Adductor spasticity in children with cerebral palsy and treatment with botulinum toxin type A: the parents' view of functional outcome

Botulinum toxin type A (BTX-A) has been used successfully to manage spasticity in children with cerebral palsy. Little has been done to evaluate treatment outcome and satisfaction from the patients' and parents' points of view. The aim of this study was to investigate the parents' perceptions of the benefits of BTX-A on movement disorders in children with cerebral palsy. Twenty-six children with adductor spasticity were enrolled into an open-label, prospective study. Patients received intramuscular injections of BTX-A, and assessments of joint mobility (passive range of motion), degree of spasticity (Modified Ashworth Scale) and functional benefit (Gross Motor Function Measure) were made before and 12–18 weeks after treatment. Parents' assessment of treatment outcomes were evaluated using a standardised questionnaire. BTX-A was shown to be effective in reducing muscular hyperactivity and functional limitations. Parents' satisfaction with the treatment outcome was high. For non-ambulatory patients, the reported benefits included facilitation of daily care, ease of positioning and reduction of pain. For patients who were disabled to a lesser extent, improvements in gait and posture included sitting with improved comfort, standing for longer periods of time and/or walking longer distances. The parents' responses supported the impressions of the therapists, demonstrating that BTX-A produced beneficial effects on daily activities, according to both objective measures and parents' observation.     

Functional improvement in cerebral palsy patients treated with botulinum toxin A injections – preliminary results

Authors report the preliminary results of an open-label, prospective study to evaluate a functional benefit of botulinum toxin type A injections in diparetic cerebral palsy patients, using gross motor function measure (GMFM) score. In a group of 14 children (mean age 3.9 years, range 2-6) treated with Dysport 30 IU/kg, a statistically significant improvement (P < 0.05) was noticed in both simple measurements (Modified Ashworth Scale, Selective Motor Control, Passive Range of Movements, Physician Rating Scale and parental Clinical Global Impression) and complex functions (GMFM dimensions D and E) after 1 and 3 months. However, the simple measurement scores decreased (but not to the baseline) after 3 months; surprisingly, GMFM scores were still increasing (7.7% change after 3 months and 11.3% change after 6 months in nine patients). These results are in concordance with a few other data published to date. The study may support the concept of persistent functional gain in long-term treatment of spasticity caused by cerebral palsy with botulinum toxin type A.     

Outcome measurement of effectiveness of botulinum toxin type A in children with cerebral palsy: an ICIDH-2 approach

The ICIDH-2 serves as a useful framework for differentiating measurement by dimensions of the disabling process. Such differentiation is important to achieve more valid measurement of health related outcomes. We have attempted to examine one intervention, treatment with botulinum toxin type A, for one patient population, children with cerebral palsy, and to describe the outcome measures used in the evaluation of that intervention using this evolving classification system. This process supports the concept that measurement of health outcomes should focus on the nature and extent of functional limitations in physical, social and psychological domains. The selection of measurement outcomes must be determined not only by the requirements of the scientific process but also by the needs of the patients who are the intended beneficiaries of the intervention.     

A randomized study of combined botulinum toxin type A and casting in the ambulant child with cerebral palsy using objective outcome measures

It is recognized that objective gait analysis is of great value in planning a multilevel botulinum toxin type A (BTX-A) treatment. After BTX-A treatment, objective outcome measures can provide new and interesting information for each individual child with cerebral palsy (CP). Moreover, by studying group results, we may evaluate our treatment hypotheses. The present prospective study attempts to document the effect of integrated multilevel BTX-A treatment on objective gait parameters and to define the optimal strategy for the combined treatment of BTX-A with casting in children with cerebral palsy. Objective three-dimensional gait analysis (3DGA) data were collected pre- and 2 months post-treatment, in two randomized patient groups: a first group of 17 children treated with lower leg casting prior to BTX-A injections, and a second group of 17 patients who received casting immediately after injections. The present study demonstrates that improved gait can be achieved after a multilevel BTX-A treatment, combined with casting, using a set of 90 gait parameters. The most pronounced improvement was seen at the ankle joint. The results in the knee, hip and pelvis imply that multilevel treatment of the child with CP should start at an early age, in order to prevent development of muscle contractures. Slightly more pronounced benefits, mainly in the proximal joints, were seen for the children who were casted after injections as compared to the children who were casted before injections.     

Objective measurement of clinical findings in the use of botulinum toxin type A for the management of children with cerebral palsy

Clinicians use a range of clinical and objective measures to quantify the positive and negative features (impairments) of the upper motor neurone syndrome. These measures play an important role in the assessment and selection of suitable candidates for intervention and monitoring of outcome. Intervention strategies often focus on the positive features; however, outcome may be more contingent upon the severity of the negative features. The clinical protocol for patient selection and treatment used by our multidisciplinary team is presented, together with details of the assessment procedure. Measurement tools in routine use are described, including: the Modified Ashworth Scale, the Modified Tardieu Scale ('R1'), muscle length by joint range of motion 'R2', three-dimensional gait analysis, assessments of strength by the Medical Research Council Scale, Selective Motor Control, the Gross Motor Function Measure and the Observational Gait Scale. Three case studies of children with cerebral palsy who underwent botulinum toxin type A treatment as part of their management of gait disorder are presented, a 2-year-old girl with mild hemiplegia ('true equinus'), a 3-year-old boy with moderate hemiplegia ('apparent equinus') and a 6-year-old girl with diplegia, where a targeted approach was used to treat a distal problem and resulted in correction Of a proximal problem.     

The use of botulinum toxin type A in children with cerebral palsy: a retrospective study

The dosage and safety of botulinum toxin type A (BTX-A) treatments in 104 children with cerebral palsy were examined in a retrospective chart review of a 2-year period at Texas Scottish Rite Hospital for Children. Almost all of the BTX-A injections were to the muscles of the lower limbs. The average dose of BTX-A was 8–9 Ukg body weight and the interval between injections averaged 3–5 months. The average total amount of BTX-A injected at a single visit ranged from 146 to 186 U. The safety record for these treatments was excellent, with only 14 adverse events reported in 257 patient injection visits. The most commonly reported adverse event was muscle weakness, which is related to the pharmacology of BTX-A treatment     

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.     

Muscle histopathology in children with spastic cerebral palsy receiving botulinum toxin type A

Introduction: Botulinum toxin A (BoNTA) is routine treatment for hypertonicity in children with cerebral palsy (CP). Methods: This single‐blind, prospective, cross‐sectional study of 10 participants (mean age 11 years 7 months) was done to determine the relationship between muscle histopathology and BoNTA in treated medial gastrocnemius muscle of children with CP. Open muscle biopsies were taken from medial gastrocnemius muscle and vastus lateralis (control) during orthopedic surgery. Results: Neurogenic atrophy in the medial gastrocnemius was seen in 6 participants between 4 months and 3 years post‐BoNTA. Type 1 fiber loss with type 2 fiber predominance was significantly related to the number of BoNTA injections (r = 0.89, P < 0.001). Conclusions: The impact of these changes in muscle morphology on muscle function in CP is not clear. It is important to consider rotating muscle selection or injection sites within the muscle or allowing longer time between injections. Muscle Nerve 53: 407–414, 2016     

Upper limb function after botulinum toxin A treatment in cerebral palsy: Two years follow-up of six cases

The objective of this study was to investigate the effects of botulinum toxin A (BTXA) treatment on impairment and function of the upper limb during a 2-year follow-up period. A prospective longitudinal study design with assessments before and after intervention was utilized, involving six patients with cerebral palsy (three boys and three girls) aged 3 years 4 months to 11 years 11 months at commencement of study. The outcome measures were spasticity (modified Ashworth, MAS), active and passive range of movement (ROM), grips (pinch, key grip, 3-finger grip, narrow cylinder grip, wide cylinder grip, pen grip and diagonal grip; grasping, releasing; pronation-supination), bimanual functions, fine motor functions (Melbourne Assessment of Unilateral Upper Limb Function), movement pattern (Upper Limb Physician's Rating Scale, ULPRS), functional skills and self-care capability (Paediatric Evaluation of Disability Inventory, PEDI), upper extremity use (House Classification) and cosmetic appearance. The assessments were repeated by the same examiners at baseline and at 1, 3 and 6 months after each BTXA treatment and then every 6 months until 24 months. One subject received a total of four injections (at 0, 6, 12 and 18 months), one two injections (at 0 and 12 months) and four one injection at the beginning of the study period. Upper extremity surgery was performed on two subjects during the study and one was operated on 2 months after completion of the study. All children benefited from the BTXA treatment in terms of reduction in muscle tone and increase in active and passive ROM. By 6 months, spasticity returned, but in four children passive and especially active ROM remained better than at baseline. No significant changes in grips, bimanual tasks or Melbourne Assessment scores were detected. The change in movement pattern (ULPRS) was maintained for 3 months in two children and beyond this in four, thus extending beyond the pharmacologic effects of botulinum toxin A. All but one child showed improvement in PEDI functional skill and caregiver assistance scale scores during the 2-year period. The House classification showed a one-grade improvement in one child at 1 month and in one child at 3 months and a three-grade improvement in one child at 3 months after BTXA treatment. After each treatment, the parents reported at least a one-grade improvement in cosmetic appearance in all children at 1 month and in four children maintained at least until 6 months. In two subjects operated during the study period, a distinct improvement in active and passive ROM and a two-grade improvement in the House classification were observed after the operation. In this limited series, the reduction in muscle tone after BTXA treatment did not translate into better gripping or quality of fine motor functions (Melbourne Assessment) of the affected hand, but seemed to have a positive effect on upper limb movement pattern (ULPRS), upper extremity use (House Classification) and cosmetic appearance. Assessment of upper limb function in a child with cerebral palsy demands a variety of measures.     

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.     

The effect of botulinum toxin type A injections on the natural history of equinus foot deformity in paediatric cerebral palsy patients

Neuromuscular blockade with botulinum toxin type A (BTX-A) injections was employed to manage equinus foot deformity in the lower extremities of paediatric cerebral palsy patients. The patients were followed to evaluate the effect of the blockade on lower extremity function and to determine the effect of treatment on the need for tendo-Achilles lengthening (TAL) surgery. The average length of follow-up was 3.4 years. Of the 48 patients, 17 (35%) responded to treatment witbin 6 months of initiation of therapy, as determined by a Physician Rating Scale of gait. Overall, 25 (52%) of the 48 patients underwent TAL surgery during the follow-up period, including eight patients who responded to the BTX-A treatment. The average age of the patients at the time of surgery was 7 years. This age compares favourably with the age at surgery reported in the recent literature. There were no significant differences by responder status, age, or gender in those patients who did and did not require TAL surgery. No adverse events relating to BTX-A were reported. These results indicate that patients who respond to BTX-A treatment have improved physical functioning and gait, and are able to sustain these results long term.     

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.     

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.     

The use of botulinum toxin type A in spastic diplegia due to cerebral palsy

Spastic diplegia is a severely disabling condition and many current treatment options offer the patient no real therapeutic benefit. Intramuscular injection of botulinum toxin type A (BTX-A) has demonstrated the ability to decrease spasticity, improve mobility and delay the need for surgery in patients with spastic diplegia. The study described here was a pilot to a larger study and it aimed to identify the most suitable and sensitive outcome measures to detect the benefits of BTX-A injection. Five adolescents with hip spasticity due to cerebral palsy were injected with BTX-A into the psoas major muscle (for thigh adduction problems) or the soleus muscle (to correct 'toe clawing'). Assessments of gait and mobility were carried out every month for the 4-month study period. Following injection with BTX-A, improvement in patient mobility was most evident in subjects with thigh adduction problems. A reduction in 10-m walking time and an increase in stride length was also more pronounced in patients injected in the psoas. Three of the five patients treated demonstrated an improved Modified Ashworth Scale score at the end of the 4-month observation period. The results conclude that spastic diplegics with problems related to the hip, may benefit from BTX-A. Patients who experience 'toe clawing' present different problems and the measures used did not pick up on the benefits gained by the patients.     

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.     

Botulinum toxin type A management of spasticity in the context of orthopaedic surgery for children with spastic cerebral palsy

Cerebral palsy is the most common cause of physical disability affecting children in developed countries. Although cerebral palsy is, by definition, a 'static encephalopathy' the associated musculoskeletal pathology is progressive and current definitions are therefore somewhat inadequate. Understanding the stages of the musculoskeletal pathology is fundamental to understanding current management strategies, including spasticity management, strengthening programmes and deformity correction by orthopaedic surgery. In this review, a number of new management strategies are described, in which spasticity management by intramuscular injections of botulinum toxin type A and deformity correction, by orthopaedic surgery, are combined.     

The influence of physical therapy and anti-botulinum toxin antibody on the efficacy of botulinum toxin-A injections in children with spastic cerebral palsy

Objective: To identify factors associated with the efficacy of botulinum toxin-A (BoNT-A) injections. Methods: Thirty-eight children with spastic cerebral palsy (CP) received BoNT-A injections into the gastrocnemius. The baseline anti-botulinum antibodies were checked. The Static dorsiflexion range of motion (ROM), Modified Tardieu Scale (MTS) and Physician Rating Scale (PRS) were assessed at pre-injection as well as 4- and 12-week post-injection. Results: No samples contained anti-botulinum antibodies. Greater baseline MTS dynamic range was associated with greater changes in MTS dynamic ranges at 4-week post-injection. More frequent physical therapy was associated with greater changes in static dorsiflexion ROM at 4-week post-injection and greater changes in PRS at 4- and 12-week post-injection. Conclusion: The improvement in PRS at 12-week post-injection was associated with the frequency of physical therapy. Therefore, intensive physical therapy programs may be necessary to maintain the beneficial effects of BoNT-A injections in children with 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.