Botulinum toxin-A with and without rehabilitation for the treatment of spastic cerebral palsy

Abstract

Objective

To determine the efficacy of botulinum toxin-A (BTX-A) nerve block, with and without rehabilitation, in the treatment of spastic cerebral palsy.

Methods

Patients (aged 1–23 years) with spastic cerebral palsy underwent nerve block with BTX-A, followed by ≥ 2 h/day rehabilitation (experimental group) or <2 h/day rehabilitation (control group). Muscle tension and motor function were evaluated pre-block using the Modified Ashworth Scale (MAS) and gross motor function measure (GMFM), respectively. MAS was assessed weekly to determine duration of action of BTX-A; GMFM was assessed at 1 year post-block.

Results

There were no significant differences between the experimental group (n = 120) and the control group (n = 124) in age, body weight, pre-block MAS or GMFM, or BTX-A duration of action. MAS was significantly improved in both groups at 1 month post-block. At 1 year post-block, GMFM was significantly improved in both groups, with a significantly greater improvement seen in the experimental group compared with the control group.

Conclusion

BTX-A block improved muscle tension and motor function. Rehabilitation training, following the block, resulted in greater improvements to motor function than block alone.

Introduction

The birth prevalence of cerebral palsy is 2–5%,^1,2 with spastic cerebral palsy accounting for 60–70% of cases.^3,4 Muscle spasms impede normal motor development and also result in contractures, deformity, pain and other complications,^5–7 therefore relief from spasticity is a major focus of cerebral palsy treatment.

Treatments for spasticity include rehabilitation, oral administration of muscle relaxants, nerve block, baclofen intrathecal injection, surgery and serial casting.^8–12 Nerve block with botulinum toxin-A (BTX-A) is considered to be one of the optimal approaches for spastic cerebral palsy due to its rapid effect, great selectivity and few side-effects, ¹³ but the duration of its action is limited and few studies have investigated its long-term effects. ¹⁴

The aim of the present study was to perform a long-term observation of BTX-A block (with and without rehabilitation training) for the treatment of spastic cerebral palsy, in order to analyse the long-term rehabilitative efficacy.

Patients and methods

Study population

The study recruited in- and outpatients aged 1–23 years, with spastic cerebral palsy and high gastrocnemius and soleus muscle tension, who underwent nerve block between July 2005 and November 2011 at the Capital Medical University School of Rehabilitation Medicine, Beijing, China. Inclusion criteria were the ability to walk >10 steps with or without assistance, and tiptoe posture caused by spasticity of gastrocnemius and soleus. Patients with contracture of the calcaneal tendon, epilepsy or allergies were excluded from the study.

Diagnosis and clinical classification of cerebral palsy was performed in accordance with standards formulated by the 2005 Executive Committee for Cerebral Palsy in Children. ¹⁵ Patients were randomly assigned to one of two groups according to a computer-generated randomization schedule: experimental group, BTX-A nerve block followed by ≥2 h/day rehabilitation at home or in hospital; control group, BTX-A nerve block followed by <2 h/day rehabilitation. Muscle tension and motor function were assessed prior to block, using the Modified Ashworth Scale (MAS) ¹⁶ and gross motor function measure (GMFM), ¹⁷ respectively.

The Medical Ethics Committee of China Rehabilitation Research Centre, Beijing, China, approved the study protocol. All patients or their guardians provided written informed consent.

Nerve block

The calf triceps muscle (gastrocnemius and soleus) was treated in all patients. Disposable insulated nerve-block needles, conductive paste, surface electrodes, wires and stimulators were provided by Shanghai Huayi Electronic Instrument Factory, Shanghai, China. The projection area of the selected muscle was determined according to anatomical location and the stimulator anode was fixed with adhesive tape to the skin over the contralateral antagonist. Pulse frequency was set to 3 Hz, with current at 10–15 mA. The cathode was moved around the projection area and the current intensity was adjusted to define the position where muscles were stimulated to maximum contraction with minimum current (blocking point). A stimulation current of 3 mA and pulse frequency of 3 Hz were then used. The skin was disinfected and an insulated needle was connected to the stimulator cathode, then inserted into subcutaneous tissue at the blocking point. Needle depth and current intensity were adjusted to achieve optimal stimulation of muscle contraction using minimum current.

The BTX-A dose was determined according to degree of muscle tension (MAS) and body weight: 5–7 IU/kg if MAS grade 1 or 1+; 7–9 IU/kg if MAS grade 2 or 3. BTX-A (Lanzhou Institute of Biological Products, Lanzhou, China) was diluted to 50 IU/ml with saline before use and injected into 4–6 points on the calf muscle.

Follow-up

Muscle tension was evaluated weekly. BTX-A action time was defined as the length of time from block to reduction in MAS score, and duration of action as the time from block to when MAS scores returned to pre-block levels. Motor function was assessed at 1 year post-block.

Statistical analyses

Data were expressed as mean ± SD. Normality of distribution was confirmed using the one-sample Kolmogorov–Smirnov test. The paired sample t-test was used for intragroup comparisons and the independent sample t-test was used for intergroup comparisons. All statistical analyses were performed with SPSS® software, version 13.0 (SPSS Inc., Chicago, IL, USA). A P-value ≤ 0.05 was considered statistically significant.

Results

The study included 244 patients (159 outpatients/85 inpatients; 154 males/90 females; mean age 6.35 ± 2.76 years; age range 1–23 years), who were divided between the experimental group (n = 120; 79 males/41 females; mean age 5.88 ± 3.95; body weight 20.9 ± 6.35 kg) and the control group (n = 124; 75 males/49 females; mean age 7.13 ± 4.14; body weight 23.2 ± 7.51 kg). There were no significant between-group differences in patient age or body weight.

There were no significant between-group differences in BTX-A action time (experimental group 3.86 ± 1.91 days versus control group 3.33 ± 1.67 days) or duration of action (experimental group 25.57 ± 8.31 weeks versus control group 24.55 ± 7.55 weeks).

Data regarding pre- and post-block MAS and GMFM scores are shown in Table 1. There were no between-group differences in pre-block MAS and GMFM scores. In both groups, MAS scores were significantly lower at 1 month post-block (P < 0.01 for each comparison) and GMFM scores were significantly higher at 1 year post block (P < 0.01 and P < 0.05 for experimental and control groups, respectively) compared with baseline. The experimental group had a significantly greater improvement in GMFM score than the control group (P < 0.01; Table 1).

Table 1.

Muscle tension and motor function in patients with spastic cerebral palsy, before and after botulinum toxin type A nerve block, stratified according to daily duration of post-block rehabilitation.

Parameter	Experimental group ≥2h/day n = 120	Control group <2h/day n = 124
Muscle tension, MAS
Pre-block	2.56 ± 1.03	2.69 ± 1.14
1 month post-block	1.58 ± 0.51 a	1.62 ± 0.61 a
Motor function, GMFM
Pre-block	45.7 ± 8.48	44.5 ± 9.12
1 year post-block	60.9 ± 10.62 a	56.0 ± 9.01b
Improvement	15.2 ± 3.45c	11.5 ± 3.22

Data presented as mean ± SD.

MAS, Modified Ashworth Scale; ¹⁶ GMFM, gross motor function measure. ¹⁷

a

P < 0.01 vs pre-block, ^bP < 0.05 vs pre-block, ^cP < 0.01 vs control group; paired sample t-test for intragroup comparisons and independent sample t-test for intergroup comparisons.

Discussion

Muscle spasms are responsible for delayed motor development and abnormal posture in patients with cerebral palsy.^5,6,8 High tension in the calf triceps muscle results in abnormal posture (such as equinovarus foot), which can be corrected by relief of muscle spasm. ¹⁸ BTX-A injection into the calf triceps muscle has been shown to reduce muscle tension and expand joint activity signficantly,^19,20 and to improve gait and movement.^21,22 BTX-A block was effective for relieving spasms in patients without tendon contracture in the present study, in concurrence with previous reports that BTX-A block and serial casting should be applied in combination (to expand the range of motion in patients with contracture).^23,24

The efficacy of BTX-A blocking has been shown to last for 5–6 months,²⁵ allowing for spasm relief and rehabilitation. Rehabilitation has also been shown to relieve spasms as patients learn correct posture and movement, generating correct movement patterns in the brain and developing their gross motor function.^26,27 Patients in the present study maintained motor function even after BTX-A efficacy ceased (5–6 months post-block). Others have shown that muscle spasms in children with cerebral palsy were significantly reduced (compared with baseline) at 3 months after BTX injection, but not at 6 months. ²⁵ In addition, GMFM scores were significantly improved at 3 and 6 months post-block, similar to the findings of others.^28,29

A retrospective study on the correlations between spasm, muscle strength and motor function in children with cerebral palsy found no relationship between GMFM score and spasm, suggesting that spasm is not related to motor function. ³⁰ Calf muscle tension returned to pre-block levels after 5–6 months in the present study, but GMFM scores remained higher than baseline 1 year after block in both groups. These data suggest that BTX-A block exerts long-term positive effects on function that are independent of the effect of rehabilitation.

Rehabilitation had a significant effect on GMFM scores in the present study, with ≥2h rehabilitation per day resulting in significantly higher scores at 1 year post-block than <2h/day. These data are consistent with findings that demonstrate that BTX injections should be combined with rehabilitation. ³¹

In conclusion, BTX-A nerve block significantly relieves spasticity in patients with cerebral palsy, and the efficacy of this procedure is improved when combined with rehabilitation. Further studies are required, to determine the ideal rehabilitation programme following nerve block.