Chronic subdural hematoma (cSDH) is a common neurosurgical disease that is increasing in incidence worldwide. While surgical evacuation can relieve mass effect and alleviate neurologic symptoms, drainage alone does not address underlying cSDH pathophysiology, likely resulting in high rates of recurrence. Middle meningeal artery embolization (MMAE) has emerged as a promising adjunct to conventional cSDH to reduce recurrence risk. Despite positive results from multiple randomized controlled trials demonstrating MMAE efficacy, questions remain about its optimal role in routine patient care. This review summarizes the contemporary management of cSDH, discusses the emerging role of MMAE, and highlights lingering questions and future directions.
Key points
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Chronic subdural hematoma (cSDH) is a common neurosurgical disease that is increasing in incidence worldwide.
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Inflammation and angiogenesis underly the pathophysiology of cSDH and lead to the formation of highly vascularized subdural membranes that continuously exude blood into the SDH space.
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While surgical evacuation can relieve mass effect and alleviate neurologic symptoms, drainage alone does not address underlying cSDH pathophysiology, likely resulting in high rates of recurrence.
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Middle meningeal artery embolization (MMAE) has emerged as a promising adjunct to conventional cSDH to reduce recurrence risk.
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Despite positive results from multiple randomized controlled trials demonstrating MMAE efficacy, questions remain about its optimal role in routine patient care.
Introduction
Chronic subdural hematoma (cSDH) is a common neurosurgical disease that has been growing in incidence in recent years, likely due to global population aging and increased use of anti-thrombotic medications. While cSDH has been recognized as a disease entity for over 3 hundred years, treatment modalities have remained limited, and disease recurrence has remained high despite medical and surgical management. Recently, middle meningeal artery embolization (MMAE) has emerged as a promising adjunct to conventional management that promotes cSDH resorption and prevents recurrence. In this narrative review, we discuss the current state of knowledge for cSDHs, the emerging role of MMAE, lingering questions, and possible targets for future research.
Epidemiology
The incidence of cSDH varies from 8.2 to 14.0 per 100,000 people per year in the general population, and it has generally been increasing over time. Multiple factors may be contributing to the overall rise of cSDH incidence. First, the incidence of cSDH is generally accepted to increase with age; among patients 70 y or older, the incidence of cSDH may be as high as 58 per 100,000 patients per year. Thus, it is likely that the global population aging may be a significant contributor to rising cSDH incidence. Other possible explanations are overall increased use of antithrombotic agents and increased burden of medical comorbidities (eg, liver disease, renal disease, malignancy, etc.) among living adults. These factors can all contribute to not only a high propensity to bleed after minor head injuries but also impaired hemostasis to promote cSDH resorption and resolution. Overall, cSDH incidence is expected to continue increasing, and it is on pace to surpass brain tumors to become the most common cranial neurosurgical disease by 2030.
Pathophysiology
The pathogenesis of cSDH typically begins with a minor head injury, which may often be trivial or even unnoticed. In the past, it was believed that this injury ruptures the bridging veins that traverse the subdural space, leading to the slow accumulation of blood in the setting of age-related brain atrophy and increased negative pressure in the subdural space.
Currently, we believe that in addition to the initial bleeding, dural border cells (DBCs) are also injured, triggering a series of inflammatory and angiogenic responses. The injured DBCs release inflammatory and angiogenic mediators, such as vascular endothelial growth factor (VEGF ) and hypoxia-inducible factor 1 alpha, as well as reparative growth factors (eg, transforming growth factor-beta). Together, these factors lead to the formation of immature vasculature and recruit fibroblasts, leading to the gradual formation of highly vascularized outer and inner cSDH membranes that encapsulate the hematoma.
The newly formed vessels within cSDH membranes are structurally incompetent and are thus prone to ruptures and micro-ruptures. This leads to continued exudation of blood products into cSDHs, resulting in a gradual enlargement of the hematoma. The osmotic and oncotic pressure gradients created by the breakdown of blood cells and the release of proteins also draw more fluid into the subdural space, further increasing cSDH size.
In some cases, endogenous hemostatic pathways can overcome the rate of micro-ruptures and blood exudation, which will lead to net absorption of the hematoma and eventual cSDH resolution over time. However, in many cases, continued inflammation and recurrent bleeding outpaces hemostasis and resorption, leading to net expansion and cSDH persistence.
Imaging and diagnosis
The diagnosis of cSDH is most commonly based on neuroimaging, specifically computed tomography (CT). Classically, cSDH appears crescent-shaped along the cerebral convexity crossing suture lines; however, cSDHs can occur at other locations such as along the falx or base of the skull. The density of subdural fluid collections is an important feature, and it is used to establish the age of SDH; in general, a homogeneously hyperdense lesion suggests an acute hematoma, mixed-density suggests a subacute or acute-on-chronic SDH, while a purely hypodense lesion indicates cSDH or hygroma. Radiographic definitions of cSDH vary; however, iso- or hypo-density comprising 50% or more of the SDH is a widely accepted definition for subacute and chronic SDHs. , Magnetic resonance can also be used to characterize cSDHs, and the appearance of the hematoma on T1 and T2 sequences can be used to determine the age of blood products.
In addition to determining the age of blood products, assessment of cSDH morphology is also important, which can provide key information on prognosticating risk of recurrence. To this end, several classification schemes have been proposed, with the Nakaguchi classification system being the most widely cited. In brief, the Nakaguchi system categorizes cSDH morphology into 4 subtypes: homogenous, laminar, separated, and trabeculated. In general, cSDHs are believed to initiate as homogenous. Subsequently, cSDH membranes form giving rise to the laminar subtype with the appearance of hyperdense membranes. With recurrent bleeding, the cSDH becomes mixed and separated in density, giving way to the separated or gradation subtypes. Finally, continued membrane formation leads to septations of the hematoma into pockets of heterogeneous contents. The recurrence rate associated with each subtype after surgical drainage has varied in the literature; however, the separated subtype has been consistently shown to be associated with a high recurrence rate. Representative images of cSDHs classified by the Nakaguchi system are shown in Fig. 1 .
Conventional treatment modalities
Surgical Evacuation
For significantly symptomatic cSDHs, surgical evacuation is standard treatment, with the goal of quickly alleviating mass effects and improving neurologic symptoms. There are 3 main surgical methods for treating cSDHs: burr hole irrigation and drainage, twist-drill trephination, and large craniotomy. While effective at alleviating neurologic deficits acutely, these procedures carry surgical risks. A systematic review and meta-analysis from 2012 showed that these procedures have complication rates of approximately 25%, 18%, and 25% for burr hole, twist-drill trephination, and large craniotomies, respectively. The recurrence rates for burr-hole drainage and twist-drill trephination are as high as 31% and 33%, likely due to these methods’ inability to remove loculated hematomas or address leaking capillaries in the cSDH membranes. Craniotomies also have a high recurrence rate of up to 28% but craniotomy with membranectomy can reduce this rate to as low as 7.6%. Subdural drains can also reduce recurrence risk. Although large craniotomy with membranectomy can be an effective treatment, it may not be suitable for patients with significant medical comorbidities or those requiring anticoagulation, which might have contributed to the development of the cSDHs. Overall, the current literature suggests that complication rates of surgical evacuation of cSDH can be high, and the risk of hematoma recurrence is substantial.
Medical Management
As many SDHs resolve spontaneously, observant management was considered to be a reasonable approach for smaller hematomas (eg, <1 cm in maximal thickness) without significant mass effect. However, early data have shown that a substantial portion of conservatively managed cSDHs eventually require surgery, and there is currently no accurate predictive model to reliably identify patients who may experience cSDH resolution versus expansion. Several pharmacologic agents have been explored to reduce the recurrence risk of cSDHs. The most studied agent to date is dexamethasone, which has been investigated in multiple randomized controlled trials. In 2020, Hutchinson and colleagues reported in a randomized trial consisting mostly of surgically evacuated cSDH patients that while dexamethasone was associated with a lower rate of cSDH recurrence, it was also associated with higher rates of poor neurologic outcomes. In 2023, Miah and colleagues failed to establish dexamethasone monotherapy as non-inferior to burr-hole treatment in another randomized trial. Thus, the current literature does not support the routine use of dexamethasone for surgical cSDH patients. The effectiveness of dexamethasone for non-surgical cSDH patients is presently unclear.
Other pharmacologic agents have also been explored for the management of cSDH. In 2018, Jiang and colleagues reported in a randomized trial of non-surgical cSDH patients that atorvastatin was significantly associated with cSDH volume reduction compared to placebo. Increased fibrinolysis may also contribute to the pathophysiology of cSDH, and tranexamic acid—a pro-coagulant—has been suggested as a potential treatment. To date, the use of tranexamic acid for cSDH has yielded inconsistent results , ; a randomized trial to further evaluate its efficacy is currently in progress. Finally, bevacizumab—a VEGF inhibitor—has also shown potential promise for preventing cSDH recurrence in a case report and a case series. , Overall, future studies are needed to further investigate the effectiveness of pharmacologic agents for the treatment of cSDH, either as monotherapy or surgical adjunct.
Middle meningeal artery embolization
Rationale
A prevailing hypothesis for the high recurrence rates of cSDHs despite surgical intervention are that simply evacuating the hematoma does not target the subdural membranes or the embedded immature neo-vasculature, which are thought to be responsible for ongoing leakage of blood products into the subdural space. Thus, it is possible that restricting blood supply to cSDH membranes may be effective in inducing membrane necrosis and reducing ongoing blood leakage. The middle meningeal artery (MMA) is the predominant vascular supply for the dura mater and these neo-membranes; thus MMA embolization has emerged as a promising treatment to prevent cSDH recurrence and promote cSDH resorption.
Efficacy
MMAE was initially conceived as a treatment to reduce cSDH recurrence. In 2018, Ban and colleagues showed that MMAE as an adjunct to observant or surgical management was associated with a lower rate of cSDH recurrence. Subsequent studies have corroborated these findings, overall suggesting that MMAE may be effective in reducing rates of cSDH recurrence. By 2023, the overall recurrence rate of cSDH following MMAE was as low as 4% to 7%, which is substantially lower than previous reports for conventionally managed cSDH.
The promising clinical data for MMAE provided the basis for multiple randomized studies to formally study the treatment. In 2024, preliminary results from 3 randomized controlled trials—STEM, EMBOLISE, and MAGIC-MT— were presented at the International Stroke Conference. All 3 trials met their primary efficacy endpoints with good safety outcomes. In STEM, the addition of MMAE to conventional management (either surgery or observation) significantly reduced the incidence of treatment failure at 180 d (15.2% vs 39.2%, P = .0001). In EMBOLISE, the combination of MMAE with surgical intervention notably decreased the rates of 90-day cSDH recurrence compared to surgery alone (4.1% vs 11.3%, P = .008). Finally, in MAGIC-MT, MMAE as an adjunct to conventional management (either surgery or observation) was associated with a decreased rate of death, recurrence, or progression compared to conventional management alone (7.2% vs 12.2%, P = .02). While these results should be interpreted with caution as they are preliminary and pending peer review and formal publication, they support the incorporation of adjunctive MMAE into the standard of cSDH care to prevent disease recurrence.
Safety and Technical Considerations
The most notable risk of MMAE is the unintended embolization of critical vessels (eg, the ophthalmic artery) via vascular anastomoses ( Fig. 2 ). There is also a risk of embolic material reflux into proximal vessels and important branches during MMAE (eg, petrosquamosal branch). However, current clinical data indicate that MMAE is generally safe, with an overall complication rate of about 3% according to the literature, and individual risks of stroke or hemorrhage below 1%, which are similar to the risks involved in extra-cranial embolizations. To reduce the risk of embolization through potentially dangerous anastomoses, it is advised to perform embolization from a microcatheter positioned above the anterior clinoid process on lateral projections, ideally from the frontal (anterior) or parietal (posterior) branches of the MMA. Super-selective and wedged embolization of posterior MMA branches, especially with liquid embolic agents, may also carry more risk of cranial nerve injury as those often provide direct anastomoses to cranial nerves along the petrous ridge. Preliminary results from STEM, EMBOLISE, and MAGIC-MT showed that MMAE did not lead to significantly higher risk of perioperative adverse events, overall supporting the notion that MMAE is a generally safe procedure.
