Advertisement

Achalasia pp 31-38 | Cite as

Botulinum Toxin for Achalasia

  • Hiroshi Mashimo

Abstract

Botulinum neurotoxin (BoNT) is being used for the treatment of various conditions including upper motor neuron syndrome, hyperhidrosis, various spastic disorders including blepharospasm, hemifacial spasm, neurogenic detrusor over-activity, focal dystonias, strabismus, vaginismus, and achalasia. Emerging uses for botulinum toxin type A include chronic musculoskeletal pain, vocal cord dysfunction, and allergic rhinitis. The goal of this chapter is to describe the use of BoNT in the treatment of patients with achalasia, focusing on the clinical evidence along with a description of the side-effects and contraindications.

Keywords

Achalasia Botulinum toxin injection Pathophysiology Mechanism of action Outcomes 

References

  1. 1.
    Pasricha PJ, Ravich WJ, Kalloo AN. Botulinum toxin for achalasia. Lancet. 1993;341(8839):244–5.CrossRefPubMedGoogle Scholar
  2. 2.
    Mikaeli J, Veisari AK, Fazlollahi N, Mehrabi N, Soleimani HA, Shirani S, et al. Ethanolamine oleate versus botulinum toxin in the treatment of idiopathic achalasia. Ann Gastroenterol. 2015;28(2):229–35.PubMedCentralPubMedGoogle Scholar
  3. 3.
    Erbguth FJ. From poison to remedy: the chequered history of botulinum toxin. J Neural Transm. 2008;115(4):559–65.CrossRefPubMedGoogle Scholar
  4. 4.
    Tessmer Snipe P, Sommer H. Studies on botulinus toxin: 3. Acid precipitation of botulinus toxin. J Infect Dis. 1928;43(2):152–60.CrossRefGoogle Scholar
  5. 5.
    Burgen AS, Dickens F, Zatman LJ. The action of botulinum toxin on the neuro-muscular junction. J Physiol. 1949;109(1–2):10–24.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Melling J, Hambleton P, Shone CC. Clostridium botulinum toxins: nature and preparation for clinical use. Eye. 1988;2(Pt 1):16–23.CrossRefPubMedGoogle Scholar
  7. 7.
    Lacy BE, Weiser K, Kennedy A. Botulinum toxin and gastrointestinal tract disorders: panacea, placebo, or pathway to the future? Gastroenterol Hepatol. 2008;4(4):283–95.Google Scholar
  8. 8.
    Barr JR, Moura H, Boyer AE, Woolfitt AR, Kalb SR, Pavlopoulos A, et al. Botulinum neurotoxin detection and differentiation by mass spectrometry. Emerg Infect Dis. 2005;11(10):1578–83.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Ishikawa H, Mitsui Y, Yoshitomi T, Mashimo K, Aoki S, Mukuno K, et al. Presynaptic effects of botulinum toxin type A on the neuronally evoked response of albino and pigmented rabbit iris sphincter and dilator muscles. Jpn J Ophthalmol. 2000;44(2):106–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Aoki KR. Evidence for antinociceptive activity of botulinum toxin type A in pain management. Headache. 2003;43 Suppl 1:S9–15.CrossRefPubMedGoogle Scholar
  11. 11.
    Kim YJ, Kim JH, Lee KJ, Choi MM, Kim YH, Rhie GE, et al. Botulinum neurotoxin type A induces TLR2-mediated inflammatory responses in macrophages. PLoS One. 2015;10(4), e0120840.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Dressler D, Saberi FA, Barbosa ER. Botulinum toxin: mechanisms of action. Arq Neuropsiquiatr. 2005;63(1):180–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Park JH, Choi E, Park H, Lee YH. A direct inhibitory effect of botulinum toxin type A on antral circular muscle contractility of guinea pig. Yonsei Med J. 2012;53(5):968–73.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    James AN, Ryan JP, Parkman HP. Inhibitory effects of botulinum toxin on pyloric and antral smooth muscle. Am J Physiol Gastrointest Liver Physiol. 2003;285(2):G291–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Ma J, Shen J, Lee CA, Elsaidi GA, Smith TL, Walker FO, et al. Gene expression of nAChR, SNAP-25 and GAP-43 in skeletal muscles following botulinum toxin A injection: a study in rats. J Orthop Res. 2005;23(2):302–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Shen J, Ma J, Lee C, Smith BP, Smith TL, Tan KH, et al. How muscles recover from paresis and atrophy after intramuscular injection of botulinum toxin A: study in juvenile rats. J Orthop Res. 2006;24(5):1128–35.CrossRefPubMedGoogle Scholar
  17. 17.
    Foran PG, Davletov B, Meunier FA. Getting muscles moving again after botulinum toxin: novel therapeutic challenges. Trends Mol Med. 2003;9(7):291–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Bassotti G, D’Onofrio V, Battaglia E, Fiorella S, Dughera L, Iaquinto G, et al. Treatment with botulinum toxin of octo-nonagerians with oesophageal achalasia: a two-year follow-up study. Aliment Pharmacol Ther. 2006;23(11):1615–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Goschel H, Wohlfarth K, Frevert J, Dengler R, Bigalke H. Botulinum A toxin therapy: neutralizing and nonneutralizing antibodies – therapeutic consequences. Exp Neurol. 1997;147(1):96–102.CrossRefPubMedGoogle Scholar
  20. 20.
    Coskun H, Duran Y, Dilege E, Mihmanli M, Seymen H, Demirkol MO. Effect on gastric emptying and weight reduction of botulinum toxin-A injection into the gastric antral layer: an experimental study in the obese rat model. Obes Surg. 2005;15(8):1137–43.CrossRefPubMedGoogle Scholar
  21. 21.
    Zhao CM, Hayakawa Y, Kodama Y, Muthupalani S, Westphalen CB, Andersen GT, et al. Denervation suppresses gastric tumorigenesis. Sci Transl Med. 2014;6(250):250ra115.PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Kalloo AN, Pasricha PJ. Therapy of sphincter of Oddi dysfunction. Gastrointest Endosc Clin N Am. 1996;6(1):117–25.PubMedGoogle Scholar
  23. 23.
    Trzcinski R, Dziki A, Tchorzewski M. Injections of botulinum A toxin for the treatment of anal fissures. Eur J Surg. 2002;168(12):720–3.CrossRefPubMedGoogle Scholar
  24. 24.
    Dressler D, Benecke R. Pharmacology of therapeutic botulinum toxin preparations. Disabil Rehabil. 2007;29(23):1761–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Gioltzoglou T, Cordivari C, Lee PJ, Hanna MG, Lees AJ. Problems with botulinum toxin treatment in mitochondrial cytopathy: case report and review of the literature. J Neurol Neurosurg Psychiatry. 2005;76(11):1594–6.PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Eaker EY, Gordon JM, Vogel SB. Untoward effects of esophageal botulinum toxin injection in the treatment of achalasia. Dig Dis Sci. 1997;42(4):724–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Dolimbek BZ, Aoki KR, Steward LE, Jankovic J, Atassi MZ. Mapping of the regions on the heavy chain of botulinum neurotoxin A (BoNT/A) recognized by antibodies of cervical dystonia patients with immunoresistance to BoNT/A. Mol Immunol. 2007;44(5):1029–41.CrossRefPubMedGoogle Scholar
  28. 28.
    Atassi MZ, Jankovic J, Steward LE, Aoki KR, Dolimbek BZ. Molecular immune recognition of botulinum neurotoxin B. The light chain regions that bind human blocking antibodies from toxin-treated cervical dystonia patients. Antigenic structure of the entire BoNT/B molecule. Immunobiology. 2012;217(1):17–27.CrossRefPubMedGoogle Scholar
  29. 29.
    Hanna PA, Jankovic J, Vincent A. Comparison of mouse bioassay and immunoprecipitation assay for botulinum toxin antibodies. J Neurol Neurosurg Psychiatry. 1999;66(5):612–6.PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Rosales RL, Bigalke H, Dressler D. Pharmacology of botulinum toxin: differences between type A preparations. Eur J Neurol. 2006;13 Suppl 1:2–10.CrossRefPubMedGoogle Scholar
  31. 31.
    Annese V, Bassotti G, Coccia G, D’Onofrio V, Gatto G, Repici A, et al. Comparison of two different formulations of botulinum toxin A for the treatment of oesophageal achalasia. The Gismad Achalasia Study Group. Aliment Pharmacol Ther. 1999;13(10):1347–50.CrossRefPubMedGoogle Scholar
  32. 32.
    Walzer N, Hirano I. Achalasia. Gastroenterol Clin N Am. 2008;37(4):807–25, viii.CrossRefGoogle Scholar
  33. 33.
    Annese V, Bassotti G, Coccia G, Dinelli M, D’Onofrio V, Gatto G, et al. A multicentre randomised study of intrasphincteric botulinum toxin in patients with oesophageal achalasia. GISMAD Achalasia Study Group. Gut. 2000;46(5):597–600.PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Dughera L, Battaglia E, Maggio D, Cassolino P, Mioli PR, Morelli A, et al. Botulinum toxin treatment of oesophageal achalasia in the old old and oldest old: a 1-year follow-up study. Drugs Aging. 2005;22(9):779–83.CrossRefPubMedGoogle Scholar
  35. 35.
    Allescher HD, Storr M, Seige M, Gonzales-Donoso R, Ott R, Born P, et al. Treatment of achalasia: botulinum toxin injection vs. pneumatic balloon dilation. A prospective study with long-term follow-Up. Endoscopy. 2001;33(12):1007–17.CrossRefPubMedGoogle Scholar
  36. 36.
    Zarate N, Mearin F, Baldovino F, Armengol JR, Malagelada JR. Achalasia treatment in the elderly: is botulinum toxin injection the best option? Eur J Gastroenterol Hepatol. 2002;14(3):285–90.CrossRefPubMedGoogle Scholar
  37. 37.
    Leyden JE, Moss AC, MacMathuna P. Endoscopic pneumatic dilation versus botulinum toxin injection in the management of primary achalasia. Cochrane Database Syst Rev. 2006;4, CD005046.PubMedGoogle Scholar
  38. 38.
    Campos GM, Vittinghoff E, Rabl C, Takata M, Gadenstatter M, Lin F, et al. Endoscopic and surgical treatments for achalasia: a systematic review and meta-analysis. Ann Surg. 2009;249(1):45–57.CrossRefPubMedGoogle Scholar
  39. 39.
    Mikaeli J, Bishehsari F, Montazeri G, Mahdavinia M, Yaghoobi M, Darvish-Moghadam S, et al. Injection of botulinum toxin before pneumatic dilatation in achalasia treatment: a randomized-controlled trial. Aliment Pharmacol Ther. 2006;24(6):983–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Andrews CN, Anvari M, Dobranowski J. Laparoscopic Heller’s myotomy or botulinum toxin injection for management of esophageal achalasia. Patient choice and treatment outcomes. Surg Endosc. 1999;13(8):742–6.CrossRefPubMedGoogle Scholar
  41. 41.
    Zaninotto G, Vergadoro V, Annese V, Costantini M, Costantino M, Molena D, et al. Botulinum toxin injection versus laparoscopic myotomy for the treatment of esophageal achalasia: economic analysis of a randomized trial. Surg Endosc. 2004;18(4):691–5.CrossRefPubMedGoogle Scholar
  42. 42.
    Vaezi MF, Pandolfino JE, Vela MF. ACG clinical guideline: diagnosis and management of achalasia. Am J Gastroenterol. 2013;108(8):1238–49, quiz 50.CrossRefPubMedGoogle Scholar
  43. 43.
    Spechler SJ. American gastroenterological association medical position statement on treatment of patients with dysphagia caused by benign disorders of the distal esophagus. Gastroenterology. 1999;117(1):229–33.CrossRefPubMedGoogle Scholar
  44. 44.
    Richardson WS, Willis GW, Smith JW. Evaluation of scar formation after botulinum toxin injection or forced balloon dilation to the lower esophageal sphincter. Surg Endosc. 2003;17(5):696–8.CrossRefPubMedGoogle Scholar
  45. 45.
    Bloomston M, Fraiji E, Boyce Jr HW, Gonzalvo A, Johnson M, Rosemurgy AS. Preoperative intervention does not affect esophageal muscle histology or patient outcomes in patients undergoing laparoscopic Heller myotomy. J Gastrointest Surg. 2003;7(2):181–8; discussion 8–90.CrossRefPubMedGoogle Scholar
  46. 46.
    Cowgill SM, Villadolid DV, Al-Saadi S, Rosemurgy AS. Difficult myotomy is not determined by preoperative therapy and does not impact outcome. JSLS. 2007;11(3):336–43.PubMedCentralPubMedGoogle Scholar
  47. 47.
    Srinivasan R, Vela M, Tutuian R, Katz P, Castell D. Prior botulinum toxin injection may compromise outcome of pneumatic dilatation in achalasia. Am J Gastroenterol. 2000;95(9):2436–7.CrossRefGoogle Scholar
  48. 48.
    Smith CD, Stival A, Howell DL, Swafford V. Endoscopic therapy for achalasia before Heller myotomy results in worse outcomes than heller myotomy alone. Ann Surg. 2006;243(5):579–84; discussion 84–86.PubMedCentralCrossRefPubMedGoogle Scholar
  49. 49.
    Portale G, Costantini M, Rizzetto C, Guirroli E, Ceolin M, Salvador R, et al. Long-term outcome of laparoscopic Heller-Dor surgery for esophageal achalasia: possible detrimental role of previous endoscopic treatment. J Gastrointest Surg. 2005;9(9):1332–9.CrossRefPubMedGoogle Scholar
  50. 50.
    Prakash C, Freedland KE, Chan MF, Clouse RE. Botulinum toxin injections for achalasia symptoms can approximate the short term efficacy of a single pneumatic dilation: a survival analysis approach. Am J Gastroenterol. 1999;94(2):328–33.CrossRefPubMedGoogle Scholar
  51. 51.
    Yeung JC, Finley C, Hanna WC, Miller L, Ferri L, Urbach DR, et al. Treatment choices and outcomes of patients with manometrically diagnosed achalasia. Dis Esophagus. 2015. Early online doi: 10.1111/dote.12348
  52. 52.
    Robertson CS, Fellows IW, Mayberry JF, Atkinson M. Choice of therapy for achalasia in relation to age. Digestion. 1988;40(4):244–50.CrossRefPubMedGoogle Scholar
  53. 53.
    Mikaeli J, Yaghoobi M, Montazeri G, Ansari R, Bishehsari F, Malekzadeh R. Efficacy of botulinum toxin injection before pneumatic dilatation in patients with idiopathic achalasia. Dis Esophagus. 2004;17(3):213–7.CrossRefPubMedGoogle Scholar
  54. 54.
    Pasricha PJ, Rai R, Ravich WJ, Hendrix TR, Kalloo AN. Botulinum toxin for achalasia: long-term outcome and predictors of response. Gastroenterology. 1996;110(5):1410–5.CrossRefPubMedGoogle Scholar
  55. 55.
    Neubrand M, Scheurlen C, Schepke M, Sauerbruch T. Long-term results and prognostic factors in the treatment of achalasia with botulinum toxin. Endoscopy. 2002;34(7):519–23.CrossRefPubMedGoogle Scholar
  56. 56.
    Marjoux S, Brochard C, Roman S, Gincul R, Pagenault M, Ponchon T, et al. Botulinum toxin injection for hypercontractile or spastic esophageal motility disorders: may high-resolution manometry help to select cases? Dis Esophagus. 2014. Early online doi: 10.1111/dote.12282

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of GastroenterologyBoston VA Healthcare System, Harvard Medical SchoolBostonUSA

Personalised recommendations