Does botulinum neurotoxin A make walking easier in children with cerebral palsy? A randomized clinical trial.

AIM: To assess the effect of single botulinum neurotoxin A (BoNT-A) injections into the calf muscles on the gross energy cost of walking in children with cerebral palsy (CP) and to evaluate the effect of BoNT-A on walking capacity, physical activity, perceived changes in mobility, and pain. METHOD: This was an industry-independent, randomized, quadruple-blind, placebo-controlled, multicentre trial (ClinicalTrials.gov registration: NCT02546999). Sixty-one children (33 male, median age [range] = 8 years [4-16 years]) with spastic CP and classified in Gross Motor Function Classification System (GMFCS) levels I and II allocated to single injections of either BoNT-A or 0.9% saline into the calf muscles. The main outcome was gross energy cost (J/kg/m); secondary outcomes were walking capacity, habitual physical activity, perceived change in mobility tasks, and calf pain at baseline, 4 weeks (P1), 12 weeks (P2), and 24 weeks (P3) after the injection. RESULTS: The mean change in energy cost did not differ significantly between groups at the primary time point P2 (-0.27 J/kg/m, 95% confidence interval - 0.91 to 0.36, p = 0.404), nor at P1 or P3. Regarding the secondary outcomes, there was some evidence of a larger reduction in pain intensity in the group given BoNT-A (p = 0.043). INTERPRETATION: One treatment with BoNT-A was not superior to placebo in making walking easier in children with CP classified in GMFCS levels I and II, at least in the short term. BoNT-A may have a pain-reducing effect.

Correspondence between Expected, Perceived, and Measured Effects of BoNT-A Treatment in Calf Muscles among Children and Adolescents with Cerebral Palsy: A Mixed Methods Study.

(1) Background: Our study explores the relationship between expected, perceived, and measured effects of botulinum toxin A (BoNT-A) treatment and saline (placebo) in children and adolescents with cerebral palsy (CP) in the calf muscles of 20 children and adolescents with cerebral palsy (CP), aged 4-15 years, using the Gross Motor Function Classification System (GMFCS) I-II. (2) Methods: A mixed methods parallel database design was used. Quantitative and qualitative data were collected at baseline and four weeks after treatment. The primary quantitative measure was gross energy cost (EC) during walking, obtained from a 5-Minute Walk Test (5MWT), while qualitative semi-structured interviews were performed with each parent and child/adolescent individually. (3) Results: Four weeks after treatment, we did not find any correspondence between expected, measured, and perceived effects. Interestingly, parental perceptions of treatment effects were more consistent than the measured outcomes. We also observed a connection between parental treatment expectations and perceived effects, often related to reduced energy expenditure. Children tended to view their parents as treatment experts and had fewer expectations and perceptions themselves. (4) Conclusions: These findings support the importance of child-centered care, which entails actively listening to children's expectations and perceptions during the treatment process.

The relation of energy cost of walking with gait deviation, asymmetry, and lower limb muscle co-activation in children with cerebral palsy: a retrospective cross-sectional study.

BACKGROUND: Compared to typically developing children, children with cerebral palsy (CP) have increased energy expenditure during walking, limiting activity and participation. Insight into whether the also deviating and more asymmetric gait with increased muscle co-activation contributes to this increased energy expenditure is important for clinical decision making. The aim of this study was to investigate the relation between energy cost of walking with gait deviation, asymmetry, and muscle co-activation in children with CP. METHODS: Forty ambulant children with CP, with Gross Motor Function Classification System (GMFCS) level I (N = 35) and II (N = 5), aged between 5-17y, were tested at one or two occasions with 24 weeks in between, resulting in 71 observations. Gross energy cost (J/kg/m) was measured during a 5-min walk test at self-selected speed. From a 3-dimensional gait analyses, kinematic variables and electromyography were extracted to calculate the gait deviation index (GDI) and co-activation index. The relation between energy cost and GDI, GDI asymmetry, and co-activation index of the lower limb muscles was evaluated through mixed model analyses. Height was included to control for growth-related variation. RESULTS: Gait deviation and height combined explained about 40% of the variance in gross energy cost. No significant contribution was found for gait asymmetry or co-activation index. CONCLUSIONS: This cross-sectional study indicates that increased gait deviation contributes to increased energy cost of walking in children with GMFCS level I and II.

Energy cost of gait in children and the effect of speed, age, and body size.

BACKGROUND: Energy cost (EC) of comfortable walking is often used in clinical evaluation of children with altered gait function. EC is presented as energy expenditure per kg bodyweight per meter, either in total (grossEC) or in addition to resting energy expenditure (netEC). GrossEC is considered more reliable and netEC less affected by between-subject variations in speed, age, and body size. However, the effect of the individual child's speed on EC is rarely considered, while altered gait function may affect both speed and EC. RESEARCH QUESTION: To what extent are grossEC and netEC affected by within-subject variation in speed and between-subject variations in speed, age, and body size? METHODS: Forty-two typically developing children (7-15 y) were included in this cross-sectional study. Age, height, and bodyweight were obtained. Breath-to-breath gas-exchange measures of VO2 and VCO2 were conducted during rest and five over-ground gait conditions: walking at slow, comfortable, and fast speed, jogging and running. All conditions lasted 3-5 min. Body surface area, non-dimensional speed, grossEC, and netEC were calculated. Regression analyses and mixed model analyses were conducted to explain the effect of speed, age, and body size on variations in EC. RESULTS: GrossEC showed a non-significant, concave up relation to within-subject variation in speed, with a minimum around comfortable/fast walking speed. NetEC had a strong positive linear relation to within-subject variation in speed. For each gait condition, grossEC was more affected by between-subject variations in speed, age, and body size compared to netEC. However, the effect of age and body size was not eliminated for netEC but was quadratic. SIGNIFICANCE: Although normalised to speed and bodyweight, grossEC and netEC are still affected by those factors. However, they are affected differently for within- and between-subject variations. This must be considered when interpreting EC in children in relation to gait function.

Effects of Ankle-Foot Orthoses on acceleration and energy cost of walking in children and adolescents with cerebral palsy.

BACKGROUND: Impaired postural control is a key feature of cerebral palsy that affects daily living. Measures of trunk movement and acceleration have been used to assess dynamic postural control previously. In many children with cerebral palsy, ankle-foot orthoses are used to provide a stable base of support, but their effect on postural control is not yet understood. OBJECTIVES: The objectives of the current study were to investigate the effects of ankle-foot orthoses on postural control and energy cost of walking in children with cerebral palsy. STUDY DESIGN: Clinical study with controls. METHODS: Trunk accelerometry (amplitude and structure) and energy cost of walking (J/kg/m) were recorded from five-minute walking trials with and without ankle-foot orthoses for children with cerebral palsy and without orthoses for the reference group. RESULTS: Nineteen children with unilateral spastic cerebral palsy and fourteen typically developed children participated. The use of ankle-foot orthoses increased structure complexity of trunk acceleration in mediolateral and anterior-posterior directions. The use of ankle-foot orthoses changed mediolateral-structure toward values found in typically developed children. This change was not associated with a change in energy cost during walking. CONCLUSIONS: The use of ankle-foot orthoses does affect trunk acceleration that may indicate a beneficial effect on postural control. Using measures of trunk acceleration may contribute to clinical understanding on how the use of orthoses affect postural control.

Surface Electromyography Normalization Affects the Interpretation of Muscle Activity and Coactivation in Children With Cerebral Palsy During Walking.

Investigating muscle activity and coactivation with surface electromyography (sEMG) gives insight into pathological muscle function during activities like walking in people with neuromuscular impairments, such as children with cerebral palsy (CP). There is large variation in the amount of coactivation reported during walking in children with CP, possibly due to the inconsistent handling of sEMG and in calculating the coactivation index. The aim of this study was to evaluate how different approaches of handling sEMG may affect the interpretation of muscle activity and coactivation, by looking at both absolute and normalized sEMG. Twenty-three ambulatory children with CP and 11 typically developing (TD) children participated. We conducted a three-dimensional gait analysis (3DGA) with concurrent sEMG measurements of tibialis anterior, soleus, gastrocnemius medialis, rectus femoris, and hamstring medialis. They walked barefoot at a self-selected, comfortable speed back and forth a 7-m walkway. The gait cycle extracted from the 3DGA was divided into six phases, and for each phase, root mean square sEMG amplitude was calculated (sEMG-RMS-abs), and also normalized to peak amplitude of the linear envelope (50-ms running RMS window) during the gait cycle (sEMG-RMS-norm). The coactivation index was calculated using sEMG-RMS-abs and sEMG-RMS-norm values and by using two different indices. Differences between TD children's legs and the affected legs of children with CP were tested with a mixed model. The between-subject muscle activity variability was more evenly distributed using sEMG-RMS-norm; however, potential physiological variability was eliminated as a result of normalization. Differences between groups in one gait phase using sEMG-RMS-abs showed opposite differences in another phase using sEMG-RMS-norm for three of the five muscles investigated. The CP group showed an increased coactivation index in two out of three muscle pairs using sEMG-RMS-abs and in all three muscle pairs using sEMG-RMS-norm. These results were independent of index calculation method. Moreover, the increased coactivation indices could be explained by either reduced agonist activity or increased antagonist activity. Thus, differences in muscle activity and coactivation index between the groups change after normalization. However, because we do not know the truth, we cannot conclude whether to normalize and recommend incorporating both.

Physiological responses during clinical spasticity evaluation in elbow flexors in children with cerebral palsy.

BACKGROUND: The Tardieu test is often used to identify and evaluate the severity of spasticity for clinical decision-making and treatment evaluation in cerebral palsy (CP). Objective: The study's objective was to gain further insight into the construct validity of clinical spasticity evaluation in children with CP. Methods: The kinematics and neuromuscular response of the biceps brachii (BB) during passive elbow extension were studied when performing the Tardieu test with its corresponding clinical interpretation. Fifteen children with unilateral spastic CP and 15 typically developing (TD) peers 15 (median/interquartile range age; 13/4 and 12/5 years, respectively) participated. Results: A clinical catch was detected in 9 of the 15 children with CP. During fast passive elbow extension, the CP group had higher BB activation (p = 0.041), lower fast maximal angular velocity (p = 0.001), and decelerated earlier in the extension movement (p = 0.001). Discussion: On average, the CP group without a clinical detected catch were closer to TD for all those variables, but this only reached statistical 20 significance in the latter variable (p = 0.018). This inconsistency also shows in possibly one false positive and three false negative catch observations. Conclusion: The Tardieu test should be carried out with caution on individual level and more studies including kinematic and neuromuscular measures are necessary.

The Effect of Increased Gait Speed on Asymmetry and Variability in Children With Cerebral Palsy.

Gait of children and adolescents with cerebral palsy (CP) is often reported to be more asymmetric and variable than gait of typically developing (TD) peers. As this may lead to less stable and less efficient gait, a relevant clinical question is how asymmetry may be improved and variability reduced in this population. The main objective of the current study was to investigate whether higher walking speed would affect gait symmetry and gait variability in children and adolescents with CP. Data from clinical gait analyses of 43 children and adolescents (29 males and 14 females) with unilateral (n = 28) or bilateral (n = 15) CP were included. Mean age was 11.3 ± 3.4 years, with level I (n = 26) or level II (n = 17) according to the Gross Motor Function Classification System (GMFCS). Corresponding data from 20 TD peers, matched in age and gender, were included as reference. Step time, step length, single support, and stance phase were studied at two different gait speeds: preferred and fast walking speed. Symmetry index and coefficient of variation were used as measures of asymmetry and variability, respectively. Results indicated that all participants managed to increase gait speed when instructed to do so. Overall, increased speed did not result in a more asymmetrical or variable gait, except for an increase in step length asymmetry and a difference in response between GMFCS levels I and II in variability. This implies that manipulation of gait speed may be useful clinically without necessarily making gait more unstable. However, some increase in step length asymmetry may be inevitable when gait speed is increased in people with CP.

Ventilatory efficiency and aerobic capacity in people with multiple sclerosis: A randomized study.

OBJECTIVES: To assess ventilatory efficiency and aerobic capacity in people with multiple sclerosis and whether treadmill walking or progressive strength training has an effect on these parameters in this population. METHODS: In all, 24 adults with multiple sclerosis with an Expanded Disability Status Scale score of ≤6 completed a cardiopulmonary exercise test before and after 8 weeks of exercise. They were randomized to treadmill walking of low-to-moderate intensity (50%-70% of peak heart rate) or progressive strength training (six repetitions × two at 80% of one repetition maximum). Both groups exercised for 30 min three times per week. Primary outcome measure was ventilatory efficiency measured as the minute ventilation/carbon dioxide production (VE/VCO2) ratio and oxygen uptake efficiency slope. Secondary outcome was aerobic capacity, measured as peak oxygen uptake (VO2peak). RESULTS: Despite low aerobic capacity, ventilatory efficiency was found to be within normal range. After 8 weeks of exercise, no significant between-group differences emerged in (1) VE/VCO2 ratio (26 ± 2.2 to 26 ± 2.0, 29 ± 2.0 to 28 ± 2.3, p = 0.66), (2) oxygen uptake efficiency slope (2697 ± 442 to 2701 ± 577, 2473 ± 800 to 2481 ± 896, p = 0.71), or (3) VO2peak in mL/kg/min (28 ± 4.4 to 30 ± 4.3, 29 ± 6.7 to 29 ± 6.4, p = 0.38) in treadmill walking and progressive strength training, respectively. There were no significant within-group differences either. No adverse events occurred during cardiopulmonary exercise test or exercise training. CONCLUSION: In people with mild-to-moderate multiple sclerosis, 8 weeks of treadmill walking of low-to-moderate intensity or progressive strength training did not have any effect on ventilatory efficiency or aerobic capacity. Although aerobic capacity was lower than reference values, ventilatory efficiency was not reduced.

The WE-Study: does botulinum toxin A make walking easier in children with cerebral palsy?: Study protocol for a randomized controlled trial.

BACKGROUND: Intramuscular injections of botulinum toxin A (BoNT-A) have been a cornerstone in the treatment of spasticity for the last 20 years. In Norway, the treatment is now offered to two out of three children with spastic cerebral palsy (CP). However, despite its common use, the evidence for its functional effects is limited and inconclusive. The objective of this study is to determine whether BoNT-A makes walking easier in children with CP. We hypothesize that injections with BoNT-A in the calf muscles will reduce energy cost during walking, improve walking capacity, increase habitual physical activity, reduce pain and improve self-perceived performance and satisfaction. METHODS/DESIGN: This randomized, double-blinded, placebo-controlled, multicenter trial is conducted in a clinical setting involving three health regions in Norway. Ninety-six children with spastic CP, referred for single-level injections with BoNT-A in the calf muscles, will be invited to participate. Those who are enrolled will be randomized to receive either injections with BoNT-A (Botox®) or 0.9% saline in the calf muscles. Stratification according to age and study center will be made. The allocation ratio will be 1:1. Main inclusion criteria are (1) age 4 - 17.5 years, (2) Gross Motor Function Classification System levels I and II, (3) no BoNT-A injections in the lower limbs during the past 6 months and (4) no orthopedic surgery to the lower limbs during the past 2 years. The outcome measures will be made at baseline and 4, 12 (primary endpoint) and 24 weeks after injections. Primary outcome is change in energy cost during walking. Secondary outcomes are change in walking capacity, change in activity, perceived change in performance and satisfaction in mobility tasks, and pain. The primary analysis will use a linear mixed model to test for difference in change in the outcome measures between the groups. The study is approved by the Regional Ethical Committee and The Norwegian Medicines Agency. Recruitment started in September 2015. DISCUSSION: The evaluation of effect is comprehensive and includes objective standardized tests and measures on both impairment and activity level. Results are to be expected by spring 2019. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02546999 . Registered on 9 September 2015.

Treadmill Training or Progressive Strength Training to Improve Walking in People with Multiple Sclerosis? A Randomized Parallel Group Trial.

BACKGROUND AND PURPOSE: The most effective treatment approach to improve walking in people with multiple sclerosis (MS) is not known. The aim of this trial was to assess the efficacy of treadmill training and progressive strength training on walking in people with MS. METHODS: A single blinded randomized parallel group trial was carried out. Eligible participants were adults with MS with Expanded Disability Status Scale score ≤6. A total of 29 participants were randomized and 28 received the allocated exercise intervention, treadmill (n = 13) or strength training (n = 15). Both groups exercised 30 minutes, three times a week for 8 weeks. Primary outcome was The Functional Ambulation Profile evaluated by the GAITRite walkway. Secondary outcomes were walking work economy and balance control during walking, measured by a small lightweight accelerometer connected to the lower back. Testing was performed at baseline and the subsequent week after completion of training. RESULTS: Two participants were lost to follow-up, and 11 (treadmill) and 15 (strength training) were left for analysis. The treadmill group increased their Functional Ambulation Profile score significantly compared with the strength training group (p = .037). A significant improvement in walking work economy (p = .024) and a reduction of root mean square of vertical acceleration (p = .047) also favoured the treadmill group. DISCUSSION: The results indicate that task-specific training by treadmill walking is a favourable approach compared with strength training to improve walking in persons with mild and moderate MS. Implications for Physiotherapy practice, this study adds knowledge for the decision of optimal treatment approaches in people with MS. Copyright © 2015 John Wiley & Sons, Ltd.

Involuntary and voluntary muscle activation in children with unilateral cerebral palsy--relationship to upper limb activity.

BACKGROUND: Spasticity and reduced strength are both primary neuromuscular impairments associated with cerebral palsy (CP). However, it is unclear whether spasticity or reduced strength is the strongest contributor to activity limitations. AIM: To study whether involuntary activation of the biceps brachii muscle, in addition to reduced strength, contributes to limitations in upper limb activity in children with CP. METHOD: Fifteen children with unilateral CP (9 males and 6 females, age range 8-17 years) participated in this study. Involuntary activation, reflecting spasticity, was studied as biceps brachii activity during passive elbow extension at four isokinetic velocities (10, 90, 180 and 300°/s). Elbow flexion peak torque, reflecting strength, was measured during maximal voluntary isometric contraction, and concurrent biceps brachii activity was registered reflecting voluntary muscle activation. Bimanual upper limb activity was assessed in the performance domain using the Assisting Hand Assessment (AHA). RESULTS: Both involuntary and voluntary muscle activation were related to activity, the former negatively, but voluntary activation showed the strongest relationship (Spearmans rho = .84). Involuntary muscle activation at 10, 90 and 180°/s was negatively related to muscle strength (Spearmans rho = -.63, -.58 and -.62, respectively). CONCLUSIONS: Our results do not indicate that spasticity affects upper limb activity in addition to strength. Most likely, muscle weakness and spasticity jointly contribute to activity limitations, reflected by the strong relationship between the ability to voluntarily activate a muscle and activity performance.

The role of co-activation in strength and force modulation in the elbow of children with unilateral cerebral palsy.

To study the role of coactivation in strength and force modulation in the elbow joint of children and adolescents with cerebral palsy (CP), we investigated the affected and contralateral arm of 21 persons (age 8-18) with spastic unilateral CP in three tasks: maximal voluntary isokinetic concentric contraction and passive isokinetic movement during elbow flexion and extension, and sub-maximal isometric force tracing during elbow flexion. Elbow flexion-extension torque and surface electromyography (EMG) of the biceps brachii (BB) and triceps brachii (TB) muscles were recorded. During the maximal contractions, the affected arm was weaker, had decreased agonist and similar antagonist EMG amplitudes, and thus increased antagonist co-activation (% of maximal activity as agonist) during both elbow flexion and extension, with higher coactivation levels of the TB than the BB. During passive elbow extension, the BB of the affected arm showed increased resistance torque and indication of reflex, and thus spastic, activity. No difference between the two arms was found in the ability to modulate force, despite increased TB coactivation in the affected arm. The results indicate that coactivation plays a minor role in muscle weakness in CP, and does not limit force modulation. Moreover, spasticity seems particularly to increase coactivation in the muscle antagonistic to the spastic one, possibly in order to increase stability.