Treatment of sialorrhea in adults and children using botulinum toxin type A

Sialorrhea is a common condition in various diseases that occur in neurological practice among adult patients and children. Excessive accumulation of saliva in the oral cavity and its release outside the oral cavity is a complex medical problem that often leads to complications of the underlying disease and requires independent treatment. Severe drooling leads to conditions that significantly limit the patient’s socialization, complicates his care, and places an additional economic burden on the patient’s family members. The range of treatment strategies aimed at reducing or eliminating sialorrhea is very wide and includes cognitive behavioral therapy, medication, botulinum toxin injections, and surgery. The choice of an available treatment option for sialorrhea is based on the severity of the underlying disease and the results of assessing the severity of saliva accumulation in the oral cavity. Drug therapy, as well as surgical treatments, are often accompanied by adverse events. A modern and safe method of treatment, with the fewest side effects, is the injection of botulinum toxin type A into the parotid and submandibular salivary glands. The absence of difficulties in using this treatment method allows it being recommended in routine medical practice by a neurologist trained in the administration of botulinum toxins. The article presents a review of the world literature over the past twenty years, as well as a standard scheme for the use of botulinum toxin type A (incobotulinumtoxinA) for the treatment of sialorrhea in adults and children, with justification for the use of the drug under mandatory ultrasound control and certain diseases under anesthesia.

Contribution:
Ivolgin A.F. — concept and design of the review, writing the text, editing;
Avseitseva T.Y. — writing the text;
Kurenkov A.L. — concept and design of the review, writing the text, editing;
Artemenko A.R. — writing the text, editing;
Mazur A.S. — writing the text, editing;
All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: August 23, 2023
Accepted: September 30, 2023
Published: December 28, 2023

1. Lakraj A.A., Moghimi N., Jabbari B. Sialorrhea: anatomy, pathophysiology and treatment with emphasis on the role of botulinum toxins. Toxins (Basel). 2013; 5(5): 1010–31. https://doi.org/10.3390/toxins5051010

2. Andersen P.M., Abrahams S., Borasio G.D., de Carvalho M., Chio A., Van Damme P., et al. EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS) – revised report of an EFNS task force. Eur. J. Neurol. 2012; 19(3): 360–75. https://doi.org/10.1111/j.1468-1331.2011.03501.x

3. Ruiz-Roca J.A., Pons-Fuster E., Lopez-Jornet P.J. Effectiveness of the botulinum toxin for treating sialorrhea in patients with Parkinson’s disease: a systematic review. Clin. Med. 2019; 8(3): 317. https://doi.org/10.3390/jcm8030317

4. Squires N., Wills A., Rowson J. The management of drooling in adults with neurological conditions. Curr. Opin. Otolaryngol. Head Neck Surg. 2012; 20(3): 171–6. https://doi.org/10.1097/moo.0b013e32835328ec

5. Zalyalova Z.A. Salivation after stroke. Zhurnal nevrologii i psikhiatrii im. C.C. Korsakova. 2017; 117(1): 85–9. https://doi.org/10.17116/jnevro20171171185-89 https://elibrary.ru/xxdsrz (in Russian)

6. Malek N., Lawton M.A., Grosset K.A., Bajaj N., Barker R.A., Burn D.J., et al. Autonomic dysfunction in early Parkinson’s disease: results from the United Kingdom tracking Parkinson’s study. Mov. Disord. Clin. Pract. 2016; 4(4): 509–16. https://doi.org/10.1002/mdc3.12454

7. Martinez-Martin P., Rodriguez-Blazquez C., Kurtis M.M., Chaudhuri K.R. The impact of non-motor symptoms on health-related quality of life of patients with Parkinson’s disease. Mov. Disord. 2011; 26(3): 399–406. https://doi.org/10.1002/mds.23462

8. Koshkarev M.A., Ivolgin A.F., Litvinenko I.V., Dyskin D.E. Possibilities of treatment of severe motor disorders with the first established diagnosis of Parkinson’s disease. Gospital’naya meditsina: nauka i praktika. 2020; 1(1): 17–23. https://elibrary.ru/oqefua (in Russian)

9. Vandenberghe N., Vallet A.E., Petitjean T., Le Cam P., Peysson S., Guérin C., et al. Absence of airway secretion accumulation predicts tolerance of noninvasive ventilation in subjects with amyotrophic lateral sclerosis. Respir. Care. 2013; 58(9): 1424–32. https://doi.org/10.4187/respcare.02103

10. Kang Y., Chun M.H., Lee S.J. Evaluation of salivary aspiration in brain-injured patients with tracheostomy. Ann. Rehabil. Med. 2013; 37(1): 96–102. https://doi.org/10.5535/arm.2013.37.1.96

11. Fairhurst C.B., Cockerill H. Management of drooling in children. Arch. Dis. Child. Educ. Pract. Ed. 2011; 96(1): 25–30. https://doi.org/10.1136/adc.2007.129478

12. Walshe M., Smith M., Pennington L. Interventions for drooling in children with cerebral palsy. Cochrane Database Syst. Rev. 2012; 11: CD008624. https://doi.org/10.1002/14651858.CD008624.pub3

13. Speyer R., Cordier R., Kim J.H., Cocks N., Michou E., Wilkes-Gillan S. Prevalence of drooling, swallowing, and feeding problems in cerebral palsy across the lifespan: a systematic review and meta-analyses. Dev. Med. Child. Neurol. 2019; 61(11): 1249–58. https://doi.org/10.1111/dmcn.14316

14. McIntyre S., Goldsmith S., Webb A., Ehlinger V., Hollung S.J., McConnell K., et al. Global prevalence of cerebral palsy: A systematic analysis. Dev. Med. Child. Neurol. 2022; 64(12): 1494–506. https://doi.org/10.1111/dmcn.15346

15. Rosenthal M. Life expectancy and its adjustment in cerebral palsy with severe impairment: Are we doing this right? Dev. Med. Child Neurol. 2022; 64(6): 709–14. https://doi.org/10.1111/dmcn.15120

16. Parkes J., Hill N., Platt M.J., Donnelly C. Oromotor dysfunction and communication impairments in children with cerebral palsy: a register study. Dev. Med. Child Neurol. 2010; 52(12): 1113–9. https://doi.org/10.1111/j.1469-8749.2010.03765.x

17. Wright R.E., Wright F.R., Carson C.A. Videofluoroscopic assessment in children with severe cerebral palsy presenting with dysphagia. Pediatr. Radiol. 1996; 26(10): 720–2. https://doi.org/10.1007/BF01383388

18. Sforza E., Onesimo R., Leoni C., Giorgio V., Proli F., Notaro F., et al. Drooling outcome measures in paediatric disability: a systematic review. Eur. J. Pediatr. 2022; 181(7): 2575–92. https://doi.org/10.1007/s00431-022-04460-5

19. Nascimento D., Carmona J., Mestre T., Ferreira J.J., Guimarães I. Drooling rating scales in Parkinson’s disease: A systematic review. Parkinsonism Relat. Disord. 2021; 91: 173–80. https://doi.org/10.1016/j.parkreldis.2021.09.012

20. Klochkova O.A., Kurenkov A.L., Karimova Kh.M., Bursagova B.I., Namazova-Baranova L.S., Kuzenkova L.M., et al. Drooling in patients with cerebral palsy: the effectiveness of botulinum toxin a treatment. Pediatricheskaya farmakologiya. 2015; 12(4): 398–406. https://doi.org/10.15690/pf.v12i4.1420 https://elibrary.ru/umtznz (in Russian)

21. Kurenkov A.L., Kuzenkova L.M., Chernikov V.V., Bursagova B.I., Nezhel’skaya A.A., Artemenko A.R. IncobotulinumtoxinA in the treatment of sialorrhea in patients with infantile cerebral palsy. Nevrologiya, neyropsikhiatriya, psikhosomatika. 2021; 13(4): 52–9. https://doi.org/10.14412/2074-2711-2021-4-52-59 https://elibrary.ru/xdxbts (in Russian)

22. Isaacson J., Patel S., Torres-Yaghi Y., Pagán F. Sialorrhea in Parkinson’s disease. Toxins (Basel). 2020; 12(11): 691. https://doi.org/10.3390/toxins12110691

23. Novak I., Morgan C., Fahey M., Finch-Edmondson M., Galea C., Hines A., et al. State of the evidence traffic lights 2019: Systematic review of interventions for preventing and treating children with cerebral palsy. Curr. Neurol. Neurosci. Rep. 2020; 20(2): 3. https://doi.org/10.1007/s11910-020-1022-z

24. McGeachan A.J., Hobson E.V., Al-Chalabi A., Stephenson J., Chandran S., Crawley F., et al. A multicentre evaluation of oropharyngeal secretion management practices in amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Frontotemporal Degener. 2017; 18(1-2): 1–9. https://doi.org/10.1080/21678421.2016.1221433

25. Restivo D.A., Panebianco M., Casabona A., Lanza S., Marchese-Ragona R., Patti F., et al. Botulinum toxin A for sialorrhoea associated with neurological disorders: evaluation of the relationship between effect of treatment and the number of glands treated. Toxins (Basel). 2018; 10(2): 55. https://doi.org/10.3390/toxins10020055

26. Banfi P., Ticozzi N., Lax A., Guidugli G.A., Nicolini A., Silani V. A review of options for treating sialorrhea in amyotrophic lateral sclerosis. Respir. Care. 2015; 60(3): 446–54. https://doi.org/10.4187/respcare.02856

27. Pellegrini A., Lunetta C., Ferrarese C., Tremolizzo L. Sialorrhoea: how to manage a frequent complication of motor neuron disease. EMJ Neurol. 2015; 3(1): 107–13. https://doi.org/10.33590/emjneurol/10312710

28. Lagalla G., Millevolte M., Capecci M., Provinciali L., Ceravolo M.G. Long-lasting benefits of botulinum toxin type B in Parkinson’s disease-related drooling. J. Neurol. 2009; 256(4): 563–7. https://doi.org/10.1007/s00415-009-0085-1

29. Jost W.H., Friedman A., Michel O., Oehlwein C., Slawek J., Bogucki A., et al. SIAXI: Placebo-controlled, randomized, double-blind study of incobotulinumtoxinA for sialorrhea. Neurology. 2019; 92(17): e1982–91. https://doi.org/10.1212/WNL.0000000000007368

30. Berweck S., Bonikowski M., Kim H., Althaus M., Flatau-Baqué B., Mueller D., et al. Placebo-controlled clinical trial of incobotulinumtoxinA for sialorrhea in children: SIPEXI. Neurology. 2021; 97(14): e1425–36. https://doi.org/10.1212/WNL.0000000000012573

31. Jost W.H., Steffen A., Berweck S. A critical review of incobotulinumtoxinA in the treatment of chronic sialorrhea in pediatric patients. Expert. Rev. Neurother. 2021; 21(10): 1059–68. https://doi.org/10.1080/14737175.2021.1979959

32. Abboud W.A., Nadel S., Hassin-Baer S., Arad A., Dobriyan A., Yahalom R. Ultrasound-guided botulinum toxin injections into the salivary glands for the treatment of drooling. Isr. Med. Assoc. J. 2019; 21(2): 116–9.

33. Jost W.H. The option of sonographic guidance in Botulinum toxin injection for drooling in Parkinson’s disease. J. Neural. Transm. (Vienna). 2016; 123(1): 51–5. https://doi.org/10.1007/s00702-015-1416-2

34. Dogu O., Apaydin D., Sevim S., Talas D.U., Aral M. Ultrasound-guided versus ‘blind’ intraparotid injections of botulinum toxin-A for the treatment of sialorrhoea in patients with Parkinson’s disease. Clin. Neurol. Neurosurg. 2004; 106(2): 93–6. https://doi.org/10.1016/j.clineuro.2003.10.012

35. Breheret R., Bizon A., Jeufroy C., Laccourreye L. Ultrasound-guided botulinum toxin injections for treatment of drooling. Eur. Ann. Otorhinolaryngol. Head Neck Dis. 2011; 128(5): 224–9. https://doi.org/10.1016/j.anorl.2010.12.010