Refractory Chronic Migraine Therapy with Botulinum Toxin A

  • Reto AgostiEmail author
Part of the Headache book series (HEAD)


Once diagnosis of a migraine is made (including imaging studies to rule out secondary headaches, criterion E of ICHD 1.1 or 1.2), no further diagnostic workup is needed before initiating a treatment with Botox. However, for Botox treatment of migraine, a diagnosis of “chronic migraine” (CM) is required according to the PREEMPT protocols. The most reliable tool is a patient headache diary in which the headache days can be distinguished between days with migraine and days with non-migraine headaches. Neurological exam may reveal tender points in those pericranial muscles that may receive additional dosages according to the “follow the pain” paradigm (temporalis, occipitalis, and trapezius muscles). Oral anticoagulation needs to be asked although full anticoagulation is not an absolute contraindication.


Botulinum Toxin Chronic Migraine Diagnostic Workup Trapezius Muscle Episodic Migraine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Suggested Reading

  1. 1.
    Antonucci F, Rossi C, Gianfranceschi L et al (2008) Long-distance retrograde effects of botulinum neurotoxin A. J Neurosci 28:3689–3696PubMedCrossRefGoogle Scholar
  2. 2.
    Ashkenazi A (2010) Botulinum toxin type A for chronic migraine. Curr Neurol Neurosci Rep 10:140–146PubMedCrossRefGoogle Scholar
  3. 3.
    Aurora SK, Dodick DW, Turkel CC et al (2010) OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia 30:793–803PubMedCrossRefGoogle Scholar
  4. 4.
    Aurora SK, Gawel M, Brandes JL et al (2007) Botulinum toxin type a prophylactic treatment of episodic migraine: a randomized, double-blind, placebo-controlled exploratory study. Headache 47:486–499PubMedGoogle Scholar
  5. 5.
    Binder WJ, Brin MF, Blitzer A et al (2000) Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study. Otolaryngol Head Neck Surg 123:669–676PubMedCrossRefGoogle Scholar
  6. 6.
    Blumenfeld A, Silberstein SD, Dodick DW et al (2010) Method of injection of onabotulinumtoxinA for chronic migraine: a safe, well-tolerated, and effective treatment paradigm based on the PREEMPT clinical program. Headache 50:1406–1418PubMedCrossRefGoogle Scholar
  7. 7.
    Brin MF (1997) Botulinum toxin: chemistry, pharmacology, toxicity, and immunology. Muscle Nerve Suppl 6:S146–S168PubMedCrossRefGoogle Scholar
  8. 8.
    Bumb A, Wetzel S, Agosti R (2013) Patients profiling for Botox® (onabotulinumtoxin A) treatment for migraine: a look at white matter lesions in the MRI as a potential marker. Springerplus 2:377PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Cui M, Khanijou S, Rubino J et al (2004) Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain 107:125–133PubMedCrossRefGoogle Scholar
  10. 10.
    Diener HC, Dodick DW, Aurora SK et al (2010) OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia 30:804–814PubMedCrossRefGoogle Scholar
  11. 11.
    Dodick DW, Mauskop A, Elkind AH et al (2005) Botulinum toxin type A for the prophylaxis of chronic daily headache: subgroup analysis of patients not receiving other prophylactic medications: a randomized double-blind, placebo-controlled study. Headache 45:315–324PubMedCrossRefGoogle Scholar
  12. 12.
    Dodick DW, Turkel CC, Degryse RE et al (2010) OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache 50:921–936PubMedCrossRefGoogle Scholar
  13. 13.
    Dolly O (2003) Synaptic transmission: inhibition of neurotransmitter release by botulinum toxins. Headache 43(Suppl 1):S16–S24PubMedCrossRefGoogle Scholar
  14. 14.
    Dowson AJ, Kilminster SG, Salt R (2008) Clinical profile of botulinum toxin A in patients with chronic headaches and cervical dystonia: a prospective, open-label, longitudinal study conducted in a naturalistic clinical practice setting. Drugs R D 9:147–158PubMedCrossRefGoogle Scholar
  15. 15.
    Durham PL, Cady R, Cady R (2004) Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy. Headache 44:35–42PubMedCrossRefGoogle Scholar
  16. 16.
    Eross EJ, Gladstone JP, Lewis S et al (2005) Duration of migraine is a predictor for response to botulinum toxin type A. Headache 45:308–314PubMedCrossRefGoogle Scholar
  17. 17.
    Evers S, Vollmer-Haase J, Schwaag S et al (2004) Botulinum toxin A in the prophylactic treatment of migraine – a randomized, double-blind, placebo-controlled study. Cephalalgia 24:838–843PubMedCrossRefGoogle Scholar
  18. 18.
    FDA approves Botox to treat chronic migraine (2013) Available at: Accessed 11 May 2013
  19. 19.
    Headache Classification Subcommittee of the International Headache Society (2004) The international classification of headache disorders: 2nd edition. Cephalalgia 24(Suppl 1):9–160Google Scholar
  20. 20.
    Jackson JL, Kuriyama A, Hayashino Y (2012) Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: a meta-analysis. JAMA 307:1736–1745PubMedCrossRefGoogle Scholar
  21. 21.
    Mathew NT, Frishberg BM, Gawel M et al (2005) Botulinum toxin type A (BOTOX) for the prophylactic treatment of chronic daily headache: a randomized, double-blind, placebo-controlled trial. Headache 45:293–307PubMedCrossRefGoogle Scholar
  22. 22.
    McMahon HT, Foran P, Dolly JO et al (1992) Tetanus toxin and botulinum toxins type A and B inhibit glutamate, gamma-aminobutyric acid, aspartate, and met-enkephalin release from synaptosomes. Clues to the locus of action. J Biol Chem 267:21338–21343PubMedGoogle Scholar
  23. 23.
    Ondo WG, Gollomp S, Galvez-Jimenez N (2005) A pilot study of botulinum toxin A for headache in cervical dystonia. Headache 45:1073–1077PubMedCrossRefGoogle Scholar
  24. 24.
    Ondo WG, Vuong KD, Derman HS (2004) Botulinum toxin A for chronic daily headache: a randomized, placebo-controlled, parallel design study. Cephalalgia 24:60–65PubMedCrossRefGoogle Scholar
  25. 25.
    Ranoux D, Attal N, Morain F et al (2008) Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain. Ann Neurol 64:274–283PubMedCrossRefGoogle Scholar
  26. 26.
    Relja M, Poole AC, Schoenen J et al (2007) A multicentre, double-blind, randomized, placebo-controlled, parallel group study of multiple treatments of botulinum toxin type A (BoNTA) for the prophylaxis of episodic migraine headaches. Cephalalgia 27:492–503PubMedCrossRefGoogle Scholar
  27. 27.
    Shapiro RL, Hatheway C, Swerdlow DL (1998) Botulism in the United States: a clinical and epidemiologic review. Ann Intern Med 129:221–228PubMedCrossRefGoogle Scholar
  28. 28.
    Silberstein S, Mathew N, Saper J et al (2000) Botulinum toxin type A as a migraine preventive treatment. For the BOTOX Migraine Clinical Research Group. Headache 40:445–450PubMedCrossRefGoogle Scholar
  29. 29.
    Silberstein SD, Stark SR, Lucas SM et al (2005) Botulinum toxin type A for the prophylactic treatment of chronic daily headache: a randomized, double-blind, placebo-controlled trial. Mayo Clin Proc 80:1126–1137PubMedCrossRefGoogle Scholar
  30. 30.
    Smuts JA, Schultz D, Barnard A (2004) Mechanism of action of botulinum toxin type A in migraine prevention: a pilot study. Headache 44:801–805PubMedCrossRefGoogle Scholar
  31. 31.
    Turton K, Chaddock JA, Acharya KR (2002) Botulinum and tetanus neurotoxins: structure, function and therapeutic utility. Trends Biochem Sci 27:552–558PubMedCrossRefGoogle Scholar
  32. 32.
    Winner PK, Sadowsky CH, Martinez WC et al (2012) Concurrent onabotulinumtoxinA treatment of cervical dystonia and concomitant migraine. Headache 52:1219–1225PubMedCrossRefGoogle Scholar
  33. 33.
    Wollmer MA, De Boer C, Kalaka N et al (2012) Facing depression with botulinum toxin: a randomized controlled trial. J Psychiatr Res 46:574–581PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Kopfwehzentrum Hirslanden Zürich – Headache CenterZollikonSwitzerland

Personalised recommendations