Middle meningeal artery embolization and chronic headache: a mini review

Headache disorders are broadly categorized into primary forms, including migraine, tension-type headache, and trigeminal autonomic cephalalgias such as cluster headache, and secondary forms that result from underlying structural or vascular pathology (1).

Chronic migraine, defined as headache occurring on 15 or more days per month for over three months, of which at least eight days meet migraine criteria, remains a highly disabling neurological disorder with substantial personal and socioeconomic impact (2). Despite the availability of multiple preventive medications, including calcitonin gene-related peptide (CGRP) monoclonal antibodies (3), onabotulinumtoxinA (4) and neurostimulation devices (5), a significant subgroup of patients fails to achieve migraine relief. The burden of chronic migraine extends beyond physical pain, often causing emotional distress, social withdrawal, reduced productivity, and poor quality of life levels (6). In such cases, the need for a new and innovative frontier to treat those refractory cases is almost a must.

Middle meningeal artery (MMA) embolization, a well-established treatment for chronic subdural hematomas (cSDH), has been observed to produce marked improvement in headache symptoms among treated patients (7,8). This clinical observation has led to the hypothesis that the dural vasculature itself may serve as a modifiable contributor to cranial pain, and that selective modulation of MMA perfusion could offer therapeutic benefit in primary headache disorders, particularly migraine (9).

Advanced imaging studies, including high-resolution magnetic resonance angiography, have revealed dilation of the MMA during migraine attacks (10,11). This finding is reversible with the use of triptans and CGRP antagonists, both of which are known to reduce headache intensity (12). These observations align with the longstanding hypothesis that the MMA serves as a key pathway for nociceptive signaling in the trigeminovascular system (13,14). The close anatomical relationship of MMA with the dura and its richly innervated perivascular plexus positions it as a conceivable interventional target (15). Histological studies further support this by demonstrating an abundance of nociceptive fibers surrounding the MMA, which may facilitate pain transmission during neurovascular activation (16,17). Therefore, MMA embolization has shown potential as a targeted and more durable treatment option. The rationale stems from growing neurovascular evidence that implicates the MMA as a critical contributor to the pathophysiology of migraine.

Studies on the use of MMA embolization for chronic migraine or other headache treatment continue to emerge. However, we have not yet identified any similar summaries or reviews on this topic. In this mini review, we aim to provide a cutting-edge summary of this field and help elucidate current progress.

Our very first therapeutic approaches utilized intra-arterial (IA) lidocaine alongside methyl-prednisolone infusion into the MMA to achieve temporary analgesia. Patients with status migrainosus or chronic refractory migraine reported immediate and often dramatic relief 24 hours following the infusion (18). Although corticosteroids may provide a transient anti-inflammatory effect, the sustained improvement observed beyond the pharmacologic half-life of both agents suggests a direct modulatory influence on perivascular sensory fibers and trigeminovascular pathways, rather than a short-lived anti-inflammatory mechanism. This clinical observation formed the rationale for exploring permanent occlusion strategies targeting the MMA. Lidocaine’s mechanism of action likely includes transient blockade of sodium channels within perivascular sensory fibers, dampening the afferent input to central trigeminal pathways. In this sense, IA lidocaine serves not only as bridge therapy but also as a diagnostic indicator of potential response to embolization (9). The benefits of IA lidocaine injection within the MMA exceeded the traditional use in primary migraine. More recent studies extended the approach to post sub-arachnoid hemorrhage (SAH) related headache, demonstrating an immediate and complete resolution of headache in majority of treated patients likely due to related vasoconstriction or reversal of vasodilatation of MMA after administration of lidocaine (19).

Permanent occlusion of the MMA using different embolic agents in attempts to help patients with chronic refractory migraines has now been explored in a growing number of clinical trials (NCT06735833, NCT06848166, NCT07044648), supported by emerging clinical studies (20-22). The procedure, performed via a femoral or radial artery approach, involves selective catheterization of the MMA and delivery of embolic material under fluoroscopic guidance. Using various embolic agents including polyvinyl alcohol particles, n-butyl cyanoacrylate, and liquid embolics operators have achieved selective occlusion of the dural branches supplying pain-generating territories (8). Pre-procedural cerebral angiography is essential to identify potentially hazardous anastomoses, particularly with ophthalmic and/or petrosal arteries. When performed meticulously, the procedure has demonstrated high safety and technical success rates (8). This procedure can be completed under minimal “conscious” sedation, and patients can be discharged the same day, making the approach feasible in outpatient settings.

The use of MMA embolization in migraines has shown consistently favorable outcomes across early studies and institutional experiences (8,9). In a recent study, 89% of patients with chronic subdural hemorrhage and concomitant chronic headaches had improvement in their daily headaches and 78% of them had complete resolution of headaches (8). These patients typically represent a highly refractory population, having failed multiple pharmacologic and device-based preventive strategies. Unlike ongoing pharmacotherapy, embolization is a one-time procedure, which offers the added benefit of treatment durability without systemic side effects. The sustained efficacy, particularly beyond 6 months, suggests that embolization may induce long-term modulation of nociceptive processing and central sensitization pathways.

Theoretically, the procedure is thought to work by interrupting the trigeminovascular afferents that originate in the dura and travel along the MMA to reach central pain processing centers. By eliminating blood flow to the distal MMA branches and thereby ablating the perivascular nociceptive nerve endings, embolization reduces the inflammatory signaling cascade and neuropeptide release (such as CGRP and substance P) that amplify migraine pain (16,17,23). Recent studies have suggested that MMA embolization may influence dural perfusion dynamics and trigeminovascular signaling pathways, potentially exerting a neuromodulatory effect (20). These mechanistic insights support the evolving role of MMA embolization as a targeted interventional therapy for refractory chronic headaches (20,21).

Post-procedural imaging in some patients has demonstrated reduced dural enhancement, decreased dural thickening, and loss of abnormal collateral MMA branches, all of which are radiographic indicators that correspond with clinical improvement (8). Moreover, bilateral embolization may be considered in patients with bilateral symptoms or persistent contralateral attacks following unilateral treatment, though this remains an area of ongoing research (20).

Patient selection remains critical, ideal candidates are those with chronic migraines unresponsive to conventional therapies, without contraindications to endovascular intervention. Imaging biomarkers, such as dural enhancement on magnetic resonance imaging or focal hyperemia in the MMA territory, may help identify patients most likely to benefit. Similarly, diagnostic IA lidocaine infusion may serve as a predictor of response, particularly when pain relief correlates with lidocaine distribution territory (20,22). Careful screening angiography remains essential to avoid non-target embolization, especially in patients with anatomical variants. Worthy to mention that there remains a concern that distal MMA branches might refill from collaterals over time resulting in the recurrence of headache symptoms. Such a phenomenon is frequently seen after embolization of dural arteriovenous fistulas. Due to proximal occlusion from initial treatment, retreatment will not be possible. This raises a question whether IA lidocaine injection should be considered rather than completely embolizing the proximal MMA segment.

In the broader context of chronic migraine management, established preventive options include anti-CGRP monoclonal antibodies (3), onabotulinumtoxinA injections (4), and various forms of neuromodulation (5). These therapies primarily modulate neuropeptide release or central pain transmission, often requiring continuous or repeated administration to maintain efficacy. In contrast, MMA embolization represents a peripherally targeted and potentially durable intervention that modifies the dural vascular substrate itself, addressing an upstream component of the trigeminovascular system. Moreover, MMA targeted therapy should be reserved as last resort for patients with migraines refractory to conventional therapies. While head-to-head comparative data are not yet available, this mechanistic difference highlights the complementary and potentially transformative role of MMA embolization for refractory chronic migraine.

Nevertheless, the current body of evidence remains limited, consisting mainly of small observational cohorts and early feasibility studies, with randomized controlled trials now underway to better define safety, durability, and optimal patient selection. Beyond efficacy metrics, these trials may also clarify the duration of benefit, optimal embolic agent selection, and the potential need for bilateral treatment. Meanwhile, advances in embolic materials, including different polymers and particles, may expand the therapeutic profile of the procedure.

The future of MMA embolization for chronic headache management will be shaped by forthcoming clinical trials. Currently, three randomized controlled trials are actively enrolling patients to evaluate headache frequency reduction (Study of the Effectiveness and Safety of Embolization of the Middle Meningeal Artery Using Non-adhesive Materials SQUID 12 and SQUID 18 in the Treatment of Patients with Chronic Resistant Migraine, NCT06848166), (Middle Meningeal Artery Embolization for Refractory Chronic Migraine, NCT06735833) and (Middle Meningeal Artery Embolization for Chronic Migraine, NCT07044648). These studies aim to validate early observational findings and determine long-term safety and efficacy.

In conclusion, although MMA embolization has historically been used for cSDH, its secondary effect of reducing headache symptoms is increasingly recognized as mechanistically significant rather than incidental. Many cSDH patients report significant headache improvement following embolization, likely due to both hematoma stabilization, attenuation of dural irritation and modulation of MMA-derived nociceptive input. While this population differs from migraineurs, the shared mechanism involving MMA-derived afferent input supports the broader applicability of the technique. MMA Embolization represents a promising, mechanism-based therapy for the management of chronic headaches, particularly in refractory types. Its safety profile, procedural efficiency, and potential for sustained benefit place it as a practical alternative to systemic pharmacotherapies. As evidence continues to accumulate and collaborations grow, MMA embolization may soon be integrated into mainstream treatment algorithms for chronic headache syndromes, offering relief to patients with limited therapeutic options.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Adnan Siddiqui and Liqi Shu) for the series “Innovative Frontiers in Neurointervention: Expanding Horizons in Techniques and Applications” published in Journal of Neurointervention. The article has undergone external peer review.

Peer Review File: Available at https://jni.amegroups.com/article/view/10.21037/jni-25-49/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jni.amegroups.com/article/view/10.21037/jni-25-49/coif). The series “Innovative Frontiers in Neurointervention: Expanding Horizons in Techniques and Applications” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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