Botulinum Toxin: The Overall Cure for Defective Relaxation?

 

 Buy Article Permissions and Reprints

Introduction

Botulinum toxin, one of the most powerfull biological toxins known, is not only a poison but also a therapeutic agent. Previously known as the cause of botulism - a serious and often fatal form of paralysis acquired through ingestion of contaminated food - the toxin has been found to be of value in the treatment of a variety of neurological and ophthalmological disorders associated with inappropriate muscular contractions or spasms [1]. Strabismus was the first syndrome for which therapy using local injection of botulinum toxin was introduced as an alternative to surgery [2]. Since then, botulinum toxin has also been used successfully for the treatment of other diseases involving involuntary muscle movements. These include blepharospasm, hemifacial spasm, spasmodic torticollis, oromandibular or lingual dystonia, focal dystonias of the hand, neurogenic bladder, and limb spasticity [1]. These disorders are all characterized by extensive efferent activity in cholinergic nerves.

In the past few years, botulinum toxin has been tested or used as therapeutic agent in a variety of gastroenterological disorders. The present article reviews the underlying rationale and the current indications for the use of botulinum toxin in gastroenterology.

References

• 1 National Institute of Health. Consensus conference, November 1990: clinical use of botulinium toxin.  Conn Med. 1991;  55 471-6
  PubMedGoogle Scholar
• 2 Scott A B. Botulinum toxin injections into extraocular muscles as an alternative to strabismus surgery.  Ophthalmology. 1980;  87 1044-9
  CrossrefPubMedGoogle Scholar
• 3 Simpson L L. The origin, structure, and pharmacologic activity of botulinium toxin.  Pharmacol Rev. 1981;  33 155-88
  PubMedGoogle Scholar
• 4 Montecucco C, Schiavo G. Mechanism of action of tetanus and botulinum neurotoxins.  Mol Microbiol. 1994;  13 1-8
  CrossrefPubMedGoogle Scholar
• 5 MacKenzie J, Burnstock G, Dolly J O. The effects of purified botulinum neurotoxin type A on cholinergic, adrenergic and non-adrenergic, atropine-resistant autonomic neuromuscular transmission.  Neurosience. 1982;  7 997-1006
  PubMedGoogle Scholar
• 6 Bigalke H, Habermann E. Blockade of tetanus and botulinum A toxin of postganglionic cholinergic nerve endings in the myenteric plexus.  Naunyn Schmiedebergs Arch Pharmacol. 1980;  312 255-63
  CrossrefPubMedGoogle Scholar
• 7 Wiegand H, Wellhorner H H. The action of botulinum A neurotoxin on the inhibition by antidromic stimulation of the lumbar monosynaptic reflex.  Naunyn Schmiedebergs Arch Pharmacol. 1976;  292 161-5
  CrossrefPubMedGoogle Scholar
• 8 Jankovic J, Brin M F. Therapeutic uses of botulinum toxin.  N Engl J Med. 1991;  324 1186-94
  PubMedGoogle Scholar
• 9 Schwartz K S, Jankovic J. Predicting the response to botulinum toxin injections for the treatment of cervical dystonia (abstract).  Neurology. 1990;  40 382
  PubMedGoogle Scholar
• 10 Siatkowski R M, Tyutyunikov A, Biglan A W, et al. Serum antibody production to botulinum A toxin.  Ophthalmology. 1993;  100 1861-6
  PubMedGoogle Scholar
• 11 Janssens J, Annese V, Vantrappen G. Medical treatment of primary esophageal motility disorders.  Minerva Dietal Gastroenterol. 1990;  36 145-55
  PubMedGoogle Scholar
• 12 Pasricha P J, Ravich W J, Kalloo A N. Effects of intrasphincteric botulinum toxin on the lower esophageal spincter in piglets.  Gastroenterology. 1993;  105 1045-49
  PubMedGoogle Scholar
• 13 Pasricha P J, Ravich W J, Hendrix T R, Kalloo A N. Treatment of achalasia with intrasphincteric injection of botulinum toxin: a pilot trial.  Ann Intern Med. 1994;  121 590-1
  CrossrefPubMedGoogle Scholar
• 14 Pasricha P J, Ravich W J, Hendrix T R, et al. Intrasphincteric botulinum toxin for the treatment of achalasia.  N Engl J Med. 1995;  332 774-8
  CrossrefPubMedGoogle Scholar
• 15 Annese V, Basciani M, Perri F, et al. Controlled trial of botulinum toxin injection versus placebo and pneumatic dilation in achalasia.  Gastroenterology. 1996;  111 1418-24
  CrossrefPubMedGoogle Scholar
• 16 Pasricha P J, Rai R, Ravich W J, et al. Botulinum toxin for achalasia: long-term outcome and predictors of response.  Gastroenterology. 1996;  110 1410-5
  CrossrefPubMedGoogle Scholar
• 17 Cuillière C, Ducrotte P, Zerbib F, et al. Achalasia: outcome of patients treated with intrasphincteric injection of botulinum toxin.  Gut. 1997;  41 87-92
  PubMedGoogle Scholar
• 18 Gordon J M, Eaker E Y. A prospective study of esophageal botulinum toxin injection in high-risk achalasia patients.  Am J Gastroenterol. 1997;  92 1812-7
  PubMedGoogle Scholar
• 19 Fishman V M, Parkman H P, Schiano T D, et al. Symptomatic improvement in achalasia after botulinum toxin injection of the lower esophageal sphincter.  Am J Gastroenterol. 1996;  91 1724-30
  PubMedGoogle Scholar
• 20 Jin H O, Potter G D, Shah A N, et al. Effect of intrasphincteric injection of botulinum toxin on esophageal motility in achalasia (abstract).  Gastroenterology. 1995;  108 A123
  PubMedGoogle Scholar
• 21 Waterfall W E, Tougas G, Fachnie B, et al. Clinical and manometric response to botulinum toxin used as a primary treatment for achalasia (abstract).  Gastroenterology. 1995;  108 A255
  PubMedGoogle Scholar
• 22 Bansal R, Scheiman J M, Barnett J L, et al. Intrasphincteric injection of botulinum toxin for achalasia (abstract).  Gastroenterology. 1995;  108 A54
  PubMedGoogle Scholar
• 23 Greaves R R, Mulcahy H E, Patchett P D, et al. Botulinum toxin in the treatment of achalasia: a promise unfulfilled (abstract).  Gastroenterology. 1996;  110 A123
  PubMedGoogle Scholar
• 24 Birgisson S, Richter J E. Long-term outcome of botulinum toxin in the treatment of achalasia (letter).  Gastroenterology. 1996;  111 1162
  PubMedGoogle Scholar
• 25 Annese V, D'Onofrio V, Andriulli A. Botulinum toxin in long-term therapy for achalasia (letter).  Ann Intern Med. 1998;  128 696
  PubMedGoogle Scholar
• 26 Eaker E Y, Gordon J M, Vogel S B. Untoward effects of esophageal botulinum toxin injection in the treatment of achalasia.  Dig Dis Sci. 1997;  42 724-7
  CrossrefPubMedGoogle Scholar
• 27 Vantrappen G, Hellemans J. Treatment of achalasia and related motor disorders.  Gastroenteroloy. 1980;  79 144-54
  PubMedGoogle Scholar
• 28 Katz P. Achalasia: two effective treatment options - let the patient decide.  Am J Gastroenterol. 1994;  89 969-70
  PubMedGoogle Scholar
• 29 Malthaner R A, Todd T R, Miller L, Pearson F G. Long-term results in surgically managed esophageal achalasia.  Ann Thorac Surg. 1994;  58 1343-6
  PubMedGoogle Scholar
• 30 Schwartz H M, Cahow C E, Traube M. Outcome after perforation sustained during pneumatic dilatation for achalasia.  Dig Dis Sci. 1993;  38 1409-13
  CrossrefPubMedGoogle Scholar
• 31 Abid S, Champion G, Richter J E. Treatment of achalasia: the best of both worlds.  Am J Gastroenterol. 1994;  89 979-85
  PubMedGoogle Scholar
• 32 Panaccione R, Gregor J C, Reynolds R PE, Preiksaitis H G. A cost minimization analysis of intrasphincteric botulinum toxin versus pneumatic dilatation in patients with achalasia (abstract).  Gastroenterology. 1997;  112 A250
  PubMedGoogle Scholar
• 33 Choudry U, Boyce H W. A prospective study of the efficacy of botulinum toxin A (BTX) in patients with epiphrenic diverticula (abstract).  Am J Gastroenterol. 1996;  91 1885
  PubMedGoogle Scholar
• 34 Wehrmann T, Kokabpick H, Jacobi V, et al. Endoskopische Botulinus Toxin Injektion zur Behandlung von “Hochrisiko”-Achalasie-Patienten (abstract).  Z Gastroenterol. 1998;  36 726
  PubMedGoogle Scholar
• 35 Annese V, Basciani M, Lombardi G, et al. Perendoscopic injection of botulinum toxin is effective in achalasia after failure of myotomy or pneumatic dilation.  Gastrointest Endosc. 1996;  44 461-5
  PubMedGoogle Scholar
• 36 Miller L S, Parkman H P, Schiano T D, et al. Treatment of symptomatic nonachalasia esophageal motility disorders with botulinum toxin injection at the lower esophageal sphincter.  Dig Dis Sci. 1996;  41 2025-31
  CrossrefPubMedGoogle Scholar
• 37 Cassidy M J, Schiano T D, Adrian A L, et al. Botulinum toxin injection for the treatment of symptomatic diffuse esophageal spasm (abstract).  Am J Gastroenterol. 1996;  91 1884
  PubMedGoogle Scholar
• 38 Sherman S, Ruffolo T A, Hawes R H, Lehman G A. Complications of endoscopic sphincterotomy.  Gastroenterology. 1991;  101 1068-75
  CrossrefPubMedGoogle Scholar
• 39 Guelrud M, Mendoza S, Viera L, et al. Somatostatin prevents acute pancreatitis after pancreatic duct sphincter hydrostatic balloon dilation in patients with idiopathic recurrent pancreatitis.  Gastrointest Endosc. 1991;  37 44-7
  CrossrefPubMedGoogle Scholar
• 40 Goff J S. Common bile duct sphincter of Oddi stenting in patients with suspected sphincter dysfunction.  Am J Gastroenterol. 1995;  90 586-9
  PubMedGoogle Scholar
• 41 Pasricha P J, Miskovsky E P, Kalloo A N. Intrasphincteric injection of botulinum toxin for suspected sphincter of Oddi dysfunction.  Gut. 1994;  35 1319-21
  PubMedGoogle Scholar
• 42 Wehrmann T, Seifert H, Seipp M, et al. Endoscopic injection of botulinum toxin for biliary sphincter of Oddi dysfunction.  Endoscopy. 1998;  30 702-7
  PubMedGoogle Scholar
• 43 Muehldorfer S M, Hahn E G, Ell C. Botulinum toxin injection as a diagnostic tool for verification of sphincter of Oddi dysfunction causing recurrent pancreatitis.  Endoscopy. 1997;  29 120-4
  PubMedGoogle Scholar
• 44 Arabi Y, Alexander-Williams J, Keighley M RB. Anal pressures in hemorrhoids and anal fissure.  Ann J Surg. 1977;  134 608-10
  PubMedGoogle Scholar
• 45 Notham B J, Schuster M M. Internal anal sphincter derangement with anal fissure.  Gastroenterology. 1974;  67 216-30
  PubMedGoogle Scholar
• 46 Gibbons C P, Read N W. Anal hypertonia in fissures: cause or effect?.  Br J Surg. 1986;  73 443-5
  CrossrefPubMedGoogle Scholar
• 47 Mason P F, Watkins M JG, Hall H S, Hall A W. The management of chronic fissure in ano with botulinum toxin.  J R Coll Surg Edinb. 1996;  41 235-8
  PubMedGoogle Scholar
• 48 Weaver R M, Ambrose N S, Alexander-Williams J, Keighley M RB. Manual dilatation of the anus vs. lateral sphincterotomy in the treatment of chronic fissure in ano: results of a prospective, randomized, clinical trial.  Dis Colon Rectum. 1987;  30 420-3
  PubMedGoogle Scholar
• 49 Maria G, Cassetta E, Daniele G, et al. A comparison of botulinum toxin and saline for the treatment of chronic anal fissure.  N Engl J Med. 1998;  338 217-20
  CrossrefPubMedGoogle Scholar
• 50 Gorfine S R. Topical nitroglycerin therapy for anal fissure and ulcers.  N Engl J Med. 1995;  333 1156-7
  CrossrefPubMedGoogle Scholar
• 51 Watson S J, Kamm M A, Nichols R J, Phillips R KS. Topical glyceryl trinitrate in the treatment of chronic anal fissure.  Br J Surg. 1996;  83 771-5
  PubMedGoogle Scholar
• 52 Lund J N, Armitage N C, Scholefield J H. Use of glyceryl trinitrate ointment in the treatment of anal fissure.  Br J Surg. 1996;  83 776-7
  PubMedGoogle Scholar
• 53 Klosterhalften B, Vogel P, Rixen H, Mittermayer C. Topography of the inferior rectal artery: a possible cause of chronic primary anal fissure.  Dis Colon Rectum. 1989;  32 43-52
  PubMedGoogle Scholar
• 54 Jost W H. One hundred cases of anal fissure treated with botulinum toxin.  Dis Colon Rectum. 1997;  40 1029-32
  CrossrefPubMedGoogle Scholar
• 55 Gui D, Cassetta E, Anastasio G, et al. Botulinum toxin for chronic anal fissure.  Lancet. 1994;  344 1127-8
  CrossrefPubMedGoogle Scholar
• 56 Birkenfeld S, Ron Y, Rozen A, et al. Treatment of anal fissure with botulinum toxin injections (abstract).  Gastroenterology. 1997;  112 A4
  PubMedGoogle Scholar
• 57 Hallan R I, Williams N S, Melling J, et al. Treatment of anismus in intractable constipation with botulinum A toxin.  Lancet. 1988;  2 714-7
  PubMedGoogle Scholar
• 58 Enck P. Biofeedback training in disordered defecation: a critical review.  Dig Dis Sci. 1993;  38 1953-60
  CrossrefPubMedGoogle Scholar
• 59 Langer J C, Birnbaum E. Preliminary experience with intrasphincteric botulinum toxin for persistent constipation.  J Pediatr Surg. 1997;  32 1059-6
  CrossrefPubMedGoogle Scholar

M. ThumshirnM.D. 

Universitätsspital Zürich

Dept. für Innere Medizin

Abt. Gastroenterologie

Rämistrasse 100, 8091 Zürich, Switzerland

Phone: + 41-1-2554503

Email: klinthum@usz.unizh.ch