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.     

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.     

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.     

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 treatment of hip and thigh spasticity: a technique for injection of psoas major muscle

Spasticity of the hip and thigh can result from spinal cord injury, multiple sclerosis, cerebral palsy and numerous other neurological conditions. Chronic hip spasticity causes the patient extreme difficulty in walking and maintaining a comfortable posture. First-line treatment usually consists of oral anti-spastic agents, although these are often associated with a high side-effect burden. intramuscular injections of botulinum toxin type A (BTX-A), particularly into the psoas major muscle, have proved to be of functional benefit to the patient. A highly reliable and reproducible method for injecting the psoas major muscle through a para-spinal route has been developed to reduce the power of the muscle and hip flexion deformity. Injection occurs through the middle of the erector spinae muscle at L2, L3 and L4, delivering a total of 150 U BTX-A to the psoas major muscle. Follow-up with a substantial rehabilitation programme reliably ensures a decrease in Modified Ashworth Scores and improvements in the outcome assessment scores measured.     

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.     

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.     

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.     

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.     

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.     

Effect of multilevel botulinum toxin a and comprehensive rehabilitation on gait in cerebral palsy

To evaluate the effect of multilevel botulinum toxin A and comprehensive rehabilitation on gait pattern, muscle length, and spasticity, a multicenter randomized trial was performed in 46 children with spastic cerebral palsy who walk with flexed knees. Their mean age was 8.0 years (range 4 to 11 years). They were randomly allocated to the intervention group (multilevel botulinum toxin A and comprehensive rehabilitation) or the control group (usual care). After 6 weeks, a significant treatment effect in the intervention group was observed on: improved knee extension during midstance and terminal swing (7 degrees and 5 degrees , P < 0.01, respectively); hip rotation during terminal swing (4 degrees , P = 0.02); gait score (1.7, P < 0.01); decreased spasticity in hamstrings (11 degrees , P < 0.01), gastrocnemius (6 degrees , P = 0.01), and soleus (5 degrees , P = 0.02); and increased muscle length in hamstrings (9 degrees , P < 0.01) and gastrocnemius (5 degrees , P < 0.01). The improved muscle length was maintained up to 24 weeks. This study demonstrated that multilevel botulinum toxin A and comprehensive rehabilitation improves knee extension during gait, increases muscle length, and decreases spasticity in injected muscles after 6 weeks in children who walk with flexed knees. Although the effect on muscle length was maintained after 24 weeks, the effect on gait and spasticity had disappeared.     

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.     

Double-blind comparison study of two doses of botulinum toxin A injected into calf muscles in children with hemiplegic cerebral palsy

Despite several trials showing reductions in tone and improvements in gait, the relation between botulinum toxin A (BTX-A) dose and response has rarely been investigated. A double-blind randomized comparison of two doses of BTX-A in children with spastic hemiplegic cerebral palsy (n=48, mean age 7 years 6 months, range 3 to 15 years) was undertaken. The two doses selected were representative of the lower and the higher doses used in clinical practice (24 units/kg body weight and 8 units/kg body weight). Using gait analysis we evaluated hip, knee, and ankle joint kinetics and sagittal kinematics throughout the gait cycle. Gastrocnemius muscle length was calculated at each visit using the method described by Eames and used as our primary outcome measure. Our secondary outcome variable was maximum ankle angle measured during stance and swing phases. In summary, we found that there were indications that 24 units/kg body weight was more effective and lasted longer than 8 units/kg. Analysis in terms of absolute dose suggested that the dose-response correlation was non-linear, and that the optimal range lay between 200 and 500 units BTX-A (Dysport).     

Ultrasound-guided botulinum toxin injection technique for the iliopsoas muscle

Intramuscular botulinum toxin A injections are beneficial for the treatment of functional shortening of the iliopsoas muscle, but it is difficult to achieve precise needle positioning and injection. As a solution to this we present an ultrasound-guided injection technique for the iliopsoas muscle using an anterior approach from the groin. The procedure was performed 26 times in 13 patients (seven males, six females; mean age 11 years, SD 9 years 8 months; age range 4 to 31 years), 10 times bilaterally. Indications were functional iliopsoas shortening due to cerebral palsy (17 hips), hereditary spastic paraplegia (four hips), and Perthes disease (five hips). In all cases the iliopsoas muscle was identified easily by ultrasound; the placement of the injection needle and injection into the site of interest were observed during real time. No complications were encountered. Botulinum toxin A (BTX-A) injections have become established as a standard procedure for the treatment of functional shortening of different muscles in persons with spasticity or dystonia (Kessler et al. 1999, Bakheit et al. 2001, Kirschner et al. 2001). Optimal needle placement is essential to avoid severe side effects and to assess lack of response to the drug or incorrect region of injection. While injection into superficial, very palpable muscles is quite easy, the approach to other muscles such as the iliopsoas muscle may be more difficult and the placement of the needle for an optimal injection site is harder to control. As a solution to this, we present an ultrasound-guided injection technique. The main indications for BTX-A injections in the iliopsoas muscle are dynamic hip flexion deformities mostly due to spastic conditions which may compromise walking (increased anterior pelvic tilt during the whole gait cycle, decreased hip extension at terminal stance, increased peak hip flexion during swing; Molenaers et al. 1999. Another indication might be decentration of the femoral head (as part of an injection programme which also includes other muscles like the adductors and the medial hamstrings) for pain relief, reducing care difficulties and, possibly, prevention of further decentration (Porta 2000, Foster et al. 2001, Deleplanque et al. 2002, Lubik et al. 2002). In Perthes disease, BTX-A injections in the iliopsoas muscle and the adductors may prevent a fixed deformity, which is a negative prognostic factor.     

Effects of ultrasound-guided botulinum toxin type-A injections with a specific approach in spastic cerebral palsy

The aim of this study was to detect effects of ultrasound-guided botulinum toxin type-A (US-guided BoNT-A) injections prepared according to lower extremity innervation zones on spasticity and motor function in 3–16 years children with diplegic and hemiplegic spastic cerebral palsy. This study included 25 patients between 3 and 16 years of age who admitted to our clinic in 2017, were being followed in our clinic with a diagnosis of cerebral palsy, had BoNT-A injections due to lower extremity spasticity. The US-guided BoNT-A injections were administered into the spastic muscles using a specific approach according to innervation zones of muscle. Modified Ashworth Scale (MAS) and Gross Motor Functional Classification System (GMFCS) were assessed at the baseline, and 4 and 12 weeks after the BoNT-A injections. Minimum and maximum ages of the patients were 45 and 192 months, and gender distribution was 8 females and 17 males. Significant decreases in the MAS scores of the knee and ankle tones were measured 4 and 12 weeks after the BoNT-A injection when compared to the baseline scores (p?<?0.025). Hip muscle tonus only decreased 12 weeks after the injection (p?<?0.025). In parallel with a reduction in spasticity GMFCS improved from 3 to 2 in the 4th and 12th weeks. US-guided BoNT-A injections with Euro-musculus approach is a practical and effective method to perform injections into proper points of proper muscles in children with spastic cerebral palsy.     

Muscle strength training to improve gait function in children with cerebral palsy

The aim of the study was to investigate the influence of muscle strength training on gait outcomes in children with cerebral palsy. Sixteen children (two females, 14 males, Gross Motor Function Classification System levels I-II, mean age 12y 6mo, range 9y 4mo-15y 4mo) underwent muscle strength measurement using a handheld device, Gross Motor Function Measure (GMFM) assessment, three-dimensional gait analysis, joint range of motion assessment, and grading of spasticity before and after 8 weeks of training. All participants had a diagnosis of spastic diplegia and could walk without aids. Training consisted of exercises for lower extremity muscles with free weights, rubber bands, and body weight for resistance, three times a week. Values for muscle strength below normal were identified in all children; this was most pronounced at the ankle, followed by the hip muscles. After training, muscle strength and GMFM scores increased, velocity was unchanged, stride length increased, and cadence was reduced. There was an increase in hip extensor moment and power generated at push off. Eight weeks of muscle strength training can increase muscle strength and improve gait function.     

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.     

Botulinum toxin treatment in cerebral palsy: evidence for a new treatment option

Intramuscular injections of botulinum toxin type A (BTX-A) have increasingly been used to reduce spasticity in specific muscle groups in children with cerebral palsy. Targets of therapeutic efforts are improvement of gross motor function, alleviation of pain or facilitation of hygienic care. Placebo-controlled studies have shown the local and functional effectiveness of BTX-A for the treatment of dynamic pes equinus. Whether long-term treatment with BTX-A improves motor development and delays contractures is still under investigation.     

AACPDM systematic review of the effectiveness of therapy for children with cerebral palsy after botulinum toxin A injections

The aim of this review was to assess the effectiveness of therapy interventions on improving outcomes in children with cerebral palsy (CP) who have received botulinum toxin A (BTX-A) injections to either upper or lower limb muscles. We searched: the Cochrane Central Register of Controlled Trials; the electronic databases Medline, EMBASE, CINAHL, PEDro, SCI, and SSCI; websites of professional associations; and reference lists in trial reports and other relevant articles. We used studies on the effect of therapy on motor control, functional abilities, contracture, spasticity, and/or pain as the selection criteria. Methodological quality and the strength of evidence was assessed systematically by three independent raters using American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) guidelines. Twenty-four papers met the criteria for inclusion in the content analysis of evidence. Of these, only one randomized controlled trial was available, with results demonstrating that electrical stimulation postinjection did not enhance the effects of BTX-A on gait improvement (insufficient data provided to report size of effect). Remaining papers were of level II evidence (n=2), Level IV evidence (n=5), and level V evidence (n=14). We conclude that there is insufficient evidence to either support or refute the use of therapy interventions after BTX-A injections in children with CP.     

Botulinum toxin treatment in cerebral palsy: evidence for a new treatment option

Intramuscular injections of botulinum toxin type A (BTX-A) have increasingly been used to reduce spasticity in specific muscle groups in children with cerebral palsy. Targets of therapeutic efforts are improvement of gross motor function, alleviation of pain or facilitation of hygienic care. Placebo-controlled studies have shown the local and functional effectiveness of BTX-A for the treatment of dynamic pes equinus. Whether long-term treatment with BTX-A improves motor development and delays contractures is still under investigation.