The Efficacy of Xeomin as a Prophylactic Therapy for Migraine in Patients With Traumatic Brain Injuries (TBIs) Versus Anomalous Health Incidents (AHIs)

Headaches with migraine-like characteristics are a common sequelae of traumatic brain injury (TBI)¹-⁴ and Havana syndrome, otherwise known as anomalous health incidents (AHIs).⁵,⁶ In TBI patients, direct biomechanical forces lead to cellular injury and neuroinflammation, contributing to post-traumatic headaches. Specifically, the disruption of trigeminovascular pathways and the release of inflammatory mediators, such as calcitonin gene-related peptide (CGRP), are implicated in the pathophysiology of post-traumatic migraines. Furthermore, the presence of comorbid conditions, such as post-concussive syndrome, can exacerbate headache symptoms and complicate treatment strategies.⁷ Though the migraine-like headaches in patients with AHI are clinically similar to those seen in patients with mTBI, the absence of clear structural damage on conventional neuroimaging in many AHI cases raises questions about the underlying mechanisms.⁸,⁹ Theories involving unknown exposure and subsequent disruption of white matter function have been proposed. Some analyses suggest that the symptoms of AHI could result from the disruption of neuroimmune and neurotransmission mechanisms similar to those affected in patients with TBI.¹⁰,¹¹

Managing post-traumatic headaches involves a multidisciplinary approach including behavioral therapy, physical therapy, oral medications, injectable medications, and interventional procedures. Essentially, these headaches can be treated similarly to the primary headache disorder they resemble.¹² Thus, the post-traumatic migraine can be treated in the acute setting with triptans, NSAIDs, ergot alkaloids, antiemetics, and other therapeutics.¹³,¹⁴ For chronic management, options include beta-blockers, tricyclic antidepressants, CGRP-targeting agents, anti-seizure medications, and many other medications.¹²,¹⁵ Onabotulinum toxin A (OBA) and other medications in the class of botulinum toxins have been particularly effective at reducing the overall frequency and duration of migraines in patients with TBIs,¹⁶,¹⁷ as well as non-TBI-related migraines. OBA results in a blockade of neural stimulation by inhibiting the release of neurotransmitters at the presynaptic terminal.¹⁸,¹⁹ It's thought to reduce the exocytosis of pain mediators (substance P, CGRP) from sensory neurons by cleaving SNAP25.²⁰,²¹ This effect is temporary due to the formation of new synapses, thus patients have to return for repeat injections every 10-12 weeks. Additionally, the number of units of OBA can be optimized to the patient's level of pain during each treatment.

There is limited literature on managing post-AHI headache disorders, but recent experience indicates that using multidisciplinary approaches similar to those used for TBI-related headache disorders may be appropriate.⁶ OBA, and more specifically incobotulinum toxin A (Xeomin brand) has therefore been a commonly used treatment modality in these patient populations in the Military Health System. Many individuals with AHIs from other branches of the government are treated in the MHS though the Secretarial Designee program.

While AHI symptoms might share pathophysiological characteristics with TBIs, there's limited research on Xeomin injections' characteristics in TBI vs. AHI patients, such as treatment frequency and efficacy. This study aims to quantify these similarities and differences in migraine management with Xeomin, potentially improving our understanding of this treatment modality. Migraines can disrupt home, work, and social activities, and treatment can be especially difficult in AHI patients who face limited effective treatment options that are evidence-based, and unique diagnostic challenges. By comparing Xeomin's efficacy in both groups, this study could reveal crucial differences in treatment response, leading to more personalized and effective therapies that align with a holistic healthcare model in medicine. The findings could inform clinical guidelines and improve migraine management in TBI and AHI patients, ultimately reducing the healthcare burden. This research is essential for addressing AHI patients' unmet needs and advancing migraine treatment understanding.