Review by David Weismantel, MD, Michigan State University family practice physician, CPON Co-Investigator.
Randomized double-blind placebo-controlled trial of the effect of botulinum toxin on walking in cerebral palsy. Ubhi T, Bhakta BB, Ives HL, Allgar V, Roussounis SH. Arch Dis Child 2000; 83(6):481-7.
Background
Eighty percent of children of children with cerebral palsy (CP) have some difficulty with walking as a result of lower limb spasticity. Calf muscle spasticity is a particular factor that may interfere with normal walking by preventing an appropriate heel strike. Conventional therapy is based upon physiotherapy, orthoses, and walking aids; however, many children undergo corrective surgical procedures. Systemic antispasticity agents such as baclofen are often effective, yet limited by side effects such as drowsiness and generalized muscle weakness. Intramuscular botulinum toxin (BT-A) may offer targeted antispasticity treatment in children with CP.
Population Studied
Forty children between the ages of 2 and 16 years with either spastic diplegic or hemiplegic cerebral palsy were recruited from 85 consecutive referrals for BT-A therapy to the Yorkshire Regional Child Development Centre in England from 1996 to 1998. Forty-five children were excluded due to fixed contractures, non-ambulatory condition, or an inability to comply with physiotherapy.
Study Design and Validity
Eligible children were randomly assigned to treatment with BT-A (Dysport preparation) or an identical appearing placebo preparation. The BT-A was administered intramuscularly at doses of 25 U/kg (children with diplegic CP) and 15 U/kg (children with hemiplegic CP). The target muscle groups were identified by clinical examination and individualized by the treating clinician.
The overall methodology was good; it included blinding (patients, treating physicians, and clinical investigators) with concealed allocation (within the hospital pharmacy undertaking masking, labeling, and dispensing). It must be noted that the subjects in this study represent a carefully selected group of children with CP, as only 40 of 85 subjects initially considered were later randomly assigned to treatment groups.
Outcomes Measured
Outcome measures included video gait analysis grading initial foot contact, Gross Motor Function Measure, passive ankle dorsiflexion, and physiologic cost index (an index of energy expenditure and proxy for walking efficiency). Measurements were conducted at baseline and at 2, 6, and 12 weeks after injection.
Results
Video gait analysis demonstrated a statistically significant improvement in foot contact at 6 weeks (p=0.02) and 12 weeks (p=0.003) in the BT-A group compared with the placebo group. A statistically significant difference (p=0.04) in the “walking dimension” of the Gross Motor Function Measure also existed. There were no statistically significant differences in passive ankle dorsiflexion or physiologic cost index. Six children in the BT-A treatment group experienced minor side effects, as did one child in the placebo group.
Conclusion
Intramuscular botulinum toxin may be a safe and effective adjunct to conventional physiotherapy and orthoses in the treatment of children with CP and associated gait disturbances.