To the Editor:

We thank Drs. Graham, Baker, Boyd, and Flett for their letter in response to our article(1). We appreciate their letter emphasizing that the indication for Botulinum toxin injection is spasticity, not contracture. However, anecdotal evidence suggests that Botulinum toxin is used frequently in conjunction with serial casting for fixed deformities in children with cerebral palsy, and we have personally seen hundreds of children who have had this combination of treatments.

Due to a lack of directly comparable studies, we compared our results to the studies by Drs. Corry (2) and Flett (3), which were the only other reports in the literature examining these two treatments in children with cerebral palsy. It is clearly stated in both the Introduction and Discussion sections of the paper that the Corry and Flett studies “excluded patients with fixed contractures, using serial casting only for spasticity reduction.” We also state that this primary difference between our patient populations (fixed vs. dynamic equinus) may account for the differences in our results.

While we agree that dynamic deformity is a primary indication for Botulinum toxin injection in children with CP, we also recognize that it has other uses in current clinical practice. As Dr. Graham and colleagues acknowledge, our current paper addresses one of these other uses.

1. Kay RM; Rethlefsen SA; Fern-Buneo A; Wren TAL; and Skaggs, DL. Botulinum toxin as an adjunct to serial casting treatment in children with cerebral palsy. J Bone Joint Surg Am, 2004, 86: 2377-84.

2. Corry, I. S.; Cosgrove, A. P.; Duffy, C. M.; McNeill, S.; Taylor, T. C.; and Graham, H. K.: Botulinum toxin A compared with stretching casts in the treatment of spastic equinus: a randomised prospective trial. J Pediatr Orthop, 1998,18(3): 304-11.

3. Flett, P. J.; Stern, L. M.; Waddy, H.; Connell, T. M.; Seeger, J. D.; and Gibson, S. K.: Botulinum toxin A versus fixed cast stretching for dynamic calf tightness in cerebral palsy. J Paediatr Child Health, 1999,35(1): 71-7.

As investigators on a number of previous randomized clinical trials evaluating the use of Botulinum toxin in spasticity associated with cerebral palsy, we read with interest the article by Kay et al, (1). Botulinum toxin A has been widely investigated in a range of animal and clinical studies and certain broad generalizations can be made from the literature:

1. Botulinum neurotoxin A has a high affinity for presynaptic cholinergic nerve terminals and has a predictable dose dependent consistent clinical effect when injected into skeletal muscles affected by spasticity (2,3).

2. The harnessing of this predictable biochemical effect has been established in a wide range of clinical studies such that the evidence for the efficacy of the intervention is greater than for any other medical or surgical procedure currently used in the management of cerebral palsy (4).

3. The principal indication for the clinical use of Botulinum neurotoxin A in children with spasticity associated with cerebral palsy is for the temporary, focal or regional reduction in spasticity to facilitate more normal patterns of motion and on occasions to improve function. In previous work we defined the indication for injection of Botulinum toxin in cerebral palsy to be “dynamic spasticity interfering with function in the absence of fixed contracture” (2,3).

The principal indication for use of Botulinum neurotoxin A in cerebral palsy was and remains reduction of spasticity. However we recognize that many “niche applications” have been explored by other investigators including Kay et al (1,5).

Although we have used Botulinum toxin as an adjunct to serial casting and our anecdotal evidence suggests that it is effective, it is very important to stress that this is not the primary application of this therapy. It was therefore somewhat of a surprise for us to see that Kay et al made a direct comparison between their findings and our studies in which we made a concerted effort to exclude children with fixed contractures. The purpose of the study by Corry et al(6) and Flett et al (7) were clearly to compare two methods of spasticity management for equinus gait not contracture management. In addition, the recommendations for the use of serial casting after Botulinum toxin are to change the casts at weekly intervals and to restrict casting to a period of two weeks in most children or a maximum of three weeks8.

Given that this is the first clinical trial to be published in the Journal of Bone and Joint Surgery addressing the use of Botulinum toxin in cerebral palsy, it is very important for the readers of the journal to understand that the use of Botulinum toxin in the management of dynamic spasticity is supported by a high level of evidence (3,4). The use of Botulinum toxin in this niche application, as an adjunct to serial casting for the management of fixed contractures, is not.

RICHARD BAKER Gait Analysis Service Manager The Hugh Williamson Gait Laboratory The Royal Children’s Hospital Flemington Road Parkville Victoria 3052 Australia E-mail: richard.baker@rch.org.au

ROSLYN BOYD Senior Physiotherapist Department of Orthopaedics The Royal Children’s Hospital Flemington Road Parkville Victoria 3052 Australia E-mail: roslyn.boyd@rch.org.au

PETER J FLETT Director Paediatric Rehabilitation Department of Child and Adolescent Development, Neurology and Rehabilitation Women’s and Children’s Hospital Adelaide South Australia Australia

E-mail: flettp@wch.sa.gov.au

H. KERR GRAHAM Professor of Orthopaedic Surgery Orthopaedic Department The Royal Children’s Hospital Flemington Road Parkville Victoria 3052 Australia

E-mail: kerr.graham@rch.org.au

References

1. Kay RM, Rethlefsen SA, Fern-Buneo A, Wren TAL, Skaggs DL. Botulinum toxin as an adjunct to serial casting treatment in children with cerebral palsy. J Bone Joint Surg Am 2004; 86:2377-84

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

3. Baker R, Jasinski M, Maciag-Tymecka I, Michalowska-Mrozek J, Bonikowski M, Carr L, MacLean J, Lin J-P, Lynch B, Theologis T, Wendorff J, Eunson P, Cosgrove A. Botulinum toxin treatment of spasticity in diplegic cerebral palsy: a randomized, double-blind, placebo-controlled, dose-ranging study. Dev Med Child Neurol 2002;44:666-75

4. Boyd RN, Hays RM. Current evidence for the use of botulinum toxin type A in the management of children with cerebral palsy: a systematic review. Eur J Neurol 2001;8: Supp 5: 1-20

5. Graham HK, Aoki KR, Autti-Ramo I, Boyd RN, Delgado MR, Gaebler- Spira DJ, Gormley ME, Guiyer BM, Heinen F, Holton AF, Matthews D, Molenaers G, Motta F, Garcia Ruiz PJ, Wissel J. Recommendations for the use of botulinum toxin type A in the management of cerebral palsy. Gait and Posture 2000;11:67-79

6. Corry IS, Cosgrove AP, Duffy CM, McNeill S, Taylor TC, Graham HK. Botulinum toxin A compared with stretching casts in the treatment of spastic equinus: a randomised prospective trial. J Pediatr Orthop 1998;18:304-11

7. Flett PJ, Stern LM, Waddy H, Connell TM, Seeger JD, Gibson SK. Botulinum toxin A versus fixed cast stretching for dynamic tightness in cerebral palsy. J Paediatr Child Health 1999;35:71-7

8. Boyd RN, Graham HK. Botulinum toxin A in the management of children with cerebral palsy indications and outcome. Euro J Neurol 1997; 4 (supple 2):15-22