‘Botulinum toxin A injection for children with spastic cerebral palsy’

cerebral palsy’ SIR–Cerebral palsy (CP) is a group of persistent motor disorders or postural disturbances secondary to non-progressive damage in the developing brain. In China, the prevalence rate of CP from 1997 to 1998 was 1.92% among 1to 6-year-old children, with spastic CP accounting for 60 to 70%. It is difficult to decrease muscle spasticity in children with spastic CP. Many methods have been used such as nerve blockers and muscular relaxants, etc. Botulinum toxin type A (BoNT-A) is a biological toxin which can prevent acetylcholine releasing into the presynaptic cleft of the neuromuscular junction. BoNT-A has been used to decrease muscle spasticity in some parts of the world in recent years. Our research aimed to validate the efficacy and safety of BoNT-A for children with spastic CP. Sixty-five in-patients (47 males, 18 females; mean age 5.2y [SD 1.7y], range 2–10y) took part in the study. They were all admitted to hospital for BoNT-A treatment in our pediatric department, coming from almost every province of China (except for Xinjiang province), and they were randomly selected from May 2001 to Jan 2006. Thirty-five children had diplegic CP, four hemiplegic, 15 quadriplegic, four monoplegic, and seven paraplegic. Six children were Gross Motor Function Classification System (GMFCS) Level I, 15 were Level II, 28 were Level III, 13 were Level IV, and three were Level V. Children with acute infectious diseases, disorder of neuromuscular transmission, serious cardiopathy, serious liver dysfunction, or bleeding and coagulation disorder, were excluded. Children with modified Ashworth Scale (MAS) ‡2 were included in the study. The BoNT-A was manufactured by LanZhou Vaccine and Serum Institute of China. The dose was 3unit ⁄ kg for small muscles, 4 or 5unit ⁄ kg for large muscles, and a maximal dose was 200 units. Gastrocnemius, soleus, tibialis posterior, biceps femoris, and adductor were target muscles for injection. The injection was guided by B-ultrasound in five patients. The degree of muscle spasticity was measured according to MAS. Gait and range of movement were evaluated with the Physician Rating Scale (PRS). The range of motion was assessed at hip joint, knee joint, and ankle joint. Muscle tone and gait were assessed at entry, 1 month, and 3 months after the injection. The study was approved by the ethics committee of Tiantan hospital, and informed consent was obtained for publication of the results. The therapeutic effect usually occurred within 1 to 3 days after injection: three children within 24 hours, 11 children from 1 to 2 days, 44 children from 2 to 3 days, and only seven children from 3 to 7 days. There was significant improvement in muscle tone and gait, as shown in Table I. The average duration of effect was 3 to 6 months. Adverse events often started within 1 week and lasted no more than 2 weeks. There was no severe or systemic reaction. Local reactions included pain (six patients), ecchymosis (five patients), adjacent muscle weakness (three patients), and transient unsteady gait (two patients). No allergy occurred. The effect often started within 1 to 3 days in small muscles and within 3 to 5 days in large muscles. The range of joint motion (hip, knee, and ankle) was improved most significantly after BoNT-A injection, probably due to the superficial location of involved muscles. Spastic equinus was not apparently improved, possibly because the peroneal muscle and the tibialis posterior were difficult to inject accurately without guiding. Walking ability varied strongly with spastic CP type and was correlated with intellectual impairment and sensory disturbance, as well as the coordination of agonist-antagonist muscles. In our study, gait velocity as assessed by PRS was improved slightly in children whose GMFCS level was more than III (p<0.001). The tone of involved muscles was reduced after BoNT-A injection (p<0.001) and this perhaps altered the balance of agonist-antagonist muscle action. The effect duration of our study was 3 to 6 months. Longterm analysis of the physiology has shown that the motor end plates continue to release acetylcholine about 3 months after BoNT-A injection. The side effects of BoNT-A were local, self-limited, and mild in our trial. Local side effects included pain, ecchymosis, focal weakness, etc. Local pain occurred most frequently due to soft tissue injury and the large volume of solution. Ecchymosis was another common side effect. Some patients showed unstable gait, which lasted no more than 1 week. Employing electromyography and B-ultrasound to define the optimal target muscles was an effective method to decrease the incidence of side effects. In conclusion, the study suggests that BoNT-A is safe and effective for children with spastic CP. Together with other adjuvant treatments, BoNT-A injections might be more effective in improving the quality of life in children with spastic CP.