Children with spastic cerebral palsy : aspects of muscle activity and botulinum toxin a treatment

Backgound: Cerebral Palsy (CP) is a heterogeneous disorder in which movement and posture are always affected. Spasticity is one of the most common symptoms. A spastic muscle prevents normal motor behaviour and is believed to cause secondary contractures. Other motor symptoms include central dyscoordination causing defects in coordination and excecution of motion and excessive co-contraction in antagonist muscles. Muscle activity in antagonist and adjacent muscles during voluntary movements such as maximum voluntary isometric contraction (MVIC) is not completely understood in children with CP nor in children with typical development (TD). Despite a lack of strong evidence from randomised controlled trials and little long-term data, intramuscular injections with botulinum toxin A (BoNT-A) for treatment of increased muscle tone in children with CP has become increasingly popular over the last decade.

Aims: The aims of the thesis were to compare the patterns of muscle activation during MVIC in lower extremity muscles and determine whether children with CP have more co-activity than TD children. A further aim was to write a comprehensive review on BoNT-A treatment with recommendations for future research. Further aims were to evaluate the effect of early BoNT-A treatment in toddlers with CP, and to prospectively evaluate any long-term effects of BoNT-A on muscle tone and joint range of motion (ROM) in the lower extremities of children with CP.

Methods/Results: Children with diplegic and hemiplegic CP and TD were assessed with surface EMGs. It was found that children with CP display greater variability in muscle onset order, shorter latencies to onset of other muscles than the intended muscle and twice as much co-activity in both antagonist and adjacent muscles, during MVIC compared to TD children. Ninety-four children with CP were prospectively followed for a maximum of 3 years and 7 months during which time they received a maximum of eight injections per muscle of BoNT-A. Outcome measurements included muscle tone and joint range of motion (ROM). BoNT-A injections reduced long-term spasticity in all muscle-groups examined: the gastrocnemius, hamstring, and adductor muscles. Improvement in ROM, however, was only significant after the first injection; after further injections, joint ROM was reduced. Children with CP, under 2 years of age at study start, participated in a randomized trial which compared the effects of one year of early BoNT-A treatment in the gastrocnemius muscle combined with a daily stretching program to a stretching program alone. The effects on ankle and knee ROM, muscle tone in ankle and knee flexors, gross motor function measure (GMFM) and pediatric evaluation of disability inventory (PEDI) were evaluated at one year and at 3.5 years after study commencement. Gait was evaluated with 3D-gait analysis at 5 years of age. Early treatment with BoNT-A significantly increased knee joint ROM and although not significantly, also increased ankle joint dorsiflexion in the BoNT-A group after 1 year. Children in the control group experienced significantly reduced joint ROM at both joint levels at 3.5 years after study commencement. No differences in GMFM or PEDI scores or 3D-gait data were detected comparing the groups.

Conclusions: The activation of muscles differs between children with CP and children with TD when performing a voluntary movement and children with CP express twice as much co-activity. Early BoNT-A intervention in toddlers with CP seems to influence muscle tone and contracture development also after 3.5 years. The effect on gait development remain inconclusive.When BoNT-A treatment in older children (mean age 5.5y at treatment start) is evaluated this suggests that BoNT-A can be effective in reducing muscle tone over a longer period, but not in preventing development of contractures in spastic muscles. The dissociation between the effects on muscle tone and ROM indicates that development of contractures is not coupled to increased muscle tone alone, but might be caused by other mechanisms.

List of scientific papers

I. Tedroff K, Knutson LM, Soderberg GL (2006). "Synergistic muscle activation during maximum voluntary contractions in children with and without spastic cerebral palsy." Dev Med Child Neurol 48(10): 789-96
https://pubmed.ncbi.nlm.nih.gov/16978457

II. Tedroff K, Knutson LM, Soderberg GL (2008). "Co-activity during maximum voluntary contraction: a study of four lower-extremity muscles in children with and without cerebral palsy." Dev Med Child Neurol 50(5): 377-81. Epub 2008 Mar 24
https://pubmed.ncbi.nlm.nih.gov/18371092

III. Forssberg H, Tedroff KB (1997). "Botulinum toxin treatment in cerebral palsy: intervention with poor evaluation?" Dev Med Child Neurol
https://pubmed.ncbi.nlm.nih.gov/9344058

IV. Tedroff K, Granath F, Forssberg H, Haglund-Åkerlind Y (2009). "Long-term effects of botulinum toxin A in children with cerebral palsy." Developmental Medicine & Child Neurology 51(2): 120-7
https://pubmed.ncbi.nlm.nih.gov/19191845

V. Tedroff K, Löwing K, Gutierrez-Farewik EM, Haglund-Åkerlind Y, Forssberg H (2009). "Botulinum toxin A treatment in toddlers with cerebral palsy: Effects on muscle tone, contracture development and gait pattern. A randomized controlled trial." (Manuscript)
https://doi.org/10.1111/j.1651-2227.2010.01767.x