Post-craniotomy headache and botulinum toxin A: A systematic review of case reports and case series

Abstract

Background Post-craniotomy headache (PCH) is a common, often debilitating complication with limited treatment options and unclear pathophysiology. While botulinum toxin A (BoNT-A) is effective for various headache disorders, its use in PCH is underexplored. This systematic review examines case reports and series on BoNT-A's efficacy and safety for PCH. Methods A systematic search of PubMed, Scopus, and Web of Science was conducted in February 2025 using relevant keywords. Case reports and series on BoNT-A treatment for PCH were included, while unrelated studies, reviews, and incomplete abstracts were excluded. Data on patient characteristics, treatment protocols, efficacy, and adverse events were extracted. Results Five case series published up to 2025 report on 15 patients from France, Canada, and the United States. Each study enrolled only three or four patients, all with persistent PCH unresponsive to standard analgesics. BoNT-A regimens differed widely, ranging from 15 to 165 U, and included single versus repeated sessions, as well as injection sites such as the temporalis muscle, incision margins, and cranial suture lines, highlighting the lack of a standardized protocol. Eleven patients achieved 75–100% pain relief within 10–15 days, with therapeutic effects persisting for several weeks to over 5 years. Many also demonstrated improvements in daily functioning and a reduction in analgesic consumption. No serious adverse events were reported, supporting BoNT-A as a safe and promising treatment for PCH. Conclusion BoNT-A is a well-tolerated and effective option for patients with refractory PCH, offering substantial pain relief and functional improvement. However, given the reliance on small-scale studies, larger clinical trials are needed to confirm its efficacy and establish standardized treatment protocols.