiguro T. Middle meningeal artery embolization for chronic subdural hematoma: a systematic review. Front Neurol 2023; 14: 1259647.
• 10)  Tanoue S, Ono K, Toyooka T, et al. Efficacy of tailored treatment strategies for chronic subdural hematoma based on hematoma characteristics and volume: a retrospective observational study. World Neurosurg 2024; 192: e119–e123.
• 11)  Murai S, Ebisudani Y, Haruma J, et al. Nationwide survey of middle meningeal artery embolization for chronic subdural hematoma in Japan. Neurol Med Chir (Tokyo) 2025; 65: 319–325.
• 12)  Salem MM, Kuybu O, Nguyen Hoang A, et al. Middle meningeal artery embolization for chronic subdural hematoma: predictors of clinical and radiographic failure from 636 embolizations. Radiology 2023; 307: e222045.
• 13)  Fuentes AM, Khalid SI, Mehta AI. Predictors of subsequent intervention after middle meningeal artery embolization for treatment of subdural hematoma: a nationwide analysis. Neurosurgery 2023; 92: 144–149.
• 14)  Gupta M, Saha A, Gupta A, et al. Material matters: a systematic review and meta-analysis of the effectiveness of different embolic agents in middle meningeal artery embolization. J Vasc Interv Radiol 2026; 37: 107859.
• 15)  Tanoue S, Ono K, Toyooka T, et al. The short-term outcome of middle meningeal artery embolization for chronic subdural hematoma with mild symptom: case series. World Neurosurg 2023; 171: e120–e125.
• 16)  Nakagawa I, Kotsugi M, Yokoyama S, et al. Extensive roles and technical advances of middle meningeal artery embolization for chronic subdural hematoma. Neurol Med Chir (Tokyo) 2023; 63: 327–333.
• 17)  Salem MM, Sioutas GS, Gajjar A, et al. Femoral versus radial access for middle meningeal artery embolization for chronic subdural hematomas: multicenter propensity score matched study. J Neurointerv Surg 2025; 17: 890–897.
• 18)  Yamamoto M, Fujiwara G, Takezawa H, et al. Transradial versus transfemoral access for middle meningeal artery embolization: choice of the access route considering delirium in the elderly. Surg Neurol Int 2024; 15: 276.