Beyond recurrence: rethinking the clinical value of middle meningeal artery embolization

Chronic subdural hematomas (cSDHs) are becoming increasingly common in aging populations (1,2). Surgical evacuation remains the standard treatment for symptomatic patients; however, postoperative recurrence remains a major clinical challenge (3). Middle meningeal artery embolization (MMAE) has emerged as an adjunct or alternative strategy to reduce recurrence and treatment failure (4). Recent randomized trials have expanded the evidence base for MMAE, providing consistent evidence of reductions in recurrence-related endpoints in selected settings (5-8). However, recurrence and reoperation, although clinically important, do not fully capture the patient-level effects of treatment. Whether reductions in these endpoints translate into meaningful improvements in neurological recovery and healthcare utilization remains unclear. The post-hoc analysis by Knopman et al. (9) therefore provides a timely opportunity to reassess the role of MMAE beyond recurrence prevention. This commentary reviews the current evidence on MMAE, examines the clinical relevance of outcomes beyond reoperation, discusses endpoint selection for future studies, and considers how MMAE should be implemented in routine practice.

Current evidence for MMAE

In recent randomized trials of subacute and cSDH, EMBOLISE (5) and STEM (7) showed significant reductions in recurrence-related endpoints with MMAE, whereas MAGIC-MT (6) and EMPROTECT (8) did not meet their primary endpoints despite favorable numerical trends in some outcomes. Nevertheless, when considered together with recent systematic reviews and meta-analyses (10-12), the available evidence consistently supports the role of MMAE in preventing recurrence and treatment failure. However, its effects on functional recovery and healthcare utilization remain unclear. Table 1 summarizes the major randomized trials, highlighting outcomes beyond recurrence, including functional recovery and healthcare utilization. In EMBOLISE (5), the prespecified modified Rankin Scale (mRS)-based neurologic deterioration endpoint at 90 days met the non-inferiority margin but did not demonstrate superiority. STEM (7) found no significant difference in mRS at 180 days, and MAGIC-MT (6) reported similar 90-day mRS outcomes between groups. EMPROTECT (8) similarly reported comparable rates of mRS ≥4 at 6 months. A recent meta-analysis that pooled these trials also found no detectable effect of MMAE on functional outcomes, all-cause mortality, or length of stay (11). These findings raise the question of whether recurrence-related endpoints alone can adequately capture the clinical impact of MMAE. If MMAE is to be used broadly, its value should be demonstrated not only by fewer surgical events, but also by measurable benefits in recovery, follow-up burden, or resource use. In this context, the post-hoc analysis by Knopman et al. is particularly relevant because it examined outcomes beyond reoperation in the EMBOLISE surgical cohort.

Beyond reoperation: additional lessons from the EMBOLISE surgical cohort

In their post-hoc analysis of the EMBOLISE surgical cohort, Knopman et al. examined three dimensions of clinical impact beyond the primary endpoint of reoperation. Among the 197 patients randomized to adjunctive Onyx MMAE and 203 to surgery alone, functional outcomes were evaluated according to reoperation status, radiographic hematoma recurrence or progression, and unscheduled physician visits over 180 days. First, the authors showed that patients who required reoperation had worse functional outcomes than those who did not. At both 90 and 180 days, the proportion of patients with mRS scores >2 and worsening mRS scores was significantly higher in the reoperation group, with approximately threefold higher rates of mRS >2 and 2.5-fold higher rates of mRS worsening at 180 days. The adjusted analysis of prospectively collected trial data supports the view that reoperation is not only a technical failure endpoint but also associated with worse functional outcomes. However, residual confounding remains possible. Patients requiring reoperation may differ from those who do not require reoperation in baseline vulnerability, such as frailty, and in hematoma-related factors associated with recurrence. Therefore, this association should not be interpreted as evidence that reoperation directly causes functional deterioration. Second, even among patients who did not require reoperation, adjunctive MMAE was associated with substantially lower radiographic recurrence and progression rates. This observation suggests that MMAE may promote a more durable hematoma resolution beyond the prevention of repeat surgery. This durability may have practical relevance in common postoperative dilemmas, including when to resume antithrombotic therapy after cSDH evacuation. However, whether MMAE can safely support earlier or more reliable antithrombotic resumption remains uncertain (13) and should be directly evaluated in future studies. Third, MMAE was associated with fewer unscheduled physician visits for both SDH-related and all-cause reasons at 90 days and 180 days. A reduction in such encounters suggests that adjunctive MMAE may be associated with a less complicated postoperative course and reduce unplanned postoperative healthcare utilization and associated costs. However, the exploratory nature of this post-hoc analysis should be acknowledged. In addition, recurrence or progression and unscheduled physician visits were reported by the study sites, rather than being centrally adjudicated. These limitations preclude definitive conclusions, and whether fewer unscheduled visits translate into meaningful patient benefit or reduced healthcare costs remains uncertain and should be confirmed in future studies. Nevertheless, the findings raise the possibility that MMAE may have clinically relevant benefits beyond the prevention of reoperation.

Defining clinically meaningful endpoints for future MMAE studies

The analysis by Knopman et al. raised important questions regarding endpoint selection in next-generation MMAE studies. First, future studies should clarify whether MMAE improves neurological recovery and patient-centered outcomes, including quality of life, cognitive function, symptom burden, and return to baseline activity. Recurrence may lead to additional procedures and may be associated with worse recovery trajectories and increased healthcare encounters (14). However, the relationship between recurrence and poor functional outcomes may not be direct. Patients with cSDH are often elderly and frail (15), and functional recovery may be influenced by baseline factors such as preexisting disability, comorbidities, cognitive status, and the severity of the initial neurological presentation. Therefore, recurrence reduction may not necessarily produce a measurable improvement in mRS. For this reason, assessing the clinical value of MMAE requires patient-centered endpoints that capture recovery beyond the radiographic or procedural outcomes. Second, the assessment of the economic value of MMAE may benefit from broader measures of healthcare utilization, including repeat imaging, unscheduled outpatient visits, emergency visits, readmissions, and additional procedures. The value of adjunctive MMAE is likely to be the greatest in patients who would otherwise experience recurrence or progression. However, recurrence cannot be predicted with sufficient accuracy at the individual patient level. As a result, universal adjunctive MMAE may expose many patients to additional procedural costs and treatment burdens. This concern is particularly relevant for patients who would not experience recurrence after standard treatment. Recent cost analyses support this concern and suggest that universal adjunctive MMAE may not be economically justified when the baseline recurrence risk is modest (16,17). Furthermore, this concern is particularly important because the risk of recurrence after standard treatment varies widely. Some observational studies have reported rates as high as 30% (18), whereas more recent pooled estimates suggest an average recurrence rate of approximately 12–13% (3). The control-arm event rates in randomized trials have also differed substantially, indicating that the expected absolute benefit of adjunctive MMAE may vary across patient populations and practice settings. Finally, although the rationale for MMAE is based on the concept that reducing the meningeal arterial supply to the hematoma membranes may promote hematoma stabilization or resolution (19,20), the relationship between this proposed mechanism and downstream clinical outcomes remains incompletely defined. As suggested by Knopman et al., this mechanism may have clinical implications for radiographic hematoma dynamics and postoperative course, including antithrombotic management. Future studies should directly evaluate this mechanism and the associated clinical outcomes.

From EMBOLISE to implementation in routine practice

Beyond the question of which outcomes should be used to define the MMAE value, another important issue is the implementation of MMAE in routine practice. MMAE is not a new concept; however, the level of evidence supporting its use has changed in recent years. Early clinical experience with MMAE for refractory or recurrent cSDH has been reported by Mandai et al. (4). Subsequently, an increasing number of observational studies (21) suggested reduced recurrence or treatment failure in selected patients. More recently, randomized trials have provided high-level evidence supporting the use of adjunctive MMAE for recurrence-related endpoints. Reflecting this shift from observational evidence to randomized data, MMAE is increasingly incorporated into clinical practice in many countries (22-24). For example, in Japan, coverage of MMAE under the public health insurance system was clarified in the 2026 revision of the National Medical Fee Schedule. However, several issues remain unresolved as MMAE enters routine practice. It remains unclear whether MMAE should be routinely added at the time of the initial surgery, reserved for recurrent or high-risk cases, or used as a nonoperative treatment option in selected patients. These issues indicate that a broader implementation requires clearer patient selection, appropriate timing, and procedural standardization. In this regard, additional data from nonsurgical cohorts and ongoing trials, such as the CHESS trial (25), which directly compared MMAE alone with conventional surgical evacuation, are important. At the same time, routine adjunctive MMAE in surgically treated patients should be approached with caution, because many patients recover after standard surgical treatment without recurrence. In low-risk patients, adjunctive MMAE may add procedural risk, physical burden, and healthcare costs without clear direct benefit. Therefore, appropriate patient selection is important. Patients at high risk of recurrence may be potential candidates, and clinical and radiographic risk stratification may help guide this decision. Reported factors include the need for antithrombotic therapy, bilateral hematomas, and specific hematoma imaging patterns (26-28). Further development of reliable recurrence risk stratification scores may support more selective use of adjunctive MMAE. Patients with recurrent cSDH may also represent a clinically relevant subgroup for further evaluation of MMAE, given previous reports of MMAE for refractory or recurrent cSDH (4). Postoperative imaging may help guide patient selection and treatment timing. For example, early postoperative computed tomography (CT) follow-up may identify findings associated with later recurrence after surgical evacuation (29). These findings may help inform subsequent consideration of adjunctive MMAE. Future studies should assess whether treatment selection based on recurrence risk stratification and clinical context can better define the clinical value and appropriate indications for adjunctive MMAE.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Neurointervention. The article has undergone external peer review.

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