Embolization of middle meningeal artery for chronic subdural hematoma: Do we have sufficient evidence?

Abstract

Embolization of middle meningeal artery (EMMA) for chronic subdural hematoma (cSDH) is growing in popularity over the last two decade. Several randomized control trials are underway across the world. Indeed, the recent presentation of results from the EMBOLISE (embolization of the middle meningeal artery with onyx liquid embolic system in the treatment of subacute and chronic subdural hematoma), MAGIC-MT (middle meningeal artery treatment) and STEM (squid trial for the embolization of the MMA for the treatment of cSDH) trials at the International Stroke Congress marks a significant development in the field of neurointerventional radiology. The absence of level 1 evidence for EMMA in cSDH underscores the importance of these trials and the need for rigorous evaluation of their results. While the initial findings are promising, further analysis and interpretation are necessary to inform clinical decision-making effectively. We conclude that there may be evidence supporting EMMA for non-surgical cSDH patients, but the evidence for surgical patients is questionable and requires further study. More studies are underway, and hopefully, there will be more evidence on this topic in the coming years.

Embolization of middle meningeal artery (EMMA) for chronic subdural hematoma (cSDH) is growing in popularity over the last two decade.^1–3 Several randomized control trials are underway across the world. Indeed, the recent presentation of results from the EMBOLISE (embolization of the middle meningeal artery with onyx liquid embolic system in the treatment of subacute and chronic subdural hematoma), MAGIC-MT (middle meningeal artery treatment), and STEM (squid trial for the embolization of the MMA for the treatment of cSDH) trials at the International Stroke Congress marks a significant development in the field of neurointerventional radiology.

The absence of level 1 evidence for EMMA in cSDH underscores the importance of these trials and the need for rigorous evaluation of their results. While the initial findings are promising, further analysis and interpretation are necessary to inform clinical decision-making effectively. Lewitt et al. has summarized these trial results. ⁴ The results from the EMBOLISE, MAGIC-MT and STEM trials suggest a potential benefit of using MMA embolization in preventing recurrence or progression of cSDH compared to standard management alone. In EMBOLISE trial, the rate of cSDH recurrence or progression requiring repeat surgical drainage was significantly lower in the EMMA group compared with the control group of surgery alone (4.1% vs 11.3%; relative risk 0.36, 95% confidence interval (95% CI) 0.11 to 0.80, P = 0.0081). In the MAGIC-MT trial, patients who received EMMA (either as an adjunct to cSDH surgery, or in the case of mild disease as a standalone treatment) were significantly less likely (7.2% vs 12.2%; odds ratio [OR] −4.92, 95% CI −9.37 to 0.63, P = 0.02) to require repeat cSDH treatment than the control group (burr hole drainage or conservative treatment). In the STEM trial, management with EMMA was superior to standard management alone in preventing cSDH recurrence or progression (15.2% vs 39.2%; OR 3.60, 95% CI 1.91 to 6.78, P = 0.0001).

By dissecting and evaluating the data from these trials, clinicians can better understand the efficacy, safety and potential limitations of EMMA as a treatment option for cSDH. This comprehensive assessment is essential for guiding treatment decisions and optimizing patient outcomes in routine clinical practice.

To comprehend the evidence supporting the use of EMMA for cSDH, it is essential to examine the findings by subclassifying the results based on whether patients have undergone surgical drainage or not. This approach allows for a more targeted evaluation of the evidence and its implications for clinical practice.

It is important to identify the commonalities among these trials to better understand their implications collectively. All three trials focused on patients with chronic or non-acute SDH, indicating a shared interest in exploring EMMA as a treatment option for this specific patient population. Additionally, they all utilized DMSO-based liquid embolic material for the EMMA procedure (Onyx and Squid). This consistency in approach suggests a unified effort to assess the efficacy and safety of a specific intervention method across multiple studies. Identifying these commonalities helps establish a foundation for comparing and synthesizing the findings from each trial.

Non-surgical drainage patients

For patients who have not undergone surgical drainage, the evidence from the trials suggests a notable difference in outcomes between those treated with EMMA and those who were not. Although the P-values were not separately reported for this subgroup, the effect size appears to be significantly different (Table 1). This subgroup may represent the clearest and most convincing evidence from these trials supporting the use of EMMA in cSDH patients.

Table 1.

Comparison of trial results for non-surgical and surgical drainage patients with chronic subdural hematoma.

Trials	Non-surgical patients		Surgical patients
	Efficacy	P-value	Efficacy	P-value
EMBOLISE	Not reported	Not reported	4.1% vs 11.3%	0.0081
MAGIC MT	1.9% vs 4.7%	Not presented separately	4.7% vs 5.2%	Not presented separately
STEM	19.1% vs 59.2%	0.0001	12.3% vs 25.4%	0.058

Surgical drainage patients

In the subgroup of patients who have undergone surgical drainage, the focus shifts to whether EMMA can effectively reduce the recurrence of cSDH. Among the three trials discussed, only EMBOLISE demonstrated a significant difference in the primary outcome between the EMMA and non-EMMA groups (Table 1). However, it is crucial to consider that this trial reported roughly a 7.2% difference in reaching the primary outcome between the two groups. Additionally, it is noteworthy that this trial experienced a dropout rate of approximately 10% in both the EMMA and non-EMMA subgroups. The combination of this dropout rate and the 7.2% difference in effect size raises questions about the strength of the evidence supporting EMMA in this subgroup. The details of the parameters for the adaptive design of this trial is still unknown and we have to wait for the full publication for this information.

Furthermore, the other two trials, MAGIC-MT and STEM, did not show any significant difference between the EMMA and non-EMMA groups for these surgical patients. This lack of significant difference in outcomes further adds uncertainty to the interpretation of the evidence regarding the efficacy of EMMA in reducing recurrence of cSDH in patients who have undergone surgical drainage.

Patient selection criteria vary among the trials discussed, with the EMBOLISE focusing on patients with mild cSDH (defined as midline shift <5 mm and hematoma thickness <15 mm) and minor symptoms such as headaches. This selection criterion may not fully represent the broader population of cSDH patients typically seen by neurosurgical teams, as many patients with non-localizing symptoms are not routinely operated on. Inclusion of patients with bilateral cSDH in both EMBOLISE and MAGIC MT trials further complicates the interpretation of these results.

One of the primary outcome measures in the STEM trial, which showed the largest effect size, was residual unchanged cSDH measuring 10 mm or more. However, this outcome may not reflect clinical care and is not usually considered a failure of surgery in routine practice. The presentation did not specify the number of patients with this primary outcome compared to other primary outcomes and the final publication may further clarify this.

Blinding of investigators was not consistent across the trials, with all allowing EMMA to take place before surgical drainage. This lack of blinding could introduce bias, as surgeons delivering standard care of surgical drainage would be aware of whether patients had undergone EMMA. Conducting EMMA and surgical drainage under the same general anaesthesia in MAGIC MT further complicates the interpretation of complications from the two procedures.

The two trials: STEM and MAGIC MT, had mixed patient populations of surgical and non-surgical patients, with varying proportions. It is unclear whether the trials factored in these proportions beforehand. Full publication of these trial results will hopefully help answer these methodological questions.

None of the three trials reported the extent of EMMA^5,6 as incomplete EMMA is expected to be less effective than complete EMMA. Although this is relatively new concept, it could shed light on the reasons for recurrences in patients with cSDH who underwent EMMA.

Indeed, we find ourselves at a critical juncture reminiscent of the pivotal moment in 2015 when one trial's results on Endovascular Therapy (EVT) for acute ischemic stroke led to the halting of other trials due to the loss of equipoise. ⁷ However, subsequent to this, five trials were published, all demonstrating a similar effect size.^7–12 This convergence of evidence solidified EVT as the universal standard of care for patients with acute ischemic stroke caused by large vessel occlusion. This historical parallel underscore the importance of continued research and the need for comprehensive evidence to establish new standards of care. However, as opposed to the case of EVT for acute ischemic stroke, where the trial results were consistent across board, the current situation with EMMA for cSDH have very inconsistent results and thus may require a different approach and need continued research.

In conclusion, there may be evidence supporting EMMA for non-surgical cSDH patients, but the evidence for surgical patients is questionable and requires further study. More studies are underway, and hopefully, there will be more evidence on this topic in the coming years. However, it is important not to prematurely stop ongoing trials, as better results from better trials are needed.