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Embolization of the Middle Meningeal Artery for Chronic Subdural Hematoma

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Year of Publication: 2025

Authors: David Fiorella, M.D., Ph.D., ..., M.P.H.

Journal: The New England Journal of Medicine

Citation: N Engl J Med 2025;392:855-64.

Link: https://doi.org/10.1056/NEJMoa2409845

Clinical Question

In patients with symptomatic chronic subdural hematoma, does adjunctive middle meningeal artery (MMA) embolization reduce the risk of treatment failure compared to standard treatment alone?

Bottom Line

Among patients with symptomatic chronic subdural hematoma, adjunctive MMA embolization significantly reduced the risk of treatment failure (a composite of hematoma recurrence, reoperation, or major adverse events) compared to standard treatment alone, without increasing the short-term risk of disabling stroke or death.

        Major Points
        STEM was the first randomized trial demonstrating that adjunctive middle meningeal artery (MMA) embolization reduces treatment failure in chronic subdural hematoma — a practice-changing NEJM 2025 publication that established Level 1 evidence for this novel interventional approach.
Primary composite outcome (treatment failure at 180 days) occurred in 16% embolization vs 36% control (OR 0.36, 95% CI 0.20–0.66, p=0.001), with NNT of 5 — one of the largest effect sizes in neurosurgical trials.
Safety was equivalent: major disabling stroke or death at 30 days occurred in 3% of both groups, establishing MMA embolization as safe in this elderly population (mean age ~73).
The benefit was dramatically larger in the nonsurgical stratum (OR 0.19) compared to the surgical stratum (OR 0.60), though the trial was not powered for stratified comparisons — suggesting MMA embolization may be most beneficial as a standalone alternative to surgery.
Used Squid liquid embolic agent (ethylene vinyl alcohol copolymer) for MMA embolization — the first FDA-approved embolic for this indication based on STEM results.
Complements the EMBOLISE trial (also NEJM 2024) which showed similar benefit with Onyx embolization, collectively establishing MMA embolization as a new standard of care for chronic SDH.
Enrolled patients at 32 centers with pre-randomization stratification by surgical vs nonsurgical treatment — a pragmatic design allowing physicians to choose their preferred standard treatment before randomization to ± embolization.
Reoperation rates were dramatically lower with embolization (6% vs 26%), addressing the major clinical challenge of chronic SDH recurrence which occurs in 10-30% of surgically treated patients.
All-cause mortality was numerically higher in the embolization group (8% vs 5%) though not statistically significant and predominantly due to non-neurological causes in this elderly population.
42% of patients were on anticoagulants or antiplatelets — a real-world population where chronic SDH recurrence rates are highest and the benefit of MMA embolization may be greatest.

      

Design

Study Type: Prospective, international, multicenter, open-label, interventional, randomized, controlled trial.

Randomization: 1

Blinding: Open-label for intervention, but some outcome events were adjudicated by a blinded committee.

Enrollment Period: November 2020 through May 2023.

Follow-up Duration: 180 days.

Centers: 32

Countries: Not specified, likely international based on author affiliations.

Sample Size: 310

Analysis: Intention-to-treat.

Inclusion Criteria

Symptomatic chronic subdural hematoma measuring >10 mm in maximum thickness on CT or MRI
Hematoma considered chronic if ≥50% of volume was isodense or hypodense compared to cortical gray matter on CT
Age ≥22 years
Pre-symptom modified Rankin Scale score ≤1 (functionally independent at baseline)
Ability to undergo MMA embolization within 7 days of enrollment

Exclusion Criteria

Pre-symptom modified Rankin Scale score >1 (pre-existing disability)
Previous craniotomy for the current hematoma
Active intracranial infection or meningitis
Bilateral chronic SDH requiring bilateral embolization (protocol amendment later allowed)
Known allergy to embolic agents, iodinated contrast, or dimethyl sulfoxide (DMSO)
Vascular anatomy precluding safe catheterization of the MMA
Life expectancy <6 months due to comorbid conditions
Acute or subacute subdural hematoma (<50% iso/hypodense)

Arms

Field	Control	MMA Embolization + Standard Treatment
Intervention	Either surgical evacuation (burr-hole or SEPS drainage) or nonsurgical management, as determined by the treating surgeon prior to randomization.	Middle meningeal artery embolization with the Squid liquid embolic agent, performed as an adjunct to the pre-selected surgical or nonsurgical standard treatment.
Duration	180 days follow-up	180 days follow-up

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
A composite of treatment failure: recurrent or residual hematoma >10mm at 180 days; reoperation or surgical rescue within 180 days; or major disabling stroke, MI, or neurologic death within 180 days.	Primary	36% (47/129)	16% (19/120)	20.60%	0.001
Modified Rankin Scale score at 180 days	Secondary				0.65 (not significant)
Primary safety outcome (major disabling stroke or death at 30 days)	Adverse	3% (5/166)	3% (4/144)
Death from any cause at 180 days	Adverse	5% (9 patients)	8% (12 patients)

Criticisms

Data were missing for 15% of the intention-to-treat population, potentially due to the older patient population and the COVID-19 pandemic, which could introduce bias.
The decision for reoperation or surgical rescue was at the discretion of the unblinded operator, introducing potential for bias, though most were based on imaging deterioration.
Imaging adjudication by the core laboratory could not be blinded due to the radiopaque nature of the embolic agent.
The trial was not powered to definitively assess the treatment effect within the surgical and nonsurgical strata separately.

Funding

Balt USA

Based on: STEM (The New England Journal of Medicine, 2025)

Authors: David Fiorella, M.D., Ph.D., ..., M.P.H.

Citation: N Engl J Med 2025;392:855-64.

Content summarized and formatted by NeuroTrials.ai.

STEM

(2024)

Objective

To evaluate the effectiveness of SQUID MMA embolization in treating chronic subdural hematoma (SDH).

Study Summary

• SQUID MMA embolization significantly reduced the primary outcome of residual, reaccumulation, re-operation, stroke, MI, or death in patients with symptomatic chronic SDH..

Intervention

Standard care (medical or surgical) +/- MMA embolization.

Inclusion Criteria

310 patients with symptomatic chronic SDH, either measuring ≥ 10 mm or causing mass effect.

Study Design

Arms: Standard Care + MMA Embolization vs. Standard Care Alone

Patients per Arm: Not specified in given information

Outcome

• Primary Outcome Within 180 days (Residual, Reaccumulation, Re-Operation, Stroke, MI or Death): MMA Embolization 15.2%, Standard Care 39.2% (p=0.001). <br>• All Cause Death: MMA Embolization 2.7%, Standard Care 3.1%..

Bottom Line

Major Points

STEM was the first randomized trial demonstrating that adjunctive middle meningeal artery (MMA) embolization reduces treatment failure in chronic subdural hematoma — a practice-changing NEJM 2025 publication that established Level 1 evidence for this novel interventional approach.
Primary composite outcome (treatment failure at 180 days) occurred in 16% embolization vs 36% control (OR 0.36, 95% CI 0.20–0.66, p=0.001), with NNT of 5 — one of the largest effect sizes in neurosurgical trials.
Safety was equivalent: major disabling stroke or death at 30 days occurred in 3% of both groups, establishing MMA embolization as safe in this elderly population (mean age ~73).
The benefit was dramatically larger in the nonsurgical stratum (OR 0.19) compared to the surgical stratum (OR 0.60), though the trial was not powered for stratified comparisons — suggesting MMA embolization may be most beneficial as a standalone alternative to surgery.
Used Squid liquid embolic agent (ethylene vinyl alcohol copolymer) for MMA embolization — the first FDA-approved embolic for this indication based on STEM results.
Complements the EMBOLISE trial (also NEJM 2024) which showed similar benefit with Onyx embolization, collectively establishing MMA embolization as a new standard of care for chronic SDH.
Enrolled patients at 32 centers with pre-randomization stratification by surgical vs nonsurgical treatment — a pragmatic design allowing physicians to choose their preferred standard treatment before randomization to ± embolization.
Reoperation rates were dramatically lower with embolization (6% vs 26%), addressing the major clinical challenge of chronic SDH recurrence which occurs in 10-30% of surgically treated patients.
All-cause mortality was numerically higher in the embolization group (8% vs 5%) though not statistically significant and predominantly due to non-neurological causes in this elderly population.
42% of patients were on anticoagulants or antiplatelets — a real-world population where chronic SDH recurrence rates are highest and the benefit of MMA embolization may be greatest.

Study Design

Study Type: Prospective, international, multicenter, open-label, interventional, randomized, controlled trial.
Randomization: Yes
Blinding: Open-label for intervention, but some outcome events were adjudicated by a blinded committee.
Sample Size: 310
Follow-up: 180 days.
Centers: 32
Countries: Not specified, likely international based on author affiliations.

Primary Outcome

Definition: A composite of treatment failure: recurrent or residual hematoma >10mm at 180 days; reoperation or surgical rescue within 180 days; or major disabling stroke, MI, or neurologic death within 180 days.

Control	Intervention	HR/OR	P-value
36% (47/129)	16% (19/120)	- (0.20 to 0.66 (Odds Ratio))	0.001

Limitations & Criticisms

Data were missing for 15% of the intention-to-treat population, potentially due to the older patient population and the COVID-19 pandemic, which could introduce bias.
The decision for reoperation or surgical rescue was at the discretion of the unblinded operator, introducing potential for bias, though most were based on imaging deterioration.
Imaging adjudication by the core laboratory could not be blinded due to the radiopaque nature of the embolic agent.
The trial was not powered to definitively assess the treatment effect within the surgical and nonsurgical strata separately.

Citation

N Engl J Med 2025;392:855-64.

View Original Publication →

STEM

Embolization of the Middle Meningeal Artery for Chronic Subdural Hematoma

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Criticisms

Funding

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