Assessment of spasticity-related pain in cerebral palsy and the efficacy of its treatment with incobotulinumtoxin A (literature review)

Pain in cerebral palsy (CP) occurs in 30–60% of cases. Pain associated with spasticity (PAS) is one of the most common causes of pain syndrome in cerebral palsy, which is often associated with impairment of the child’s daily life. Recently, more studies have been published on the use of botulinum toxin type A preparations to control PAS.
The review article presents the results of a special pooled analysis of data on the analgesic effect of the drug Xeomin (incobotulinumtoxin A) in the treatment of PAS based on data from three phase III multicentre prospective comparative studies in children and adolescents with spastic forms of cerebral palsy. To evaluate PAS and the effect of incobotulinumtoxin A on it, a special questionnaire (Questionnaire on Pain caused by Spasticity, QPS) was used in these studies. The QPS reflects the child's pain associated with spasticity, which can be observed at rest and during various activities of the child.
It was found that the children included in these studies reported the presence of PAS in more than 80% of cases with lower limb spasticity and in almost 70% of cases with upper limb spasticity. Parents or caregivers of these children observed an even higher prevalence of PAS. The use of incobotulinumtoxin A showed not only a pronounced antispastic effect, but also a significant reduction in the frequency and intensity of PAS in children and adolescents with cerebral palsy during normal daily activities, and during strenuous activities such as physical exercise and rehabilitation treatment. With repeated injection cycles of incobotulinumtoxin A, PAS continued to decrease, ensuring a reduction in pain even when physical activity became more difficult.
Nowadays, injections with incobotulinumtoxin A can be considered as a routine therapeutic approach for the treatment of spasticity and increased muscle tone, but it is certainly an innovative method for effective pain reduction in cerebral palsy patients with lower and upper limb spasticity accompanied by PAS.

1. Bax M, Goldstein M, Rosenbaum P, et al; Executive Committee for the Definition of Cerebral Palsy. Proposed definition and classification of cerebral palsy, April 2005. Dev Med Child Neurol. 2005 Aug;47(8):571-6. doi: 10.1017/s001216220500112x

2. Graham HK, Rosenbaum P, Paneth N, et al. Cerebral palsy. Nat Rev Dis Primers. 2016 Jan 7;2:15082. doi: 10.1038/nrdp.2015.82

3. Ostojic K, Paget SP, Morrow AM. Management of pain in children and adolescents with cerebral palsy: a systematic review. Dev Med Child Neurol. 2019 Mar;61(3):315-21. doi: 10.1111/dmcn.14088. Epub 2018 Oct 31.

4. Badia M, Riquelme I, Orgaz B, et al. Pain, motor function and health-related quality of life in children with cerebral palsy as reported by their physiotherapists. BMC Pediatr. 2014 Jul 27;14:192. doi: 10.1186/1471-2431-14-192

5. McCormick A. Quality of life. In: Panteliadis CP, ed. Cerebral palsy: Multidisciplinary approach. 3rd ed. Cham: Springer; 2018. P.335-42.

6. Mckinnon CT, Meehan EM, Harvey AR, et al. Prevalence and characteristics of pain in children and young adults with cerebral palsy: a systematic review. Dev Med Child Neurol. 2019 Mar;61(3):305-14. doi: 10.1111/dmcn.14111. Epub 2018 Dec 3.

7. Penner M, Xie WY, Binepal N, et al. Characteristics of pain in children and youth with cerebral palsy. Pediatrics. 2013 Aug;132(2):e407-13. doi: 10.1542/peds.2013-0224. Epub 2013 Jul 15.

8. Eriksson E, Hägglund G, Alriksson-Schmidt AI. Pain in children and adolescents with cerebral palsy – a crosssectional register study of 3545 individuals. BMC Neurol. 2020 Jan 11;20(1):15. doi: 10.1186/s12883-019-1597-7

9. Ostergaard CS, Pedersen NSA, Thomasen A, et al. Pain is frequent in children with cerebral palsy and negatively affects physical activity and participation. Acta Paediatr. 2021 Jan;110(1):301-6. doi: 10.1111/apa.15341. Epub 2020 May 26.

10. Sultan T, Wong C. Presence and grade of undertreatment of pain in children with cerebral palsy. Scand J Pain. 2023 Jun 2;23(3):546-52. doi: 10.1515/sjpain-2022-0124

11. Parkinson KN, Dickinson HO, Arnaud C, et al; SPARCLE group. Pain in young people aged 13 to 17 years with cerebral palsy: crosssectional, multicentre European study. Arch Dis Child. 2013 Jun;98(6):434-40. doi: 10.1136/archdischild-2012-303482. Epub 2013 Apr 20.

12. Westbom L, Rimstedt A, Nordmark E. Assessments of pain in children and adolescents with cerebral palsy: a retrospective populationbased registry study. Dev Med Child Neurol. 2017 Aug;59(8):858-63. doi: 10.1111/dmcn.13459. Epub 2017 May 16.

13. Ostojic K, Paget S, Kyriagis M, Morrow A. Acute and Chronic Pain in Children and Adolescents With Cerebral Palsy: Prevalence, Interference, and Management. Arch Phys Med Rehabil. 2020 Feb;101(2):213-9. doi: 10.1016/j.apmr.2019.08.475. Epub 2019 Sep 12.

14. Hareb F, Bertoncelli CM, Rosello O, et al. Botulinum Toxin in Children with Cerebral Palsy: An Update. Neuropediatrics. 2020 Feb;51(1):1-5. doi: 10.1055/s-0039-1694988. Epub 2019 Sep 4.

15. Novak I, Morgan C, Fahey M, 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 Feb 21;20(2):3. doi: 10.1007/s11910-020-1022-z

16. Heinen F, Kanovsky P, Schroeder AS, et al. IncobotulinumtoxinA for the treatment of lower-limb spasticity in children and adolescents with cerebral palsy: A phase 3 study. J Pediatr Rehabil Med. 2021;14(2):183-97. doi: 10.3233/PRM-210040. Erratum in: J Pediatr Rehabil Med. 2022;15(2):407-9.

17. Tilton A, Russman B, Aydin R, et al. AbobotulinumtoxinA (Dysport®) Improves Function According to Goal Attainment in Children With Dynamic Equinus Due to Cerebral Palsy. J Child Neurol. 2017 Apr;32(5):482-7. doi: 10.1177/0883073816686910. Epub 2017 Jan 9.

18. Kanovsky P, Heinen F, Schroeder AS, et al. Safety and efficacy of repeat long-term incobotulinumtoxinA treatment for lower limb or combined upper/lower limb spasticity in children with cerebral palsy. J Pediatr Rehabil Med. 2022;15(1):113-27. doi: 10.3233/PRM210041

19. Roscigno CI. Addressing spasticity-related pain in children with spastic cerebral palsy. J Neurosci Nurs. 2002 Jun;34(3):123-33. doi: 10.1097/01376517-200206000-00005

20. Almina S, Karile Y, Audrone P, Indre B. Analgesic effect of botulinum toxin in children with cerebral palsy: A systematic review. Toxicon. 2021 Aug;199:60-7. doi: 10.1016/j.toxicon.2021.05.012. Epub 2021 Jun 1.

21. Sandahl Michelsen J, Normann G, Wong C. Analgesic Effects of Botulinum Toxin in Children with CP. Toxins (Basel). 2018 Apr 19;10(4):162. doi: 10.3390/toxins10040162

22. Dabrowski E, Chambers HG, Gaebler-Spira D, et al. Incobotulinumtoxin A Efficacy/Safety in Upper-Limb Spasticity in Pediatric Cerebral Palsy: Randomized Controlled Trial. Pediatr Neurol. 2021 Oct;123:10-20. doi: 10.1016/j.pediatrneurol.2021.05.014. Epub 2021 May 21.

23. Geister TL, Quintanar-Solares M, Martin M, et al. Qualitative development of the 'Questionnaire on Pain caused by Spasticity (QPS),' a pediatric patient-reported outcome for spasticity-related pain in cerebral palsy. Qual Life Res. 2014 Apr;23(3):887-96. doi: 10.1007/s11136-013-0526-2. Epub 2013 Sep 24.

24. Geister TL, Bushnell DM, Yang J, et al. Initial psychometric validation of the questionnaire on pain caused by spasticity (QPS). Health Qual Life Outcomes. 2017 Nov 28;15(1):229. doi: 10.1186/s12955-017-0804-8

25. Heinen F, Bonfert M, Kanovsky P, et al. Spasticity-related pain in children/adolescents with cerebral palsy. Part 1: Prevalence and clinical characteristics from a pooled analysis. J Pediatr Rehabil Med. 2022;15(1):129-43. doi: 10.3233/PRM-220011

26. Bonfert M, Heinen F, Kanovsky P, et al. Spasticity-related pain in children/adolescents with cerebral palsy. Part 2: IncobotulinumtoxinA efficacy results from a pooled analysis. J Pediatr Rehabil Med. 2023;16(1):83-98. doi: 10.3233/PRM-220020