INTRODUCTION
Chronic subdural hematoma (cSDH) represents a complex entity that extends beyond a simple blood collection. It typically originates from an initial acute hemorrhage that, rather than resolving, triggers a cascade of processes, including inflammation, fibrinolysis, and angiogenesis [13,18,29,46,72,78]. This leads to the formation of a vascularized neomembrane characterized by fragile and permeable blood vessels [18,37,43]. This neomembrane becomes the primary source of recurrent microhemorrhages, explaining the progressive expansion of the hematoma and the development of associated neurological deficits [23,27,37,43]. In this context, the middle meningeal artery (MMA) plays a key role as the primary blood supply to the neomembrane. For this reason, embolization of the MMA has emerged as a therapeutic strategy. By cutting off blood flow to the neovessels, recurrent hemorrhages are halted and hematoma resorption is promoted, offering the potential to improve patient outcomes.
The incidence of this condition is increasing due to an aging population, especially those taking antiplatelet or anticoagulant medication. By the end of the next decade, it is expected to become the most common cranial neurosurgical disease, with some regions projecting a 53% increase in operative caseload [5,6,72]. The current gold standard remains surgical evacuation, typically through burr-hole drainage or craniotomy, which provides rapid decompression and symptomatic relief [3,34,58,63]. However, recurrence occurs in up to 10-20% of cases, particularly among frail or anticoagulated patients [3,33,57]. Middle meningeal artery embolization (MMAE) has emerged as a minimally invasive alternative that not only reduces recurrence in observational studies but also targets the underlying pathophysiology of inflammation and angiogenesis by occluding the MMA and its vascularized neomembranes [10,53,71,74]. While early evidence and meta-analyses report encouraging safety and efficacy profiles, randomized controlled trials have not yet demonstrated superiority over surgery [15,44,53,66]. For this reason, MMAE should currently be considered an adjunct or alternative in selected scenarios, such as in high-risk surgical candidates or as a prophylactic measure combined with drainage rather than a replacement for conventional evacuation [7,12].
Several ongoing randomized controlled trials (RCTs) are investigating the management of cSDH through embolization. Additionally, ongoing trials are studying other pharmacological agents and perioperative management strategies. This research ensures that we are part of a dynamic field committed to continuous improvement in cSDH management.
OBJECTIVE
The objective of this scoping review is to identify and propose, based on current evidence, potential management pathways for patient selection in chronic subdural hematoma (cSDH) embolization. Given the limited and still emerging number of trials and the absence of a comprehensive synthesis of existing data, conducting a scoping review is essential to systematically map the available literature, highlight knowledge gaps, lay a foundation for future high-quality studies, and guide research directions.
METHODS
We conducted a clinical trial search performed following the PRISMA-ScR protocol (Fig. 1). A search was carried out across several international public clinical trial registries, including the U.S. National Library of Medicine platform clinicaltrials.gov (https://www.clinicaltrials.gov, accessed February 19, 2025), the Australian New Zealand Clinical Trials Registry (ANZCTR, https://www.anzctr.org.au, accessed February 19, 2025), the European Union Clinical Trials Register (https://www.clinicaltrialsregister.eu, accessed February 19, 2025), and the Health Canada clinical trials database (https://www.canada.ca/en/health-canada/services/drugs-health-products/health-canada-clinical-trials-database.html, accessed February 19, 2025). To identify these studies, we included search terms such as “Chronic” to specify disease duration, “Subdural hematoma,” and “Embolization” to determine the therapeutic approach. All existing studies, whether in initiation, ongoing, or completed phases, were included. The PRISMA-ScR flow diagram was also followed in this process. The dual screening was conducted, and when discrepancies arose between reviewers, a third reviewer was involved to resolve them. This approach ensured a more rigorous and transparent selection process. By adhering to PRISMA-SCR guidelines, the methodology followed established best practices.
RESULTS
The initial search yielded 25 active clinical trials on clinicaltrials.gov, sourced from the U.S. National Library of Medicine, and two trials from the Australian New Zealand Clinical Trials Registry. The other previously mentioned sources did not yield any active trials following the search strategy used in this study. None of the included studies had results available at the time of the search. Only 4 (14.8%) are currently completed (EMBOLISE, MAGIC-MT, STEM), and 13 (48.1%) are in the recruitment phase. The remaining studies are either active, withdrawn, or of unknown status (37%).
Most of these clinical trials analyze the efficacy and safety of endovascular management for cSDH. Some studies explore the possibility of embolization with polyvinyl alcohol (PVA) particles as an adjunct to standard treatment (NCT04065113). In contrast, others consider the use of Onyx, SQUID, CYA, TRUFILL, nBCA glue, dimethyl sulfoxide, microcoils, PVA with microcoils, Lipoidol, and PHIL.
Recurrence rates, safety profiles, and effectiveness are repeatedly studied endpoints among researchers, as these outcomes could change the way chronic subdural hematoma is managed (NCT04272996, NCT06772740, NCT04923984, NCT04742920, NCT04410146). Interestingly, embolization is also being explored as a pre-or post-surgical procedure to reduce recurrence rates, not just as a standalone procedure (NCT05220826, NCT04272996). Timing may also be an essential consideration, as seen in the ELIMINATE trial, where perioperative embolization is defined as occurring within 72 hours of surgical treatment. Frail patients are also considered potential candidates who may benefit more from endovascular treatment instead of morbid neurosurgical intervention.
Some trials compare outcomes between embolization after surgery and embolization alone (NCT06163547, NCT04816591), while others compare embolization directly with surgery (NCT05267184).
DISCUSSION
Current landscape and limited published evidence
cSDH remains one of the most common neurosurgical conditions in elderly populations, and surgical evacuation continues to be the cornerstone of its management. Burr-hole drainage and craniotomy provide effective decompression and symptomatic relief, with strong support from randomized controlled trials and meta-analyses [3,16,33,63]. The introduction of surgical drains has further improved outcomes by reducing recurrence rates, consolidating surgery as the standard of care worldwide [3,14,33,63].
Interest in embolization as a therapeutic option is increasing, but clinical trial evidence remains limited (Table 1). Among ongoing studies, only a few randomized controlled trials, such as EMBOLISE, MAGIC-MT, and STEM, have reported preliminary findings, none of which include long-term outcomes. With this, we can develop potential management strategies to question the next steps toward the future directions we suggest (Fig. 2). This highlights both the promise of the technique and the immaturity of the current evidence base.
At present, embolization should be regarded as an emerging therapy under investigation rather than a replacement for conventional surgery. While it shows potential in reducing recurrence, high-quality prospective validation is still required.
Over 60% of ongoing trials remain in active recruitment, suggesting that the coming years will be decisive in shaping whether embolization becomes a new standard or complementary strategy. Most studies focus on three outcomes: recurrence, safety, and clinical efficacy parameters that may ultimately drive a shift in management paradigms. Trials such as ELIMINATE also address the timing of embolization relative to surgery, raising essential questions about the optimal therapeutic window.
Despite surgical efficacy, recurrence rates after burr-hole drainage reach 10-20%, particularly in frail or anticoagulated patients [3,33,52,56]. These limitations have motivated the exploration of alternative or adjunctive strategies, with MMAE emerging as a leading candidate.
MMAE directly targets the vascular supply of the fragile neomembrane, which is responsible for recurrent bleeding, aiming to promote hematoma resolution and lower recurrence rates [7,10,12,15,71]. Observational studies and meta-analyses report high rates of hematoma resolution (≥85%) and recurrence below 10%, with relatively few complications [7,12,14,15,73]. However, most data come from retrospective cohorts and small case series, with considerable heterogeneity in patient selection, embolic agents, and outcome definitions [7,8,26,71].
Although clinical interest in MMAE is rapidly growing, published trial data remain preliminary. Of the 27 active studies identified in our search, only four (14.8%) are completed, while thirteen (48.1%) are still recruiting; the rest are ongoing, withdrawn, or of uncertain status. Preliminary results from EMBOLISE, MAGIC-MT, and STEM are encouraging, but long-term outcomes (≥12 months) are not yet available. These facts underscore both the field’s momentum and the urgent need for confirmatory evidence before practice patterns can change.
In parallel, translational and pharmacological research is investigating adjuvant strategies such as corticosteroids, tranexamic acid, and statins to modulate inflammation, fibrinolysis, and angiogenesis [18,25,41,48,68,81]. These efforts reinforce the notion that cSDH management is shifting toward a multimodal and individualized approach rather than a single therapeutic pathway.
Overall, the current landscape is defined by a strong surgical foundation, promising yet preliminary endovascular data, and an active exploration of pharmacological adjuvants. Future research must clarify technical variables, safety considerations, and optimal integration of embolization into treatment algorithms.
Variability in embolic agents and techniques
The considerable variability in embolic agents used across clinical trials underscores the lack of consensus on the optimal material for MMA embolization. This variability may hinder reproducibility, limit standardization, and represent a methodological challenge for future direct comparisons between studies. Each embolic agent possesses unique physical and biological properties that influence procedural technique, angiographic endpoints, and long-term clinical outcomes [26,49,54,74,75,76]. Thus, the choice of embolic material is a critical component that reflects both the complexity and the ongoing evolution of this therapeutic approach.
Polyvinyl alcohol (PVA)
Polyvinyl alcohol (PVA) particles are synthetic, permanent, and non-biodegradable embolic materials widely employed in interventional radiology for vascular occlusion [77]. Their mechanism of action involves adherence to the endothelial wall, triggering a localized inflammatory response that promotes clot formation and results in permanent vessel occlusion [49].
In the setting of cSDH, PVA particles have been explicitly used to occlude the MMA. Several ongoing clinical trials are assessing their role as an adjunct to standard surgical treatment, notably trial NCT04065113. Reported particle sizes range between 50 and 150 μm. The advantages of PVA include a long-standing history of clinical application, well-documented safety, and efficacy in cSDH embolization [74]. Additionally, its irregular morphology facilitates efficient vessel occlusion with smaller material volumes compared to more uniformly shaped microspheres [49].
Despite these benefits, PVA has essential drawbacks. Distal migration of particles may lead to non-target embolization, raising the risk of unintended ischemic complications. Furthermore, aggregation of PVA particles can obstruct the microcatheter or cause embolization more proximally than intended. Another significant concern is vessel recanalization over time, particularly problematic in cSDH, where ongoing angiogenesis in the neomembrane contributes to hematoma persistence and recurrence [74]. These limitations underscore the ongoing search for embolic agents that can ensure more durable and predictable occlusion.
Onyx
In the context of cSDH, Onyx is one of the most studied agents in endovascular approaches. Several clinical trials, such as EMBOLISE (NCT04402632) and OTEMACS (NCT04742920), are evaluating the safety, efficacy, and impact on recurrence of symptomatic cSDH following treatment with Onyx.
One of the main advantages of Onyx is its non-adhesive nature, which significantly reduces the risk of catheter adherence compared with agents such as nBCA. This property enables more controlled, prolonged injections, ideal for precise embolization [26]. Another key advantage is the availability of different viscosities (Onyx 18 and Onyx 34) and the option to dilute the compound, allowing the operator to adapt the agent to the vascular anatomy and flow characteristics. Dilution of Onyx has been associated with greater volume delivery and accelerated hematoma resolution, likely due to improved penetration into the fragile neomembrane microvasculature [30].
This flexibility in tailoring the agent provides significant clinical benefits, enabling more effective embolization and faster patient recovery. However, Onyx is not without disadvantages: it can create substantial artifacts on follow-up computed tomography (CT) scans, potentially hindering hematoma assessment, and prolonged injections may cause transient loss of fluoroscopic visibility. Furthermore, Onyx requires pre-injection preparation (e.g., vial agitation to homogenize tantalum), which can prolong procedure time [26,74,76].
SQUID
SQUID is a non-adhesive liquid embolic agent with a composition very similar to that of Onyx. It is formulated with an ethylene-vinyl alcohol copolymer (EVOH) dissolved in dimethyl sulfoxide (DMSO) and contains micronized tantalum powder for radiopacity [55]. A distinctive feature of SQUID is the advanced micronization of tantalum, which allows slower precipitation and a more homogeneous suspension [55,64,75,76].
In the context of cSDH, SQUID has gained clinical relevance and is currently being evaluated in international multicenter clinical trials, such as the STEM study (NCT04410146), which focuses on the safety and efficacy of MMA embolization using this agent. SQUID has been studied both as a standalone procedure and as an adjunct to surgery. A prospective clinical study demonstrated a significant reduction in hematoma thickness, with a median of 0 mm at 6 months, highlighting its efficacy in resolving cSDH [64].
Among its advantages is improved fluoroscopic visibility during prolonged injections compared with Onyx, attributed to the micronization of tantalum, which provides more precise injection control and better lesion occlusion [49]. Additionally, lower-viscosity formulations (e.g., SQUID 12) enhance distal penetration into the neomembrane microvasculature [47,48]. However, as with Onyx, SQUID may generate substantial artifacts on CT imaging, complicating follow-up assessment [55,64,75,76]. Preparation times can also be longer compared to other embolic agents. Despite these limitations, its improved visibility and stable radiopacity translate into enhanced procedural safety and efficacy, enabling more accurate control of embolic delivery in the fragile vasculature of cSDH [55,75].
Cyanoacrylate (CYA) / n-Butyl cyanoacrylate (nBCA) glue
N-butyl cyanoacrylate (nBCA), commonly referred to as medical “glue,” is a low-viscosity liquid embolic agent used to achieve rapid and permanent vascular occlusion. Its mechanism of action is based on instantaneous polymerization and hardening upon contact with body fluids, forming a solid cast that occludes the target vessel [35,76]. Typically, nBCA is mixed with ethiodized oil (Lipiodol) to impart radiopacity and regulate polymerization speed; tantalum powder may also be added to enhance visualization. The rate of polymerization is directly proportional to the concentration of nBCA—higher concentrations polymerize faster. However, this process releases heat, which can injure the vascular wall and, in some cases, induce acute necrotizing vasculitis. To prevent premature polymerization inside the catheter, flushing with 5% dextrose solution (D5W) before injection is required [40].
In cSDH, the use of nBCA is being evaluated in trials such as LEADH (NCT05374681), which hypothesizes that cyanoacrylate could reduce recurrence due to its ease of use and lower cost. A North American multicenter study has demonstrated technical feasibility and favorable safety, particularly when using the “D5W push” technique [1]. Advantages of nBCA include its ability to induce rapid and permanent thrombosis [1,40]. Furthermore, dilution with Lipiodol enables customization of penetration and radiopacity. Reports also describe shorter fluoroscopy times and lower costs compared to Onyx [1,40,54]. Disadvantages include risks of catheter adhesion, premature polymerization, and thermal injury to the vascular wall [40]. Mastery of injection technique and experience are critical to optimize outcomes and minimize complications.
PHIL
PHIL represents a significant innovation in the endovascular management of cSDH. It is composed of copolymers of polylactide-co-glycolide and polyhydroxyethylmethacrylate dissolved in DMSO, with covalently bound iodine (triiodophenol) providing intrinsic radiopacity. This eliminates the need for tantalum and the requirement for prior agitation before administration. PHIL is available in different concentrations and viscosities, including LV (low viscosity), 25%, 30%, and 35%. Upon injection, PHIL solidifies after DMSO dissipation, exhibiting a “column-like” behavior and producing fewer artifacts on imaging [76]. Its efficacy in cSDH is currently under evaluation in clinical trials [74,76].
The main limitation of PHIL is the lack of long-term comparative data on safety and efficacy compared with more established agents. Nevertheless, its improved radiopacity and reduced imaging artifacts are essential advantages for accurate post-procedural monitoring, potentially optimizing both clinical management and future comparative research [74,76].
Pharmacological adjuvants
Corticosteroids
Corticosteroids, such as dexamethasone, are potent anti-inflammatory agents believed to act in cSDH by reducing inflammation and vascular permeability, thereby preventing fluid accumulation [3,17,18]. Although the precise mechanism remains incompletely understood, their anti-inflammatory effect is thought to explain the reduction in recurrence observed in clinical series (Table 2). Meta-analyses suggest that adjuvant corticosteroids, when combined with surgery, may significantly reduce the risk of recurrence, though without demonstrated positive impact on overall mortality or long-term functional outcomes [17,28,68].
The Dex-CSDH trial (NCT03332014), a pivotal phase III randomized controlled study conducted in the UK, is currently assessing whether a two-week course of dexamethasone can improve six-month functional outcomes by reducing reoperations and hospital readmissions [41]. This trial is expected to clarify whether corticosteroids should be incorporated into standard practice.
Steroids have also been explored as a conservative treatment in selected patients with mild or asymptomatic cSDH, aiming to avoid surgery in high-risk populations [28,68]. However, their use outside clinical trials remains controversial due to potential adverse effects, including immunosuppression, hyperglycemia, and increased infection risk. Current evidence therefore supports their role only as an adjunct to surgery or in carefully selected nonsurgical cases [8,28,41,68].
Tranexamic acid
Tranexamic acid (TXA) is a synthetic lysine analogue and potent antifibrinolytic agent that inhibits the conversion of plasminogen to plasmin, thereby stabilizing fibrin clots and reducing the risk of continued microhemorrhage [51]. In the context of cSDH, this mechanism has been hypothesized to counteract the fragile vascularity of the neomembrane, which is prone to recurrent bleeding episodes and hematoma expansion. As such, TXA has been proposed both as an adjunct to surgical evacuation and as a possible non-surgical option in select patients [32,48].
Evidence to date remains limited. A meta-analysis pooling four randomized clinical trials (RCTs) reported that TXA use did not significantly reduce postoperative hematoma volume or recurrence rates. However, a trend toward earlier and more complete resolution of cSDH following burr-hole drainage was observed in the TXA groups compared to controls [48]. This suggests a potential biological effect, though the current body of evidence is underpowered to establish efficacy.
Regarding safety, TXA appears reassuring in the setting of cSDH. Across available RCTs, no significant adverse events such as thromboembolic complications were reported, supporting a favorable safety profile in elderly and comorbid populations [32,48,51]. Importantly, these findings contrast with concerns historically associated with antifibrinolytics in other clinical contexts and reinforce the possibility that TXA may be safe when carefully applied in cSDH management.
Nevertheless, several limitations must be acknowledged. First, the lack of statistically significant reductions in recurrence prevents any recommendation for routine use at this stage. Second, existing studies are heterogeneous in terms of dosing regimens, treatment duration, and timing relative to surgery, complicating direct comparison and interpretation. Third, none of the available trials adequately stratified patients by risk groups (e.g., anticoagulated vs. non-anticoagulated, unilateral vs. bilateral hematomas), leaving uncertainty about which subgroups may benefit most. Finally, the longest follow-up periods rarely extended beyond six months, leaving unanswered questions about long-term efficacy and durability of TXA’s effect.
While TXA has shown signals of benefit in cSDH resolution with an acceptable safety profile, the current evidence is insufficient to alter clinical practice. TXA should be considered investigational pending results from larger, multicenter RCTs designed to clarify its role as either an adjuvant or a conservative therapy. Future research should prioritize standardized protocols, stratification by risk profile, and longer follow-up to determine whether TXA can be incorporated into evidence-based algorithms for cSDH management.
Statins
Statins, HMG-CoA reductase inhibitors, exert pleiotropic effects beyond lipid lowering. In the context of cSDH, they modulate inflammation, angiogenesis, and coagulation, processes that are central to hematoma persistence and recurrence [25]. Experimental and clinical evidence indicate that statins promote the maturation of neomembrane vasculature, thereby enhancing vessel stability and reducing the propensity for microhemorrhages [34,81]. In parallel, their anti-inflammatory properties contribute to limiting exudation and edema, interrupting one of the self-perpetuating mechanisms of hematoma expansión [25,34,81].
This multifaceted action positions statins as a promising pharmacological option that may be integrated into different stages of cSDH management. They have been investigated as a conservative treatment in patients unfit for surgery, as an adjuvant to reduce recurrence after evacuation, and, potentially, in combination with embolization to modulate the inflammatory and angiogenic cascades [25,34,81].
Clinical evidence, although still limited, has provided encouraging results. Two randomized trials demonstrated that atorvastatin was safe and effective in reducing hematoma volume and improving neurological function in adults with cSDH [34,45]. In conservatively managed patients, statin therapy was associated with significant reductions in hematoma size, improved functional outcomes, and a decreased need for surgical intervention [34,45,81]. Furthermore, preoperative use of statins has been linked to greater postoperative reduction in cSDH volume, suggesting a potential role in perioperative optimization [25].
Despite these promising findings, essential caveats remain. Most studies have been single-center and relatively small, limiting generalizability. Follow-up durations have often been short, and optimal dosing regimens remain undefined. Moreover, while their favorable safety and cost profile make them particularly attractive for elderly patients with comorbidities, robust multicenter randomized trials are still required to confirm their role.
Management of antiplatelet and anticoagulant therapy in cSDH patients
The management of patients with cSDH who require long-term antiplatelet or anticoagulant therapy remains one of the most challenging aspects of clinical practice. These medications significantly increase the incidence of cSDH, particularly in elderly populations with vascular comorbidities, and at the same time complicate perioperative decision-making for major neurosurgical interventions such as craniotomy [4,24,47,57]. The central dilemma lies in balancing the elevated risk of hemorrhage associated with continuing these agents against the equally serious risk of thromboembolic events when they are discontinued. For example, in patients with atrial fibrillation or prosthetic heart valves, interrupting antithrombotic therapy can expose them to life-threatening systemic embolism or ischemic stroke [11,47,57]. Thus, management requires an individualized, carefully calibrated approach that accounts for both bleeding and ischemic risks.
Encouragingly, recent clinical evidence suggests that the perioperative management of these drugs may be more flexible than previously assumed. Pre-intervention antiplatelet use did not prolong hospitalization or increase complication rates, and resuming therapy after cSDH evacuation was not associated with higher rates of new hemorrhage or surgical reintervention [61]. Furthermore, studies indicate that early resumption of antithrombotic therapy, typically within one to four weeks after surgical evacuation, can reduce the risk of thromboembolic complications without increasing the likelihood of recurrent bleeding [22,42,61]. Importantly, neither antiplatelets nor anticoagulants have been shown to influence recurrence rates of cSDH or long-term functional outcomes significantly [22,61]. These findings support a more proactive approach to reinitiating therapy, especially in patients with high thromboembolic risk.
Within this therapeutic paradox, MMA embolization has emerged as a desirable option. By targeting the neomembrane vasculature responsible for recurrent bleeding, MMAE offers the potential to control hematoma progression while allowing patients to continue their essential antithrombotic medications [2]. Several reports suggest that embolization can serve as an effective adjunct to surgical evacuation in anticoagulated patients, and in some cases, as a standalone therapy when interruption of antithrombotic therapy is deemed unsafe [36,70]. This strategy is especially relevant for frail elderly patients or those with strong cardiovascular indications for uninterrupted anticoagulation.
Nevertheless, important limitations must be acknowledged. Most available studies are observational, and protocols for resuming antithrombotics vary considerably across institutions. Randomized evidence remains lacking; therefore, current practice should remain individualized, based on thromboembolic risk stratification and careful neurosurgical-cardiology collaboration.
Anatomical characteristics and technical considerations of MMA embolization
The embolization of the MMA requires strategic decision-making informed by a precise understanding of its anatomy. The MMA typically bifurcates into anterior and posterior branches, each defined by distinct vascular territories and anastomotic patterns that critically influence procedural planning [69,80]. The anterior branch supplies the frontal and parietal dura and forms anastomoses with the ethmoidal arteries, branches of the ophthalmic artery. These connections necessitate meticulous caution to prevent non-target embolization and subsequent visual complications. The posterior branch supplies the posterior dural regions and may anastomose with the occipital or posterior meningeal arteries [39,67,69,80].
From a technical standpoint, transradial access is increasingly preferred over femoral access due to its enhanced safety and efficacy, particularly in elderly patients with heightened vascular risk [59]. The procedural objective is to achieve a “wedged” microcatheter position, facilitating deep penetration of embolic material toward the vertex and collateral network while mitigating the risk of ophthalmic involvement [50,65,67,79]. Injections must be performed gently to avoid unintentional embolization into the superior sagittal sinus [60,65]. Retrograde embolization from distal to proximal segments is recommended, as it induces progressive occlusion of the neomembrane vasculature sustaining the hematoma and minimizes reflux through hazardous anastomoses. This technique enhances both safety and devascularization efficiency, especially in meningo-ophthalmic and meningo-lacrimal variants that are prone to off-target embolization. Conversely, proximal embolization at the level of the foramen spinosum entails greater risk owing to potential anatomical variations involving the MMA and the ophthalmic artery [50,65,79]. Generally allow for proximal occlusion of the MMA, being careful to stop short of the petrosal branch of the MMA to reduce the risk of injury to the facial nerve [20,50].
There remains considerable variability among operators regarding procedural extent and vascular targeting, limiting interstudy comparisons and hindering consensus. Some interventionalists advocate selective embolization of the branch supplying the hematoma, typically the anterior branch, while others favor comprehensive occlusion of both branches to reduce theoretical recurrence from collateral perfusion [9,31]. Distal embolization near the dura mater is widely regarded as the optimal approach for achieving a focused therapeutic effect; however, proximal occlusion of the main trunk remains technically simpler [9,10,50,65,79].
Currently, no prospective studies have demonstrated definitive differences in clinical outcomes between selective and bilateral branch embolization. Preliminary data suggest that a more extensive approach may enhance the penetration of embolic agents and reduce recurrence. Still, vessel selection and embolization level (proximal versus distal) should be individualized based on patient anatomy, procedural risk, and operator experience. To date, differences in outcomes attributable to segmental selection have not reached statistical significance. Present technical choices therefore rely on patient-specific vascular architecture and risk stratification. Future evidence is necessary to define the optimal embolization paradigm and to clarify the impact of segmental approaches on long-term clinical outcomes.
Complications related to MMA embolization procedure
Complication rates are consistently reported as low, ranging from 2% to 5% [1,62,66]. These numbers must be interpreted with caution. The apparent safety profile is encouraging, but should not minimize the gravity of individual events, some of which can be devastating. Moreover, reporting biases, variable definitions of “complication,” and heterogeneous follow-up durations across studies may underestimate risks, underscoring the need for rigorous and standardized adverse event reporting.
General safety profile
A systematic review of 43 studies (n=2,783) documented an overall complication rate of 2.3%, with severe complications in 1.0% of patients and two procedure-related deaths [53]. Another meta-analysis of 34 studies (n=921) reported a system-specific breakdown: neurological 3.8%, cardiovascular/vascular 3.6%, infectious 2.9%, and miscellaneous 3.1% [64]. A specific assessment of octogenarians and nonagenarians reported 5.8% complications and 1.2% in-hospital mortality, suggesting that MMAE remains safe even in high-risk elderly cohorts. However, complication rates are modestly higher than in younger populations [38].
Taken together, these data confirm that MMAE is relatively safe compared with traditional surgical evacuation. However, rare but severe complications such as stroke, blindness, or procedure-related death highlight the need for vigilance.
Neurological complications
Neurological events constitute the majority of complications, occurring in ≈3.8% of cases [66]. They include seizures, transient aphasia or hemiparesis, ischemic stroke, and asymptomatic infarcts. Among the most feared is vision loss, caused by reflux of embolic material into the ophthalmic circulation through meningo-ophthalmic anastomoses. Central retinal artery occlusion has been reported most frequently with particulate agents (e.g., PVA) or non-adhesive liquid embolics (Onyx, SQUID) [8,66,76]. Severe events included cerebral infarction and permanent visual loss, both carrying profound morbidity [53,66].
The angiographic prevalence of ophthalmic-origin MMA is not negligible, estimated at 13-14% in dedicated anatomical series [19]. This underscores the critical importance of pre-procedural angiography to identify hazardous anastomoses. Failure to recognize these connections can transform a “low-risk” procedure into a catastrophic event.
Cardiovascular and vascular complications
Vascular events occur in ≈3.6% of cases. These include MMA rupture, arterial dissection, arteriovenous fistula formation, and access-site complications such as femoral pseudoaneurysm or occlusion [66]. While often manageable, these events may prolong hospitalization and expose patients to further interventions. Risk appears higher in patients with severe atherosclerosis or tortuous access vessels, explaining the growing preference for transradial access, which has shown lower complication rates than transfemoral approaches, particularly in frail elderly patients [37,59].
Infectious and miscellaneous complications
Infectious complications (≈2.9%) typically manifest as peri-procedural pneumonia or empyema, particularly in immobilized elderly patients [66]. Though not directly related to the embolization itself, they contribute significantly to morbidity. Miscellaneous and technical complications (~3.1%) include guide-catheter herniation, retained microcatheter, and, in rare cases, procedure-related death.66) While infrequent, these highlight the need for meticulous technique and team preparedness.
Patient selection and risk modifiers
Complication rates are influenced by comorbidity burden and age. In one meta-analysis, studies excluding patients with significant comorbidities reported significantly lower complication rates, suggesting that careful selection improves safety [66]. Another analysis highlighted that elderly patients (≥80 years) remain acceptable candidates, though they face slightly higher risks [38]. These findings stress that safety is not uniform across all populations, and stratified approaches are essential.
Integrating safety into clinical practice
Despite a low global incidence of adverse events, MMAE complications can have permanent, life-altering consequences. For this reason, embolization should not be portrayed as “risk-free” or “superior to surgery”. Instead, its risk profile is best described as acceptable but agent-dependent, anatomy-dependent, and operator-dependent. Operator experience, institutional protocols, and patient characteristics all shape outcomes.
Moving forward, prospective RCTs must include standardized reporting of complications, detailed angiographic endpoints, and subgroup analyses by age and comorbidity to refine safety profiles. Only then can accurate risk-benefit ratios be established.
Future directions: Suggested clinical decision-making algorithm
Given that this is a topic of growing interest, supported by various research studies, we proposed an approach for the general management of cSDH, including cases in which embolization could be beneficial, either as a standalone procedure or in combination with craniotomy or burr hole drainage.
According to our proposal, the management of cSDH is primarily based on the patient’s neurological status. On the one hand, if cSDH is found incidentally on radiological imaging, endovascular intervention via embolization may be considered, or warning signs and bimonthly CT scanning may be considered; however, this still needs to be clearly defined, as no study has established the definitive management of asymptomatic cSDH (Fig. 2).
In patients with a neurological deficit, according to MAGIC-MT, surgical drainage is recommended [44]. On the other hand, MMA embolization should not be ruled out in asymptomatic patients, as EMBOLISE suggests this is a promising treatment. Based on the clinical outcome, one of the following treatment routes can be chosen: If symptoms resolve, consider the case resolved and continue with bimonthly CT follow-up. If symptoms accompany recurrence, surgical drainage is suggested. If the initial intervention involves a craniotomy or burr hole drainage, prophylactic MMA embolization is recommended. If asymptomatic recurrence is detected radiologically, MMA embolization is a viable option if it has not been performed yet. Although we suggest MMA embolization, there is limited evidence supporting the superiority over surgical drainage. This algorithm serves as an overview for future directions, not as the standard of care.
Comorbidities must always be considered to individualize the case and select the most appropriate procedure, whether open or minimally invasive. In cases where a patient with cSDH is receiving antiplatelet or anticoagulant therapy that cannot be suspended, the best alternative, according to STEM, may be MMA embolization, continuing along the same treatment pathway for follow-up [21].
On the other hand, if we are dealing with cases of acute exacerbation of cSDH, surgical drainage is recommended, where prophylactic MMA embolization pre- or post-drainage can be considered. In some cases, adjuvant pharmacological therapy may be considered. Afterward, follow-up will depend on the clinical presentation and whether symptomatic recurrence occurs.
Knowledge gaps are undoubtedly present, as there is no standardized timing for embolization. Pre- or post-MMA embolization is also an undefined subject. However, some research has been conducted in this area; there is no clear consensus on the procedural timing standardization of MMA embolization and follow-up CT scan. Another challenge would be to define the effectiveness of MMA embolization compared to surgical drainage alone.
Limitations
The current evidence on middle meningeal artery embolization (MMAE) for chronic subdural hematoma (cSDH) has several key limitations. Although 27 clinical trials are registered worldwide, the vast majority remain ongoing, with only a minority having published preliminary results. This severely limits the ability to draw definitive conclusions and requires caution when translating early findings into practice.
Substantial heterogeneity exists across trials regarding patient selection (e.g., symptomatic versus asymptomatic cSDH, unilateral versus bilateral disease), choice of embolic agents (PVA, Onyx, SQUID, nBCA, PHIL), timing of intervention (primary versus adjunctive, preversus postoperative), and technical strategies (branch selection, embolic volume, angiographic endpoints). This variability complicates direct comparison of outcomes, limits reproducibility, and undermines the strength of pooled analyses.
Furthermore, methodological limitations, such as incomplete protocol transparency and inconsistent reporting of baseline characteristics—such as comorbidities, antithrombotic use, or neurological status—further restrict the generalizability of current findings.
Finally, the scarcity of completed randomized controlled trials with long-term follow-up represents the most critical gap. While several landmark studies are underway, their preliminary results do not yet provide definitive evidence regarding long-term efficacy, recurrence prevention, or superiority over surgical evacuation. These gaps underscore the critical need for standardized, collaborative research, which this scoping review aims to inform.
CONCLUSIONS
Endovascular management of chronic subdural hematoma, particularly through MMAE, represents a promising but still developing therapeutic option. The growing number of registered clinical trials reflects expanding global interest in this approach. However, the lack of definitive randomized evidence and standardized procedural protocols currently limits its integration into clinical practice.
Surgical evacuation via burr-hole drainage or craniotomy remains the established standard of care. MMAE should be considered an adjunctive or investigational therapy, with potential roles in recurrence prevention, in patients requiring continuous antithrombotic therapy, and in carefully selected cases, but not as a first-line treatment.
Future studies must clarify the optimal timing of embolization, compare the effectiveness of different embolic agents, establish standardized angiographic and clinical endpoints, and provide long-term safety and efficacy data. Successfully addressing these gaps will finally enable MMAE to transition from a promising, investigational technique to an integral component of evidence-based guidelines for cSDH management.
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