Article Citation: Fiorella D, Monteith SJ, Hanel R, Atchie B, Boo S, McTaggart RA, Zauner A, Tjoumakaris S, Barbier C, Benitez R, Spelle L, Pierot L, Hirsch JA, Froehler M, Arthur AS; STEM Investigators. Embolization of the Middle Meningeal Artery for Chronic Subdural Hematoma. N Engl J Med. 2025 Feb 27;392(9):855-864. doi: 10.1056/NEJMoa2409845. Epub 2024 Nov 20. PMID: 39565980.

Background

Standard medical and surgical treatment options for chronic subdural hematoma (SDH) are associated with rates of treatment failure approaching 50%. Pathophysiologically, chronic SDH is thought to be the result of meningeal inflammation leading to neovascular proliferation followed by bleeding, creating a positive-feedback cycle that outpaces hematoma resorption. Endovascular middle meningeal artery (MMA) embolization using liquid embolic agents is an adjunctive treatment that aims to abort this feedback loop. The Squid Trial for the Embolization of the Middle Meningeal Artery for Treatment of Chronic Subdural Hematoma (STEM) studied the effect of adjunctive MMA embolization with Squid (Balt USA), a non-adhesive liquid embolic agent, on rates of treatment failure for patients with symptomatic chronic SDH.

Methods:

This study was a prospective, open-label, multi-center, randomized controlled trial which randomized patients with symptomatic chronic SDH larger than 10 mm to standard treatment alone, or standard treatment with adjunctive MMA embolization using Squid. SDH chronicity was determined by radiographic appearance on CT. Standard treatment was chosen for the patient at the discretion of the surgeon prior to randomization and consisted of either surgery (burr hole evacuation or SEPS drainage) or nonsurgical management, leading to four treatment strategies: embolization plus surgical standard treatment, embolization plus nonsurgical standard treatment, surgical standard treatment alone, and nonsurgical standard treatment alone.

The composite primary efficacy endpoint was assessed at 180 days and included residual or recurrent SDH larger than 10 mm; a need for rescue surgery or reoperation; or major disabling stroke, myocardial infarction, or death from neurological causes. The primary composite safety endpoint was major disabling stroke or death from any cause within 30 days of treatment. Secondary endpoints included modified Rankin Scale (mRS) at 180 days as well as peri-procedural adverse events.

Results:

A total of 310 patients were enrolled: 149 patients to standard treatment with adjunctive embolization and 161 to standard treatment alone. Overall, 189 patients underwent surgical treatment (91 in the intervention arm and 98 in the control arm) and 121 patients underwent nonsurgical management (58 in the intervention arm and 63 in the control arm). Mean age was 73, and 70% of patients were men.

In the intention-to-treat population, a primary outcome event occurred in 16% of the embolization group and 36% of the control group (odds ratio [OR] 0.36; 95% CI 0.2-0.66; p = 0.001). In the nonsurgical stratum, a primary outcome event occurred in 19% of the embolization group versus 56% of the control group (OR 0.19, 95% CI 0.08-0.46). In the surgical stratum, a primary outcome event occurred in 14% of the embolization group versus 23% of the control group (OR 0.6, 95% CI 0.27-1.35). Among all primary outcome events, the most common was reoperation.

With regard to the primary safety outcome, death from any cause within 30 days occurred in 3% of both the embolization arm and the control arm, and major disabling stroke within the same timeframe occurred in 0% of the embolization arm and 1% of the control arm. At 180 days, there was no difference in death from neurological cause, major disabling stroke, or mRS, but there was a non-statistically significant trend towards increased mortality in the embolization group.

Commentary:

In this study, patients with symptomatic chronic SDH had a lower incidence of treatment failure when randomized to endovascular MMA embolization using Squid, without an increased incidence of peri-procedural complications. Of note, this effect was stronger among those who underwent nonsurgical management compared to those who underwent surgery. However, adjunctive embolization was not associated with a lower incidence of death or disability at 180 days. The study was limited by factors including unblinded operators as well as missing outcome data in the 15% of patients who did not complete follow up. Nonetheless, the study demonstrates that there may be a significant benefit of adjunctive MMA embolization in a specific subset of patients with chronic SDH.