, Volume 29, Issue 4, pp 500–508 | Cite as

The Use of Botulinum Toxin Injections to Manage Drooling in Amyotrophic Lateral Sclerosis/Motor Neurone Disease: A Systematic Review

  • Nina SquiresEmail author
  • Miles Humberstone
  • Adrian Wills
  • Antony Arthur
Original Article


Difficulty in managing oral secretions is commonly experienced by patients with amyotrophic lateral sclerosis (ALS)/motor neurone disease (MND) and associated bulbar weakness including dysphagia. There are no definitive evidence-based treatment guidelines to manage the distressing symptom of drooling. We reviewed the evidence for the effectiveness of botulinum toxin injections to reduce saliva in ALS/MND. The search strategy was conducted in four stages: (1) electronic search of relevant databases, (2) hand searches of all international ALS/MND symposium journals, (3) email request to MND care centres in the UK and Ireland, and (4) hand searching of reference lists. All studies were critically appraised and relevant data extracted. Botulinum toxin type A and type B were analysed separately. Due to heterogeneity, it was not possible to calculate a pooled estimate of effect. Twelve studies met the inclusion criteria (9 for type A and 3 for type B). Only two randomised controlled trials were identified. Study sample sizes were small with a mean of 12.5 subjects. The most frequently reported outcomes were weight of cotton rolls and number of tissues used. All studies claimed the intervention tested was effective, but only seven studies (4 for type A and 3 for type B) reported statistically significant differences. Although there is evidence to suggest that botulinum toxin B can reduce drooling, the evidence base is limited by a lack of randomized controlled trials. Evidence to support the use of botulinum toxin A is weaker. Larger trials will help remove the uncertainty practitioners face in treating this disabling symptom.


Deglutition Deglutition disorders Saliva Botulinum toxin injections Motor neurone disease Amyotrophic lateral sclerosis 



We thank Sheila Lloyd, Librarian at the Motor Neurone Disease Association, and Julia Johnson, Specialist Speech and Language Therapist at Kings College Hospital, London, for assisting in identifying relevant papers, and Nicola Darlington, Librarian at the University of Nottingham, for refining the search strategy.

Conflict of interest

The authors have no conflicts of interest to disclose.


  1. 1.
    Verma A, Steele J. Botulinum toxin improves sialorrhea and quality of living in bulbar amyotrophic lateral sclerosis. Muscle Nerve. 2006;34:235–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Yorkston K, Miller R, Strand E. Management of speech and swallowing in degenerative diseases. Austin, TX: Pro-Ed; 1999.Google Scholar
  3. 3.
    Easterling C, Antinoja J, Cashin S, Barkhaus PE. Changes in tongue pressure, pulmonary function, and salivary flow in patients with amyotrophic lateral sclerosis. Dysphagia. 2013;28:217–25.PubMedCrossRefGoogle Scholar
  4. 4.
    Miller RG, Rosenberg JA, Gelinas DF, Mitsumoto H, Newman D, Sufit R, Borasio GD, Bradley WG, Bromberg BM, Brooks BR, Kasarskis EJ, Munsat TL, Oppenheimer EA. Practice parameter: the care of the patient with amyotrophic lateral sclerosis (an evidence-based review). Neurology. 1999;52:1311–23.PubMedCrossRefGoogle Scholar
  5. 5.
    Andersen PM, Borasio GD, Dengler R, Hardiman O, Kollewe K, Leigh PN, Pradat PF, Silani V, Tomkin B. EFNS task force on management of amyotrophic lateral sclerosis: guidelines for diagnosing and clinical care of patients and relatives. Eur J Neurol. 2005;12:921–38.PubMedCrossRefGoogle Scholar
  6. 6.
    Elman L, Dubin R, Kelly M, McCluskey L. Management of oropharyngeal and tracheobronchial secretions in patients with neurologic disease. J Palliat Med. 2005;8:1150–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Bushara KO. Sialorrhea in amyotrophic lateral sclerosis: a hypothesis of a new treatment - botulinum toxin A injections of the parotid glands. Med Hypotheses. 1997;48:337–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Thomas H. Quality assessment tool for quantitative studies. Toronto, ON: Effective Public Health Practice Project; 2003.Google Scholar
  9. 9.
    Deeks JJ, Dinnes J, D’Amico R, Sowden AJ, Sakarovitch C, Song F, Petticrew M, Altman DG. Evaluating non-randomised intervention studies. Health Technol Assess. 2003;7(iii–x):1–173.Google Scholar
  10. 10.
    Contarino M, Pompili M, Tittoto P, Vanacore N, Sabatelli M, Cedrone A, Rapaccini G, Gasbarrini G, Tonali P, Bentivoglio A. Botulinum toxin B ultrasound-guided injections for sialorrhea in amyotrophic lateral sclerosis and Parkinson’s disease. Parkinsonism Relat Disord. 2007;13:299–303.PubMedCrossRefGoogle Scholar
  11. 11.
    Costa J, Rocha M, Ferreira J, Evangelista T, Coelho M, de Carvalho M. Botulinum toxin type-B improves sialorrhea and quality of life in bulbar onset amyotrophic lateral sclerosis. J Neurol. 2008;255:545–50.PubMedCrossRefGoogle Scholar
  12. 12.
    Giess R, Naumann M, Werner E, Riemann R, Beck M, Puls I, Reiners C, Toyka K. Injections of botulinum toxin A into the salivary glands to improve sialorrhoea in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2000;69:121–3.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Rowe D, Erjavec S. An open-label pilot study of intra-parotid botulinum toxin A injections in the treatment of sialorrhoea in motor neurone disease. Milan: The fourteenth International Symposium on ALS/MND; 2003.Google Scholar
  14. 14.
    Scott K, Kothari M, Venkatesh Y, Murphy T, Simmons Z. Parotid gland injections of botulinum toxin A are effective in treating sialorrhea in amyotrophic lateral sclerosis. J Clin Neuromuscul Dis. 2005;7:62–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Gilio F, Iacovelli E, Frasca V, Gabriele M, Giacomelli E, Picchiori F, Soldo P, Cipriani AM, Ruoppolo G, Inghilleri M. Botulinum toxin type A for the treatment of sialorrhoea in amyotrophic lateral sclerosis: a clinical and neurophysiological study. Amyotroph Lateral Scler. 2010;11:359–63.PubMedCrossRefGoogle Scholar
  16. 16.
    Rodriguez-Murphy E, Marti-Bonmati E, Camps-Segui E, Bagan JV. Manually guided botulinum toxin type A submandibular injections for the treatment of sialorrhea in tube-fed patients with advanced amyotrophic lateral sclerosis. Am J Health Syst Pharm. 2011;68:1680–1.PubMedCrossRefGoogle Scholar
  17. 17.
    Neppelberg E, Haugen DF, Thorsen L, Tysnes OB. Radiotherapy reduces sialorrhea in amyotrophic lateral sclerosis. Eur J Neurol. 2007;14:1373–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Weikamp J, Schinagl D, de Swart B, Schelhaas H, Zwarts M. A prospective, randomised controlled study comparing radiotherapy with botulinum toxin A as a treatment for drooling in ALS. Amyotroph Lateral Scler. 2008;9:152.Google Scholar
  19. 19.
    Levitsky G, Alekhin A, Serdyuk A, Skvortsova V. Open-label comparative study of Amitriptyline and Dysport efficacy in control of sialorrhea in ALS. Amyotroph Lateral Scler. 2005;6(Suppl 1):154.Google Scholar
  20. 20.
    Jackson CE, Gronseth G, Rosenfeld J, Barohn RJ, Dubinsky R, Simpson CB, McVey A, Kittrell PP, King R, Herbelin L. Randomized double-blind study of botulinum toxin type B for sialorrhea in ALS patients. Muscle Nerve. 2009;39:137–43.PubMedCrossRefGoogle Scholar
  21. 21.
    Tan EK, Lo YL, Seah A, Auchus AP. Recurrent jaw dislocation after botulinum toxin treatment for sialorrhoea in amyotrophic lateral sclerosis. J Neurol Sci. 2001;190:95–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Meijer J, Van Kuijk A, Geurts A, Schelhaas H, Zwarts M. Acute deterioration of bulbar function after botulinum toxin treatment for sialorrhoea in amyotrophic lateral sclerosis. Am J Phys Med Rehabil. 2008;87:321–4.PubMedCrossRefGoogle Scholar
  23. 23.
    Winterholler M, Erbguth FJ, Wolf S, Kat S, Naumann M, Geiss R, Schwager K, Toyka Kv. Botulinum toxin for the treatment of sialorrhea in ALS: serious side effects of a transductal approach. J Neurol Neurosurg Psychiatry. 2001;70:417–8.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Guidubaldi A, Fasano A, Lalongo T, Piano C, Pompili M, Masciana R, Siciliani L. Botulinum toxin A versus B in sialorrhea: A prospective, randomized, double-blind, crossover pilot study in patients with amyotrophic lateral sclerosis or Parkinson’s disease. Mov Disord. 2011;26:313–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Sterne J, Egger M, Davey Smith G. Investigating and dealing with publication and other biases in meta-analysis. BMJ. 2001;323:101–5.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Stone C, O’Leary N. Systematic review of the effectiveness of botulinum toxin and radiotherapy for sialorrhea in patients with amyotrophic lateral sclerosis. J Pain Symptom Manag. 2009;37:246–58.CrossRefGoogle Scholar
  27. 27.
    Young C, Ellis C, Johnson J, Sathasivam S, Pih N. Treatment for sialorrhea (excessive saliva) in people with motor neuron disease/amyotrophic lateral sclerosis. Cochrane Database Syst Rev. 2011;5:CD006981.PubMedGoogle Scholar
  28. 28.
    Norris SL, Atkins D. Challenges in using nonrandomized studies in systematic reviews of treatment interventions. Ann Intern Med. 2005;142:1112–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Higgins J, Green S. Cochrane Handbook for systematic reviews of interventions, ver. 5.0.2. Oxford: The Cochrane Collaboration; 2009.Google Scholar
  30. 30.
    Swash M. We have a problem: Why have ALS trials been negative? Amyotroph Lateral Scler. 2007;8:259.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Nina Squires
    • 1
    Email author
  • Miles Humberstone
    • 2
  • Adrian Wills
    • 2
  • Antony Arthur
    • 3
  1. 1.Speech and Language Therapy DepartmentNottingham University HospitalNottinghamUK
  2. 2.Division of NeurologyNottingham University HospitalNottinghamUK
  3. 3.School of Nursing Sciences, Faculty of Medicine and Health SciencesUniversity of East AngliaNorwichUK

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