1000 Section - The Effect of Botulinum Toxin-A Injection (BoNTA) Treatment for Persistent Post-Traumatic Headache: A Systematic Review

Objectives : Persistent post-traumatic headache (PTHA) is the most common physical complaint following mild traumatic brain injury. Botulinum toxin type A (BoNTA) is effective for chronic migraine, but its potential for treating PTHA is unclear. This systematic review evaluated the effects of BoNTA on headache frequency, headache severity, quality of life (QoL), and return-to-work status among adults with PTHA.

Design: This review was registered on PROSPERO and followed PRISMA guidelines. MEDLINE, EMBASE + EMBASE Classic, Web of Science, and EBM Reviews were searched from inception to October/November 2024. Eligible studies included randomized and non-randomized interventions or observational designs using any BoNTA formulation to treat PTHA. Two reviewers independently conducted screening, risk of bias assessments, and data extraction, with consensus by a third reviewer. Due to study heterogeneity, findings were synthesized narratively.

Results: Of 901 unique records, seven studies met inclusion criteria (two RCT, four case series, one case report). Migraine was the most common PTHA phenotype, with some mixed phenotypes. Male and military samples predominated; civilian samples had balanced female representation. Four different BoNTA formulations were used (Onabotulinum, Incobotulinum, and Abobotulinum toxin A; one unspecified) with heterogenous dosing and protocols including the PREEMPT protocol. Most BoNTA regimens yielded significant reductions in headache frequency and/or severity compared to baseline. Both RCTs demonstrated significantly greater improvement in headache severity over placebo; one also reported significant reduction in headache days and headaches per week. QoL and return-to-work data were sparse.

Conclusion: Current evidence of BoNTA for PTHA is limited and methodologically heterogeneous but supports its utility in reducing headache frequency and severity, particularly for migraine-type PTHA. The paucity of data on QoL and return-to-work status limits conclusions regarding broader functional benefit. Future research should prioritize adequately powered randomized trials using standardized BoNTA protocols, clear PTHA sub-type phenotyping, and functional outcomes in generalizable populations.