Single event multilevel botulinum toxin type A treatment and surgery: similarities and differences

The present study attempts to provide objective evidence of two treatment options for children with cerebral palsy (CP): multilevel botulinum toxin type A (BTX-A) injections and multilevel surgery. The purpose of the study was to clarify the differences and the similarities, and common treatment principles of both treatment strategies. Objective three dimensional gait analysis data were studied retrospectively in two patient groups pre- and post-treatment (randomly selected from a group of children that were treated between 1998 and 1999). In the first group, 29 children with CP were managed with BTX-A injections according to an integrated multilevel approach ( Molenaers et al ., 1999a ). A second group of 23 children with CP were managed by a more traditional single event multilevel surgery, also according to an integrated approach. Our aim was to evaluate the differences as well as the similarities between both patient groups, using a set of 56 parameters selected from three-dimensional gait analysis. The unifying concept between management with BTX-A injections and orthopaedic surgery was the adoption of a multilevel approach at one session. The groups demonstrated considerable differences with respect to age, pretreatment condition and amount and level of improvement after treatment. The children who received BTX-A were typically younger, and showed primary gait problems in the distal joints, whereas the children who underwent surgery demonstrated a higher frequency of gait deviations in the transverse plane and had more complications. Although the benefit of both treatments was confirmed by the present study, a difference in the amount and level of improvement was also demonstrated. In conclusion, these treatment modalities should be regarded as complementary rather than mutually exclusive treatments, with both calling for an integrated approach.     

A multilevel approach to botulinum toxin type A treatment of the (ilio)psoas in spasticity in cerebral palsy

In spasticity, flexion deformity of the hip is frequently associated with contracture or hyper-reflexia of the psoas muscle. Botulinum toxin type A (BTX-A) has been used for some considerable time in the management of paediatric gait disorders. We have been using a multilevel approach to manage spasticity in cerebral palsy for several years, the combination of gait analysis and clinical evaluation being important for the selection of target muscles for BTX-A injections. Twenty cerebral palsy children (12 female) with spasticity were treated with BTX-A injections (BOTOX® mean dose, 2 U/kg body weight) into the psoas muscle. Patients were monitored using range of motion measurements of maximal hip extension, clinical estimates of hypertonia in the hip flexors, gait analysis (three-dimensional kinematics and kinetics) and surface electromyography of major lower limb muscles. Full gait analysis was carried out on 12 of the patients. Significant clinical improvements were observed following 15 of the 21 psoas treatments. Furthermore, the kinematics results of gait analysis showed improvement in one or more parameters in nine of the 12 patients. In conclusion, we have demonstrated the value of a multilevel approach to BTX-A treatment in the management of spasticity in children with cerebral palsy.     

Motor function following multilevel botulinum toxin type A treatment in children with cerebral palsy

This study evaluated the effects of multilevel botulinum toxin type A (BTX-A) treatments on the gait pattern of children with spastic cerebral palsy (Gross Motor Function Classification System Levels I-III). In this nested case-control design, 30 children (mean age 6y 11mo [SD 1y 5mo]; 21 males, nine females; 19 with hemiplegia, 11 with diplegia) were treated according to best practice guidelines in paediatric orthopaedics, including BTX-A injections. A matched control group of 30 children (mean age 7y 8mo [SD 1y 10mo]; 13 males, 17 females; 19 with hemiplegia, 11 with diplegia) were treated identically, but without BTX-A. Motor development status at 5 to 10 years of age was assessed by means of three-dimensional gait analysis at a mean time of 1 year 10 months (SD 10mo) after the last BTX-A treatment. The control group showed a significantly more pronounced pathological gait pattern than the BTX-A group. Major differences were found for pelvic anterior tilt, maximum hip and knee extension, and internal hip rotation. These results provide evidence for a prolonged effect of BTX-A and suggest that BTX-A injections, in combination with common conservative treatment options, result in a gait pattern that is less defined by secondary problems (e.g. bony deformities) at 5 to 10 years of age, minimizing the need for complex surgery at a later age and enhancing quality of life.     

Botulinum toxin type A treatment of cerebral palsy: an integrated approach

We have applied a multilevel approach to the management of spasticity associated with cerebral palsy (CP). All of the following factors are important in forming an integrated strategy for botulinum toxin type A (BTX-A) therapy: the timing of injections, patient selection, multilevel BTX-A treatment, optimal dosage and injection technique, follow-up treatment and objective measurements of functional outcome. Data on all these factors are presented here. CP patients had a mean age of 6.5 years (n = 315), and the dose of BTX-A (BOTOX®) ranged from 2 to 29 U/kg body weight ( n = 156). The combination of muscles injected in our multilevel approach differed for patients with diplegia, hemiplegia and quadriplegia: patients with hemiplegia received injections in the gastrocnemius and medial hamstrings; this combination was extended to the adductors for patients with diplegia and quadriplegia ( n = 156). For patients with quadriplegia, muscles in a three-level (gastrocnemius, medial hamstrings, adductors and iliopsoas) or two-level (excluding the gastrocnemius) combination were also frequently injected. The duration of effect of BTX-A treatment was mainly determined by follow-up treatment consisting of: serial casting, day and night orthoses and physiotherapy. No major side effects of BTX-A were reported. This integrated approach appears to prolong the duration of BTX-A treatment, resulting in a duration of about 1 year between injections.     

Comparing botulinum toxin A with casting for treatment of dynamic equinus in children with cerebral palsy

The purpose of this study was to compare the cumulative efficacy (three treatment sessions) of botulinum toxin A (BTX-A) alone, casting alone, and the combination of BTX-A and casting in the management of dynamic equinus in ambulatory children with spastic cerebral palsy (CP). Thirty-nine children with spastic CP (mean age 5y 10mo, range 3 to 9y) were enrolled in the study. A multicenter, randomized, double blind, placebo-controlled prospective study was used. Children were randomly assigned to one of three treatment groups: BTX-A only (B), placebo injection plus casting (C), or BTX-A plus casting (B+C). The dosage for the BTX-A injections was 4U/kg per extremity. Assessments were performed at baseline, 3, 6, 7.5, and 12 months with a total of three treatments administered after the evaluations at baseline, 3, and 6 months. Primary outcome measures were ankle kinematics, velocity, and stride length. Secondary outcome measures were ankle spasticity, strength, range of motion, and ankle kinetics. Group B made no significant change in any variable at any time. Groups C and B+C demonstrated significant improvements in ankle kinematics, spasticity, passive range of motion, and dorsiflexor strength. Results of this 1-year study indicate that BTX-A alone provided no improvement in the parameters measured in this study, while casting and BTX-A/casting were effective in the short- and long-term management of dynamic equinus in children with spastic CP.     

Gait analysis to assess the effects of botulinum toxin type A treatment in cerebral palsy: an open-label study in 10 children with equinus gait pattern

Botulinum toxin type A (BTX-A) injections induce a dose-related decrease in muscle tone and increased joint mobility in adults with spasticity and children with cerebral palsy. The aim of this study was to address the question of whether BTX-A-related improvements in joint mobility and muscle tone are associated with changes in instrumental gait analysis in children with cerebral palsy. Ten children with cerebral palsy and equinus gait were given a single dose of BTX-A (5 U BOTOX®/kg body weight per leg) into the gastrocnemius muscles. At follow-up (mean, 32.6 days post-injection), a significant ( P < 0.05) increase in both passive and active ankle range of motion was observed, together with a decrease in the modified Ashworth score. Instrumental gait analysis showed improvements in ankle and knee kinematics as well as in time-distance parameters, with a significant increase in step length observed ( P < 0.05). Semi-quantitative analysis of rectified electromyographic (EMG) recordings of the tibialis anterior muscle during gait showed a reduction in EMG activity during the stance phase and an increase in EMG activity during the swing phase. This study demonstrated the benefits of BTX-A treatment in improving joint mobility and ambulatory function in children with cerebral palsy, and showed that changes in tibial anterior muscle activity as a result of BTX-A injections into the gastrocnemius muscle can be measured by instrumental gait analysis.     

Botulinum toxin and cerebral palsy: time for reflection?

Botulinum toxin A (BTX-A) is increasingly being used in early management of spasticity in ambulant children with cerebral palsy (CP), with the aim of improving function, promoting muscle growth, and delaying the need for surgical intervention. However, there is a lack of evidence about the long-term outcome of BTX-A injections. The focus on spasticity as the predominant problem in younger children with spastic CP may not fully consider the associated muscle weakness. It also raises concern that although BTX-A may improve function in the short term, it has the potential to affect muscle growth and function adversely in the long term. A cautious approach to the early use of BTX-A, with the use of objective outcome measures within a specialized multidisciplinary setting, is recommended, particularly in ambulant children with spastic diplegic CP, until further evidence is available on the long-term outcome of early BTX-A injections in children with CP.     

Current evidence for the use of botulinum toxin type A in the management of children with cerebral palsy: a systematic review

Management of children with cerebral palsy (CP) is the focus of considerable resources in many countries, so that evaluation of the efficacy for new and established treatments is imperative. Botulinum toxin type A (BTX-A) is a relatively new method of spasticity management in children with cerebral palsy. It has been the focus of extensive research since its application to cerebral palsy 10 years ago. In a systematic review relating to the management of the lower limb in cerebral palsy 156 papers were identified. These were categorized according to Sackett and the World Health Organisation International Classification of Impairments, Disabilities and Handicaps model. We identified 10 randomized trials evaluating the use of BTX-A in the lower limb in children with cerebral palsy in a systematic review. A meta-analysis showed the pooled risk difference between BTX-A and placebo in three trials was 0.25 (95% CI 0.13, 0.37) and 0.23 (95% CI −0.06, 0.53) for two trials of BTX-A and casting using the physicians rating scale. These represent moderate treatment effects that are dosage-dependent. Outcomes were also compared for function in five studies. The type of evidence for BTX-A was graded by each treatment indication and directions for future research were then drawn from the available evidence.     

Functional outcomes of multilevel botulinum toxin and comprehensive rehabilitation in cerebral palsy

The objective of this study was to measure the effect of lower extremity multilevel botulinum toxin A injections and comprehensive rehabilitation on spasticity and to determine the functional gains in ambulatory children with cerebral palsy. Sixteen ambulatory children with spastic cerebral palsy (9 hemiplegic, 7 diplegic), aged between 3 and 8 years, who were able to walk with or without assistance (Gross Motor Functional Classification System I-III) were recruited to the study. Botulinum toxin A injections were applied to a total of 23 extremities, followed by a comprehensive rehabilitation program. Walking distance and walking speed (evaluated by the Six-Minute Walk Test) were significantly improved after treatment. Similarly, scores on the Observational Gait Scale (assessed by video gait analysis) increased significantly. Improvements in muscle length, spasticity, and selectivity were recorded. Reduced muscle spasticity after botulinum toxin A injections in children with cerebral palsy, with a comprehensive rehabilitation program, enabled clinically relevant improvements in functional ability.     

Medium-term response characterisation and risk factor analysis of botulinum toxin type A in the management of spasticity in children with cerebral palsy

We prospectively studied the medium-term effects of botulinum toxin type A (BTX-A) treatment in 197 children with cerebral palsy. Between one and four target muscles were selected according to functional goals and biomechanical assessments, and were injected at multiple sites with BTX-A (BOTOX®). The mean total dose administered was 10.5 U BOTOX®/Vkg body weight. In 37% of treatment episodes, children were safely treated with high doses, 12–16 Ukg body weight. Significant improvements were seen in the Modified Ashworth and Tardieu scales at 3 and 12 weeks post-injection, and in muscle length, as determined by joint range of motion, at 3,12 and 24 weeks post-treatment. Significant improvements in gait were noted using the Modified Physicians' Rating Scale, and joint kinematics and kinetics. Forty-five per cent of children were subsequently managed by repeated BTX-A injections, 17% proceeded to single-level soft tissue surgery and 38% proceeded to multi-level surgery after mean intervals of 12.8, 16.4 and 173 months, respectively. Side effects were noted in 10 children (6.2% of total treatment occasions) and included local pain (1.2%), bruising (0.7%), temporary generalised weakness (0.3%), temporary incontinence (1.2%) and pneumonia (1.2%). In summary, BTX-A was safe and effective in the management of spasticity in children with cerebral palsy. Side effects were infrequent, usually minor and self-limiting.