L-carnitine supplementation for muscle weakness and fatigue in children with neurofibromatosis type 1: A Phase 2a clinical trial.

Reduced muscle tone, muscle weakness, and physical fatigue can impact considerably on quality of life for children with neurofibromatosis type 1 (NF1). Human muscle biopsies and mouse models of NF1 deficiency in muscle show intramyocellular lipid accumulation, and preclinical data have indicated that L-carnitine supplementation can ameliorate this phenotype. The aim of this study is to examine whether daily L-carnitine supplementation is safe and feasible, and will improve muscle strength and reduce fatigue in children with NF1. A 12-week Phase 2a trial was conducted using 1000 mg daily oral levocarnitine tartrate supplementation. Recruited children were between 8 and 12 years old with a clinical diagnosis of NF1, history of muscle weakness and fatigue, and naïve to L-carnitine. Primary outcomes were safety (self-reporting, biochemical testing) and compliance. Secondary outcomes included plasma acylcarnitine profiles, functional measures (muscle strength, long jump, handwriting speed, 6-minute-walk test [6MWT]), and parent-reported questionnaires (PedsQL™, CBCL/6-18). Six children completed the trial with no self-reported adverse events. Biochemical tests for kidney and liver function were normal, and the average compliance was 95%. Plasma acylcarnitine levels were low, but within a range not clinically linked to carnitine deficiency. For strength measures, there was a mean 53% increase in dorsiflexion strength (95% confidence interval [CI] 8.89-60.75; p = 0.02) and mean 66% increase in plantarflexion strength (95% CI 12.99-134.1; p = 0.03). In terms of muscle performance, there was a mean 10% increase in long jump distance (95% CI 2.97-16.03; p = 0.01) and 6MWT distance (95% CI 5.88-75.45; p = 0.03). Comparison with the 1000 Norms Project data showed a significant improvement in Z-score for all of these measures. Parent reports showed no negative impact on quality of life, and the perceived benefits led to the majority of individuals remaining on L-carnitine after the study. Twelve weeks of L-carnitine supplementation is safe and feasible in children with NF1, and a Phase 3 trial should confirm the efficacy of treatment.

Replicating and redesigning ankle-foot orthoses with 3D printing for children with Charcot-Marie-Tooth disease.

BACKGROUND: Children with the most common inherited neuropathy, Charcot-Marie-Tooth disease (CMT), are often prescribed ankle-foot orthoses (AFOs) to improve walking ability and prevent falls by reducing foot drop, postural instability, and other gait impairments. These externally worn assistive devices are traditionally custom-made using thermoplastic vacuum forming. This labour-intensive manufacturing process often results in AFOs which are cumbersome due to limited design options, and are associated with low acceptability, discomfort, and suboptimal impact on gait. The aim of this study was to determine how 3D printing can be used to replicate and redesign AFOs in children with CMT. METHODS: Traditional AFOs, 3D printed replica AFOs (same design as traditional AFOs), 3D printed redesigned AFOs and a shoes only control condition were compared in 12 children with CMT. 3D printed AFOs were manufactured using material extrusion in Nylon-12. 3D gait analysis (temporal-spatial, kinematic, kinetic), in-shoe pedobarography and self-reported satisfaction were used to compare conditions. The primary kinematic and kinetic outcome measures were maximum ankle dorsiflexion in swing and maximum ankle dorsiflexor moment in loading response, to capture foot drop and an absent of heel rocker. RESULTS: The 3D printed replica AFOs were comparable to traditional AFOs for all outcomes. The 3D printed replica AFOs improved foot position at initial contact and during loading response and significantly reduced pressure beneath the whole foot, rearfoot and forefoot compared to the shoes only. The 3D printed redesigned AFOs produced a device that was significantly lighter (mean -35.2, SD 13.3%), and normalised maximum ankle dorsiflexor moment in loading response compared to shoes only and traditional AFOs. SIGNIFICANCE: 3D printing can be used to replicate traditional handmade AFOs and to redesign AFOs to produce a lighter device with improved biomechanics by incorporating novel design features.

The impact of being overweight on the mobility, temporal-spatial and kinematic aspects of gait in children with cerebral palsy.

AIM: Obesity causes altered gait patterns in typically developing children, but its effect on gait in children with physical disabilities is largely unknown. This study explores associations between body mass index (BMI), functional mobility and gait in children with cerebral palsy (CP). METHOD: An observational cross-sectional study was conducted using three-dimensional gait analysis data from 197 children with CP, Gross Motor Functional Classification System (GMFCS) levels I to III. BMI values were categorised using the Centres for Disease Control and Prevention (2000) BMI percentiles, which are specific to age and gender. Regression analyses, with GMFCS level as a covariate, explored associations between BMI category and temporal-spatial, kinematic and functional mobility variables. Analyses included children categorised as healthy weight and overweight/obese only (n = 174), with underweight children excluded (n = 23). RESULTS: 131 children (mean age 10.5 years, SD 3) were categorised as healthy weight and 43 children (mean age 9.6 years, SD 2.5) as overweight or obese. BMI was not associated with most gait variables. Increased double support time, reduced hip extension and increased ankle dorsiflexion were observed in children that were overweight, but most differences were small and of uncertain clinical significance. A lower proportion of overweight children walked independently over 500 m. CONCLUSION: We found little evidence that BMI has a substantial influence on gait patterns in children with CP but some to suggest it may affect long-distance mobility. Different research strategies are required to improve understanding of relationships between adiposity, strength and function, for effective targeting of interventions to improve mobility.

Can pedobarography predict the occurrence of heel rocker in children with lower limb spasticity?

BACKGROUND: Pedobarography software calculates the centre-of-pressure trajectory in relation to the foot to quantify foot contact patterns. This study presents two new pedobarography measures using the centre-of-pressure trajectory to assess heel rocker. METHODS: To validate these pedobarography measures against 3D gait analysis, emed®-x and Vicon Nexus gait analysis data were captured from 25 children aged 8-16 years (11 male) with unilateral (n = 18) and bilateral (n = 7) cerebral palsy or acquired brain injury. 3D gait analysis identified whether heel rocker was intact (n = 22 feet) or absent (n = 28 feet) based on centre-of-pressure at initial contact and the ankle kinematic curve between 0 and 2% of the gait cycle. Pedobarography measures calculated from the initial centre-of-pressure point were the distance to the heel (point of initial contact) and to the most posterior point of the trajectory (rollback), reported as a percentage of foot length. FINDINGS: The median point of initial contact in limbs with an intact heel rocker was 9% (range 7-12%) and median rollback was 0% (range 0-0.2%), whereas the median point of initial contact in limbs with an absent heel rocker was 58% (range 8-78%) and rollback was 18% (range 0-40%). Point of initial contact is the more accurate method for predicting heel rocker, with a threshold of 14% of foot length identifying the correct heel rocker status in 94% of cases. INTERPRETATION: Point of initial contact can assess heel rocker with high accuracy. Both point of initial contact and rollback provide sensitive information on foot strike pattern, enhancing the utility of pedobarography.

Surgical outcomes of cavovarus foot deformity in children with Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) causes disabling cavovarus foot deformity. Orthopaedic surgery is performed in severe cases; however few studies have investigated whether surgery improves health outcomes during childhood. This study investigated the impact of cavovarus surgery on validated physical, functional, parent/self-reported and biomechanical measures in 21 consecutive patients (mean age at surgery 12.5 years, SD 2.7) evaluated before and after surgery (mean duration 15.7 months, SD 5.9), and compared to natural history data from 206 children with CMT. Measures from the CMT Pediatric Scale evaluated foot alignment (Foot Posture Index), ankle flexibility (lunge test), strength (foot dorsiflexion/plantarflexion by hand-held dynamometry), function (balance, long jump, 6-minute walk test) and self-reported symptoms. Quality of life (Child Health Questionnaire) and gait (pressure loading) were also assessed. Foot Posture Index and lunge improved with surgery by 6.0 points (SD 3.2) and 6.1° (SD 7.3) respectively (p< 0.01), and differed to the natural course of the disease (p< 0.005). Self-reported daily trips/falls reduced from 60% to 13% (p = 0.016). Pressure improved beneath the rearfoot and midfoot (p = 0.043). Surgery had no effect on strength, function or quality of life, which generally mirrored the natural course. Cavovarus surgery improved foot alignment, ankle flexibility and self-reported trips/falls in children with CMT.

Impact of multilevel joint contractures of the hips, knees and ankles on the Gait Profile score in children with cerebral palsy.

BACKGROUND: Children with cerebral palsy are at risk of developing muscle contractures, often contributing to pain, structural deformities and mobility limitations. With the increasing use of gait indices to summarise the findings of three dimensional gait analysis (3DGA), the purpose of this study is to determine whether there is a relationship between multilevel joint contractures and the Gait Profile Score in children with cerebral palsy. METHODS: The Gait Profile Score, calculated from 3D gait analysis, and passive range of motion, strength and spasticity of the hips, knees and ankles in the sagittal plane were measured in 145 children with cerebral palsy (mean age:11 years,4 months; SD:2 years,10 months) (83 males) enrolled in the NSW Paediatric Gait Analysis Service Research Registry from 2011 to 2016. The relationships between these physical measures and the Gait Profile Score were explored using bivariate and multivariate correlations. FINDINGS: Reduced hip extension, knee extension and ankle dorsiflexion (knee extended) range of motion were correlated with a higher (worse) Gait Profile Score (r = -0.348 to -0.466, p < .001). Children with all joints contracted had a significantly higher Gait Profile Score (mean 17.5°, SD 6.2°) than those with no contractures (mean 11.0°, SD 2.3°) or ankle contractures only (mean 12.8°, SD 5.1°) (p < .05). Knee flexion weakness, reduced hip extension and ankle dorsiflexion (knee extended) range of motion predicted 47% of the Gait Profile Score. INTERPRETATION: The Gait Profile Score is a sensitive measure for demonstrating the relationship between multilevel sagittal plane joint contractures and kinematic gait. Clinically, this supports the use of the Gait Profile Score as a simplified measure to understand the contribution of contractures to functional gait limitations. Monitoring knee flexion strength, and hip extension and ankle dorsiflexion (knee extended) range of motion may assist clinicians in prioritising interventions to improve gait in this population.

How does rectus femoris fibrosis affect gait?

We report on a female patient with stiff-knee gait resulting from rectus femoris fibrosis, following multiple injections into the quadriceps musculature. Treatment planning and outcome were aided by instrumented three-dimensional gait analysis. One year after surgery, improvements were found in walking speed, step length, anterior pelvic tilt, knee flexion in swing, and ankle dorsiflexion in swing. Instrumented three-dimensional gait analysis was a useful tool for characterizing gait impairments and detecting changes after surgical intervention. Intramuscular injections into the rectus femoris muscle should be avoided to prevent stiff-knee gait and associated disability.

Inter-rater reliability of physiotherapists using the Pirani scoring system for clubfoot: comparison with a modified five-point scale.

This study examines inter-rater reliability between physiotherapists using the Pirani scoring system for clubfoot, and whether the addition of two scale points to give a modified five-point severity scale improves reliability. A total of 65 infant feet were assessed by two raters, with 21 different rater combinations used. The Pirani scoring system was found to be a reliable assessment tool when used by physiotherapists to score clubfoot, with a minimum of fair to good inter-rater reliability demonstrated across all clinical signs. The modified five-point scale proved significantly more reliable than the three-point scale; however, the benefit is not sufficient to warrant varying the original three-point scale.

Normative reference values for lower limb joint range, bone torsion, and alignment in children aged 4-16 years.

Normative reference values are essential to identify deviation from normal and evaluate response to treatment. As joint range of motion datasets specific to the pediatric population are infrequently reported in the literature, we determined lower limb passive joint range of motion and bone torsion values from 53 typically developing children aged 4-16 years. Our reference values were consistent with previously published norms, although for some measures, large variability in the literature exists. A clear correlation between joint range and age was observed in most measures. Our results highlight the importance of applying age-matched norms when attempting to identify deviation from normal in the growing child.