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Pediatric Drugs

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01-01-2003 | Therapy In Practice

Spasticity Associated with Cerebral Palsy in Children

Guidelines for the Use of Botulinum A Toxin

Authors: Dr L. Andrew Koman, Beth Paterson Smith, Rajesh Balkrishnan

Published in: Pediatric Drugs | Issue 1/2003

Abstract

Botulinum A toxin produces selective and reversible chemodenervation that can be employed to balance muscle forces across joints in children with cerebral palsy (CP). Currently, there are two commercially available botulinum A toxin formulations (BOTOX® and Dysport®). The amount of botulinum A toxin required depends upon the number of muscles that are targeted, and the size of the patient. In order to achieve adequate chemodenervation with botulinum A toxin, the following conditions must be met: (i) a sufficient number of units of toxin must be injected in order to neutralize neuromuscular junction (NMJ) activity; (ii) an appropriate drug volume is required in order to optimize the delivery of the toxin to the NMJs; and (iii) localization of the injecting needle through the fascia of the target muscle is necessary. Localization of the injection may be facilitated by active electromyography, ultrasonography, palpation of the muscle belly, and/or use of anatomic landmarks.

Botulinum A toxin injections are indicated for use in pediatric patients with CP to: (i) improve motor function by balancing muscle forces across joints; (ii) improve health-related quality of life by decreasing spasticity and/or decreasing caregiver burden; (iii) decrease pain from spasticity; (iv) enhance self-esteem by diminishing inappropriate motor responses; and (v) provide a presurgical diagnostic tool.

Following intramuscular injections of botulinum A toxin, short-term benefits of reduced spasticity are observed in approximately 70–82% of children. The intermediate term (1–2 years) efficacy rate is approximately 50%. The most common deformity treated with toxin injections in pediatric patients with CP is equinus foot deformity. However, efficacy of toxin injections for the management of crouched gait, pelvic flexion contracture, cervical spasticity, seating difficulties, and upper extremity deformity also has been documented. In addition, toxin injections have been shown to manage painful muscle spasticity associated with surgery or application of casts and painful cervical spasticity with or without dystonia. Toxin injections can also be used as a diagnostic tool to determine the appropriateness of other interventions by observing the muscle response to the injection in order to gain additional information for the development of a treatment plan. Botulinum A toxin, when used in appropriate doses, is well tolerated.

Bax M. Terminology and classification of CP. Dev Med Child Neurol 1964; 6: 295–7PubMedCrossRef

Russman BS, Tilton A, Gormley Jr ME. Cerebral palsy: a rational approach to a treatment protocol, and the role of botulinum toxin in treatment. Muscle Nerve Suppl 1997; 6: S181–93PubMedCrossRef

Boyd RN, Graham HK. Botulinum toxin A in the management of children with cerebral palsy: indications and outcome. Eur J Neurol 1997; 4 Suppl. 2: S15–22

Bodine SC, Lieber RL. Peripheral nerve physiology, anatomy, and pathology. In: Buckwalter JA, Einhorn TA, Simon SR, editors. Orthopaedic basic science, biology and biomechanics of the musculoskeletal system. Rosemont (IL): American Academy of Orthopaedic Surgeons, 2000: 628–44

Hagberg B, Hagberg G, Zetterstrom R. Decreasing perinatal mortality: increase in cerebral palsy morbidity. Acta Paediatr Scand 1989; 78: 664–70PubMedCrossRef

Lipkin PH. Epidemiology of the developmental disabilities. In: Capute AJ, Accarado PJ, editors. Developmental disabilities in infancy and childhood. Baltimore (MD): Paul Brookes, 1991: 43–67

Kuban KCK, Leviton A. Cerebral palsy. N Engl J Med 1994; 330: 188–95PubMedCrossRef

Ubhi T. Treatment of paediatric cerebral palsy with Dysport®. Hosp Med 2000; 61: 718–21PubMed

Koman LA, editor. Wake Forest University School of Medicine Orthopaedic Manual. Winston Salem (NC): Orthopaedic Press, 2001

10.

Scott AB, Rosenbaum A, Collins CC. Pharmacologic weakening of extraocular muscles. Invest Ophthalmol 1973; 12: 924–7PubMed

11.

Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology 1980; 87: 1044–9PubMed

12.

Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. J Pediatr Ophthalmol Strabismus 1980; 17: 21–5PubMed

13.

Arthurs B, Flanders M, Codere F, et al. Treatment of blepharospasm with medication, surgery and type A botulinum toxin. Can J Ophthalmol 1987; 22: 24–8PubMed

14.

Biglan AW, May M, Walden PG. Treatment of facial spasm with oculinum (clostridium botulinum toxin): a preliminary report. Am J Otol 1986; 7: 65–70PubMed

15.

Borodic GE, Cozzolino D. Blepharospasm and its treatment, with emphasis on the use of botulinum toxin. Plast Reconstr Surg 1989; 83: 546–54PubMedCrossRef

16.

Koman LA, Mooney III JF, Smith B, et al. Management of cerebral palsy with botulinum-A toxin: preliminary investigation. J Pediatr Orthop 1993; 13: 489–95PubMedCrossRef

17.

Koman LA, Mooney III JF, Smith BP, et al. Botulinum toxin type A neuromuscular blockade in the treatment of lower extremity spasticity in cerebral palsy: a randomized, double-blind, placebo-controlled trial. BOTOX Study Group. J Pediatr Orthop 2000; 20: 108–15PubMed

18.

Aoki KR. Pharmacology and immunology of botulinum toxin serotypes. J Neurol 2001; 248 Suppl. 1: 3–10PubMedCrossRef

19.

Schantz EJ, Johnson EA. Properties and use of botulinum toxin and other microbial neurotoxins in medicine. Microbiol Rev 1992; 56: 80–99PubMed

20.

Dolly JO. Therapeutic and research exploitation of botulinum neurotoxins. Eur J Neurol 1997; 4 Suppl. 2: S5–10

21.

Scales SJ, Chen VA, Yoo BY, et al. SNAREs contribute to the specificity of membrane fusion. Neuron 2000; 26: 457–64PubMedCrossRef

22.

de Paiva A, Meunier FA, Molgo J, et al. Functional repair of motor endplates after botulinum neurotoxin type A poisoning: biphasic switch of synaptic activity between nerve sprouts and their parent terminals. Proc Natl Acad Sci USA 1999; 96: 3200–5PubMedCrossRef

23.

Borodic GE, Ferrante R, Pearce LB, et al. Histologie assessment of dose-related diffusion and muscle fiber response after therapeutic botulinum A toxin injections. Move Disord 1994; 9: 31–9CrossRef

24.

Shaari CM, Sanders I. Quantifying how location and dose of botulinum toxin injections affect muscle paralysis. Muscle Nerve 1993; 16: 964–9PubMedCrossRef

25.

Aquilonius SM, Askmark H, Gillberg PG, et al. Topographical localization of motor endplates in cryosections of whole human muscles. Muscle Nerve 1984; 7: 287–93PubMedCrossRef

26.

Christensen E. Topography of terminal motor innervation in striated muscles from stillborn infants. Am J Phys Med 1959; 38: 65–78PubMedCrossRef

27.

Snobl D, Binaghi LE, Zenker W. Microarchitecture and innervation of the human latissimus dorsi muscle. J Reconstr Microsurg 1998; 14: 171–7PubMedCrossRef

28.

Graham HK, Aoki KR, Autti-Ramo I, et al. Recommendations for the use of botulinum toxin type A in the management of cerebral palsy. Gait Posture 2000; 11: 67–79PubMedCrossRef

29.

Scott AB, Kennedy RA, Stubbs HA. Botulinum A toxin injection as a treatment for blepharospasm. Arch Ophthalmol 1985; 103: 347–50PubMedCrossRef

30.

Dysport®, package insert. Berkshire: Ipsen Ltd, 2000

31.

Molenaers G, Desloovere K, Eyssen M, et al. Botulinum toxin type A treatment of cerebral palsy: an integrated approach. Eur J Neurol 1999; 6 Suppl. 4: S51–7CrossRef

32.

Gormley ME, Gaebler-Spira D, Delgado MR. Use of botulinum toxin type A in pediatric patients with cerebral palsy: a three-center retrospective chart review. J Child Neurol 2001; 16: 113–8PubMed

33.

Bakheit AM, Severa S, Cosgrove A, et al. Safety profile and efficacy of botulinum toxin A (Dysport) in children with muscle spasticity. Dev Med Child Neurol 2001; 43: 234–8PubMedCrossRef

34.

New indication for Dysport. Pharm J 2000; 264: 450

35.

Koman LA, Mooney III JF, Smith BP, et al. Management of spasticity in cerebral palsy with botulinum-A toxin: report of a preliminary, randomized, doubleblind trial. J Pediatr Orthop 1994; 14: 299–303PubMedCrossRef

36.

Molenaers G, Eyssen M, Desloovere K, et al. A multilevel approach to botulinum toxin type A treatment of the (ilio)psoas in spasticity in cerebral palsy. Eur J Neurol 1999; 6 Suppl. 4: S59–62CrossRef

37.

Eames NW, Baker R, Hill N, et al. The effect of botulinum toxin A on gastrocnemius length: magnitude and duration of response. Dev Med Child Neurol 1999; 41: 226–32PubMedCrossRef

38.

Hesse S, Jahnke MT, Luecke D, et al. Short-term electrical stimulation enhances the effectiveness of botulinum toxin in the treatment of lower limb spasticity in hemiparetic patients. Neurosci Lett 1995; 201: 37–40PubMedCrossRef

39.

Ubhi T, Bhakta BB, Ives HL, et al. Randomised, doubleblind, placebo controlled trial of the effect of botulinum toxin on walking in cerebral palsy. Arch Dis Child 2000; 83: 481–7PubMedCrossRef

40.

Childers MK, Stacy M, Cooke DL, et al. Comparison of two injection techniques using botulinum toxin in spastic hemiplegia. Am J Phys Med Rehabil 1996; 75: 462–9PubMedCrossRef

41.

Willenborg MJ, Shilt JS, Smith BP. Technique for iliopsoas ultrasound-guided active electromyography-directed botulinum A toxin injection in cerebral palsy. J Pediatr Orthop 2002; 22: 165–8PubMed

42.

Wissel J, Heinen F, Schenkel A. Botulinum toxin A in the management of spastic gait disorders in children and young adults with cerebral palsy: a randomized, double-blind study of “high dose” versus “low dose” treatment. Neuropediatrics 1999; 30: 120–4PubMedCrossRef

43.

BOTOX®, package insert. Irvine (CA): Allergan Pharmaceuticals, 2000

44.

Borodic G, Johnson E, Goodnough M, et al. Botulinum toxin therapy, immuno-logic resistance, and problems with available materials. Neurology 1996; 46: 26–9PubMedCrossRef

45.

Greene P, Fahn S, Diamond B. Development of resistance to botulinum toxin type A in patients with torticollis. Mov Disord 1994; 9: 213–7PubMedCrossRef

46.

Jankovic J, Schwartz KS. Longitudinal experience with botulinum toxin injections for treatment of blepharospasm and cervical dystonia. Neurology 1993; 43: 834–6PubMedCrossRef

47.

Lu L, Atchabahian A, Mackinnon SE, et al. Nerve injection injury with botulinum toxin. Plast Reconstr Surg 1998; 101: 1875–80PubMedCrossRef

48.

Barwood S, Baillieu C, Boyd R, et al. Analgesic effects of botulinum toxin A: a randomized, placebo-controlled clinical trial. Dev Med Child Neurol 2000; 42: 116–21PubMedCrossRef

49.

Boyd RN, Pliatsios V, Starr R, et al. Biomechanical transformation of the gastrocsoleus muscle with botulinum toxin A in children with cerebral palsy. Dev Med Child Neurol 2000; 42: 32–41PubMedCrossRef

50.

Corry IS, Cosgrove AP, Walsh EG, et al. Botulinum toxin A in the hemiplegic upper limb: a double-blind trial. Dev Med Child Neurol 1997; 39: 185–93PubMedCrossRef

51.

Corry IS, Cosgrove AP, Duffy CM, et al. Botulinum toxin A compared with stretching casts in the treatment of spastic equinus: a randomised prospective trial. J Pediatr Orthop 1998; 18: 304–11PubMed

52.

Cosgrove AP, Corry IS, Graham HK. Botulinum toxin in the management of the lower limb in cerebral palsy. Dev Med Child Neurol 1994; 36: 386–96PubMedCrossRef

53.

Fehlings D, Rang M, Glazier J, et al. An evaluation of botulinum-A toxin injections to improve upper extremity function in children with hemiplegic cerebral palsy. J Pediatr 2000; 137: 331–7PubMedCrossRef

54.

Flett PJ, Stern LM, Waddy H, et al. Botulinum toxin A versus fixed cast stretching for dynamic calf tightness in cerebral palsy. J Paediatr Child Health 1999; 35: 71–7PubMedCrossRef

55.

Friedman A, Diamond M, Johnston MV, et al. Effects of botulinum toxin A on upper limb spasticity in children with cerebral palsy. Am J Phys Med Rehabil 2000; 79: 53–9PubMedCrossRef

56.

Garcia Ruiz PJ, Pascual PI, Sanchez BV. Progressive response to botulinum A toxin in cerebral palsy. Eur J Neurol 2000; 7: 191–3PubMedCrossRef

57.

Gooch JL, Sandell TV. Botulinum toxin for spasticity and athetosis in children with cerebral palsy. Arch Phys Med Rehabil 1996; 77: 508–51PubMedCrossRef

58.

Koman LA, Smith BP, Tingey CT, et al. The effect of botulinum toxin type A injections on the natural history of equinus foot deformity in pediatric cerebral palsy patients. Eur J Neurol 1999; 6 Suppl. 4: S19–22CrossRef

59.

Koman LA, Brashear A, Rosenfeld S, et al. Botulinum toxin type A neuromuscular blockade in the treatment of equinus foot deformity in cerebral palsy: a multicenter, open-label clinical trial. Pediatrics 2001; 108: 1062–71PubMedCrossRef

60.

Suputtitada A. Managing spasticity in pediatric cerebral palsy using a very low dose of botulinum toxin type A: preliminary report. Am J Phys Med Rehabil 2000; 79: 320–6PubMedCrossRef

61.

Sutherland DH, Kaufman KR, Wyatt MP, et al. Effects of botulinum toxin on gait of patients with cerebral palsy: preliminary results. Dev Med Child Neurol 1994; 36: 11–2

62.

Sutherland DH, Kaufman KR, Wyatt MP, et al. Injection of botulinum A toxin into the gastrocnemius muscle of patients with cerebral palsy: a 3-D motion analysis study. Dev Med Child Neurol 1995; 37: 17–8

63.

Sutherland DH, Kaufman KR, Wyatt MP, et al. Double-blind study of botulinum A toxin injections into the gastrocnemius muscle in patients with cerebral palsy. Gait Posture 1999; 10: 1–9PubMedCrossRef

64.

Thompson NS, Baker RJ, Cosgrove AP, et al. Musculoskeletal modelling in determining the effect of botulinum toxin on the hamstrings of patients with crouch gait. Dev Med Child Neurol 1998; 40: 622–5PubMedCrossRef

65.

Wall SA, Chait LA, Temlett JA, et al. Botulinum A hemodenervation: a new modality in cerebral palsied hands. Br J Plast Surg 1993; 46: 703–6PubMedCrossRef

66.

Wissel J, Muller J, Baldauf A, et al. Gait analysis to assess the effects of botulinum toxin type A treatment in cerebral palsy: an open-label study in 10 children with equinus gait pattern. Eur J Neurol 1999; 6 Suppl. 4: S63–7CrossRef

67.

Wong V. Use of botulinum toxin injection in 17 children with spastic cerebral palsy. Pediatr Neurol 1998; 18: 124–31PubMedCrossRef

68.

Yang TF, Chan RC, Chuang TY, et al. Treatment of cerebral palsy with botulinum toxin: evaluation with gross motor function measure. J Formos Med Assoc 1999; 98: 832–6PubMed

69.

Zelnik N, Giladi N, Goikhman I, et al. The role of botulinum toxin in the treatment of lower limb spasticity in children with cerebral palsy: a pilot study. Isr J Med Sci 1997; 33: 129–33PubMed

70.

Van Heest AE. Applications of botulinum toxin in orthopedics and upper extremity surgery. Tech Hand Upper Extrem Surg 1997; 1: 27–34CrossRef

71.

Kirschner J, Berweck S, Mall V, et al. Botulinum toxin treatment in cerebral palsy: evidence for a new treatment option. J Neurol 2000; 248 Suppl. 1: 28–30

72.

Heinen F, Linder M, Mall V, et al. Adductor spasticity in children with cerebral palsy and treatment with botulinum toxin type A: the parents’ view of functional outcome. Eur J Neurol 1999; 6 Suppl. 4: S47–50CrossRef

73.

Msall ME, DiGaudio K, Rogers BT. The functional independence measure for children (WeeFIM). Clin Pediatr 1994; 33: 421–30CrossRef

Title: Spasticity Associated with Cerebral Palsy in Children
Guidelines for the Use of Botulinum A Toxin
Authors: Dr L. Andrew Koman
Beth Paterson Smith
Rajesh Balkrishnan
Publication date: 01-01-2003
Publisher: Springer International Publishing
Published in: Pediatric Drugs / Issue 1/2003
Print ISSN: 1174-5878
Electronic ISSN: 1179-2019
DOI: https://doi.org/10.2165/00128072-200305010-00002

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Spasticity Associated with Cerebral Palsy in Children

Guidelines for the Use of Botulinum A Toxin

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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