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Two-year placebo-controlled trial of botulinum toxin A for leg spasticity in cerebral palsy

From The Walton Centre for Neurology and Neurosurgery (A.P.M.), Liverpool; Liverpool Alder Hey Children’s Hospital (R.A.A.-H., L.R., H.P.J.W., K.M.); and Centre for Medical Statistics and Health Evaluation (C.T.S., P.R.W.), School of Health Sciences, University of Liverpool, UK.

Address correspondence and reprint requests to Dr Moore, The Walton Centre for Neurology and Neurosurgery, Lower Lane, Liverpool L9 7LJ, UK peter.moore{at}thewaltoncentre.nhs.uk

Background: The controlled evidence favoring botulinum toxin A (BtA) treatment for spasticity in cerebral palsy is based on short-term studies.

Methods: We conducted a randomized, double-blind, placebo-controlled, parallel-group study of BtA (Dysport) for leg spasticity in 64 children with cerebral palsy. For 2 years, the children received trial injections of up to 30 mu/kg every 3 months if clinically indicated.

Results: For the primary endpoints of Gross Motor Function Measure (GMFM) and Pediatric Evaluation of Disability Index (PEDI) scaled scores at 2 years (trough rather than peak effect), there were no differences between the mean change scores of each group. For the GMFM total score, the 95% CI of –4.81 to 1.90 excluded a 5-point difference in either direction, and a 2-point benefit with 95% confidence. There were no differences in adverse events.

Conclusions: There was no evidence of cumulative or persisting benefit from repeated botulinum toxin A (BtA) at the injection cycle troughs at 1 year or 2 years. The dose was not enough to change spasticity measures and thus GMFM in this heterogeneous group. Ceiling effects in GMFM and Pediatric Evaluation of Disability Index (PEDI) may have reduced responsiveness. This finding does not deny the value, individually, of single injection cycles or prove that repeating them is unhelpful. In this regard, BtA treatment can be viewed in the same light as other temporary measures to relieve spasticity, such as oral or intrathecal agents: there is no evidence of continuing benefit if the treatment ceases. The study provides long-term, fully controlled adverse event data and has not revealed any long-term adverse effects.

Abbreviations: BtA = botulinum toxin A; CP = cerebral palsy; GMFM = Gross Motor Function Measure; GMFCS = Gross Motor Function Classification System; mu = mouse units; PEDI = Pediatric Evaluation of Disability Index.

Supplemental data at www.neurology.org

The charity Action Medical Research funded this study (grant AP0622).

Disclosures: A.P.M. has received payment from Ipsen UK and other companies promoting botulinum toxins for advice and for educational help. His unit has received funds from them to support other research with botulinum toxins. The remaining authors report no disclosures.

Received September 23, 2005. Accepted in final form March 17, 2008.