Purpose The purpose of this review is to clarify the role of botulinum toxin serotype A (BTX-A) in the treatment of children with cerebral palsy (CP), with a special focus on the lower limb. Background The treatment of spasticity is central in the clinical management of children with CP. BTX-A blocks the release of acetylcholine at the motor end plate, causing a temporary muscular denervation and, in an indirect way, a reduced spasticity. Children with increased tone develop secondary problems over time, such as muscle contractures and bony deformities, which impair their function and which need orthopaedic surgery. However in these younger children, delaying surgery is crucial because the results of early surgical interventions are less predictable and have a higher risk of failure and relapse. As BTX-A treatment reduces tone in a selective way, it allows a better motor control and muscle balance across joints, resulting in an improved range of motion and potential to strengthen antagonist muscles, when started at a young age. The effects are even more obvious when the correct BTX-A application is combined with other conservative therapies, such as physiotherapy, orthotic management and casts. There is now clear evidence that the consequences of persistent increased muscle tone can be limited by applying an integrated multi-level BTX-A treatment approach. Nevertheless, important challenges such as patient selection, defining appropriate individual goals, timing, dosing and dilution, accuracy of injection technique and how to measure outcomes will be questioned. Therefore, ''reflection is more important than injection'' remains an actual statement.

The integrated multilevel BTX-A approach is successful in children with CP. Several factors might help the clinician to select patients that are most likely to benefit from the treatment, to assure the most optimal treatment strategy and to predict the outcome. Each treatment should be carefully planned and goals should be well chosen, because the effectiveness of the BTX-A treatment may decrease with increasing number of treatments in the same patient.

At the University Hospital of Pellenberg (Belgium), more than 1000 patients have been treated with Botulinum toxin type A (BTX-A) over the last decade. Ten percent of these patients (n=106) received multiple (at least four times), multi-level, high-dosage treatments. The aim of this study was to evaluate the stability of dosage and treatment intervals in long-term, multi-level, high-dosage treated children with cerebral palsy and to evaluate the evidence for a safe and stable response to this treatment. Data on disease, age, dosage and target muscles were extracted for each treatment session of 106 patients who received multiple BTX-A treatment sessions. Patients had a follow-up of 4y 6mo (range 1y 8mo-8y 9mo) on average and received 4 to 12 BTX-A treatments within the period of January 1996 and December 2005. Patients received a mean dosage of 23.5+/-5.2U/kgbw at first treatment with stable subsequent values. Mean dosages for children with diplegia, hemiplegia and quadriplegia were 24.5+/-4.7U/kgbw, 15.9+/-3.7U/kgbw and 22.0+/-4.8U/kgbw, respectively. Mean age at first treatment was 4y 6mo (range 1y 11mo-18y 10mo) with a majority of patients (76.4%) first treated within 2 and 4y of age. Treatment intervals of approximately 1y remained stable within four, five and six subsequent treatments. Long-term, high-dosage, multi-level BTX-A applications can be considered as a safe and stable treatment option for children with cerebral palsy and the formation of antibodies, responsible for secondary non-response, can be indirectly precluded.