A proposal to prevent the "Mephisto sign" side effect of botulinum toxin type A injection in chronic migraine
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Updated: May 6, 2026

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Published on: November 1, 2024
Eunae S Cho1, Jae Young Hwang, Seong Taek Kim
1Department of Orofacial Pain and Oral Medicine, College of Dentistry, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea. k8756050@hotmail.com.
Abstract:
Botulinum toxin type A (BoNT-A) has been reported as an effective treatment for chronic migraine. When BoNT-A is injected on the frontalis muscle for chronic migraine, an unexpected clinical side effect called the "Mephisto sign" may occur. The aim of this article is to propose a method to eliminate or prevent the Mephisto sign side effect. A 25-year-old female patient visited the hospital and was diagnosed with chronic migraine. A total of 155 U of BoNT-A was injected into 31 sites. 2-weeks later, and the patient developed the Mephisto sign. An additional 2-U dose was administered bilaterally to the lateral-most point of the frontalis muscles, and the eyebrow morphology returned to normal within 2-3 weeks. We propose that the development of the Mephisto sign may be prevented with an additional BoNT-A injection of 2-4 U bilaterally to the lateral most point of the frontalis muscles during the primary injection process.
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