Kate Carroll

Peripheral nerve ultrasound in pediatric Charcot-Marie-Tooth disease type 1A

Objective: To investigate differences in nerve cross-sectional area (CSA) as measured by peripheral nerve ultrasound in children with Charcot-Marie-Tooth disease type 1A (CMT1A) compared to healthy controls. Methods: This was a cross-sectional, matched, case-control study. CSA of the median, ulnar, tibial, and sural nerves was measured by peripheral nerve ultrasound. The mean difference in CSA between children with CMT1A and controls at each nerve site was determined. The relationship between nerve CSA and age/body metrics, and between nerve CSA and neurologic disability in CMT1A, was also evaluated. Results: Twenty-nine children with CMT1A and 29 age- and sex-matched controls were enrolled. Nerve CSA was significantly increased in children with CMT1A compared to controls (1.9- to 3.5-fold increase, p < 0.001). The increase in nerve CSA with age was disproportionately greater in those with CMT1A. Nerve CSA showed a strong positive linear correlation with age, height, and weight in both the CMT1A and control groups. Disease severity correlated with both nerve CSA and age. Conclusions: Children with CMT1A have significantly increased nerve CSA compared to controls, and the increase in nerve CSA with age is disproportionately greater in CMT1A, suggesting ongoing nerve hypertrophy throughout childhood. Nerve CSA correlates with neurologic disability. These findings demonstrate the utility of peripheral nerve ultrasound as a diagnostic tool in pediatric neuropathies, and as an outcome measure in natural history studies and clinical trials in CMT1A. Classification of evidence: This study provides Class IV evidence that measurement of nerve CSA by peripheral nerve ultrasound accurately identifies patients with CMT1A.

Gait in children and adolescents with Charcot-Marie-Tooth disease: a systematic review.

Symptoms of Charcot‐Marie‐Tooth (CMT) disease typically arise in childhood or adolescence with gait difficulty most common. A systematic review was conducted to synthesise, review, and characterise gait in paediatric CMT. Health‐related electronic databases were reviewed with search terms related to CMT and gait. Of 454 articles, 10 articles describing seven studies met eligibility criteria; samples ranged from 1 to 81, included mixed CMT sub‐types and had a participant mean age of 13 years. Assessments included a variety of methods to examine only barefoot gait. Heterogeneity of gait patterns was noted. Children and adolescents with CMT walked slower, most likely due to shorter stride length. Common kinematic and kinetic abnormalities included significant foot drop during swing, reduced calf muscle power, and proximal compensatory mechanisms in the lower limb. Little data were found to inform typical functional gait characteristics or change over time. Of note, barefoot assessment does not reflect function in everyday life where footwear is commonly worn. With limited existing literature, future studies of gait in paediatric CMT need to evaluate the influence of diagnostic sub‐types and disease progression; the effect of factors such as footwear and the environment; and to explore changes in gait and function throughout childhood and adolescence.

A multinational study on motor function in early-onset FSHD

Objectives To investigate motor function associations with age, sex, and D4Z4 repeats among participants with early-onset facioscapulohumeral muscular dystrophy (FSHD) type 1 as defined by weakness onset before 10 years of age. Methods We collected standardized motor assessments, including manual muscle testing (MMT), quantitative muscle testing, functional motor evaluations, and clinical severity scores (CSSs), at 12 Cooperative International Neuromuscular Research Group centers. To measure associations, we used linear regression models adjusted for sex, evaluation age, age at onset of weakness, and D4Z4 repeats. Results Among 52 participants (60% female, mean age 22.9 ± 14.7 years), weakness was most pronounced in the shoulder and abdominal musculature. Older enrollment age was associated with greater CSSs (p = 0.003). When adjusted for enrollment age, sex, and D4Z4 repeats, younger age at onset of facial weakness was associated with greater CSSs, slower velocities in timed function tests, and lower MMT scores (p < 0.05). Conclusion Significant clinical variability was observed in early-onset FSHD. Earlier age at onset of facial weakness was associated with greater disease severity. Longitudinal assessments are needed to determine the rate of disease progression in this population.

Physical activity and the use of standard and complementary therapies in Duchenne and Becker muscular dystrophies

PURPOSE To record the use and perceived benefits of mainstream allied health services, complementary therapies, nutritional supplements and structured physical activity in a paediatric population of males with Duchenne or Becker muscular dystrophy. METHOD A questionnaire was distributed to 125 parents of males with a dystrophinopathy within a tertiary neuromuscular clinic population in Melbourne, Australia. RESULTS Response rate to the survey was 41%. Most families (73%) reported use of allied health services: physiotherapy (65%), occupational therapy (47%), and psychology (25%). The most commonly used complementary therapy was massage (31%). Sixty-five percent of families reported using nutritional supplements. Fifty-one and 38% of families reported participation in swimming and other organised sports, respectively. Physical and psychological benefits of sporting activities were identified by families. Participation in physical activity was lowest in those transitioning to full-time wheelchair use. CONCLUSIONS Access to allied health services by boys with dystrophinopathies is variable and inconsistent with published international standards of care. There is frequent use of complementary therapies, despite a lack of proven efficacy. Studies of the effects of such therapies would support provision of evidence-based advice to families. Continued involvement in physical activity for those boys with declining function should be supported by clinicians.

Evaluation of Serial Casting for Boys with Duchenne Muscular Dystrophy: A Case Report

ABSTRACT Aim: To report the effects of below-knee serial casting in two boys with Duchenne muscular dystrophy who presented with well-preserved strength and calf shortening. Methods: Bilateral below-knee serial casts were applied over two weeks with follow-up of daily stretching and wearing of customized night splints. Outcome measures were performed at baseline, 1, 3, 6, and 12 months post-casting. These included measures of calf length, leg strength, motor function, endurance, and spatio-temporal gait parameters. Results: Both boys completed serial casting with gains in muscle length. No adverse effects on strength or motor function were observed over a 12-month follow-up period.

Gait and footwear in children and adolescents with Charcot-Marie-Tooth disease: A cross-sectional, case-controlled study

OBJECTIVE Children with Charcot-Marie-Tooth disease (CMT) report problems with gait and footwear. We evaluated differences in spatio-temporal gait variables and gait variability between children with CMT and typically developing (TD) children, and investigated the effect of footwear upon gait. METHOD A cross-sectional study of 30 children with CMT and 30 age- and gender-matched TD children aged 4-18 years. Gait was assessed at self-selected speed on an electronic walkway while barefoot and in two types of the childs own footwear; optimal (e.g., athletic-type runners) and suboptimal (e.g., flip-flops). RESULTS Children with CMT walked more slowly (mean (SD) -13.81 (3.61) cm/s), with shorter steps (-6.28 (1.37) cm), wider base of support (+2.47 (0.66) cm; all p < 0.001) and greater base of support variability (0.48 (0.15) cm, p = 0.002) compared to TD children. Gait was faster in optimal footwear than suboptimal (-7.55 (1.31) cm/s) and barefoot (-7.42 (1.07) cm/sec; both p < 0.001) in the combined group of children. Gait in suboptimal footwear was more variable compared to barefoot and optimal footwear. Greater base of support variability and reduced balance was moderately correlated for both groups (CMT and TD). CONCLUSION Gait is slower with shorter, wider steps and greater base of support variability in children with CMT. Poor balance is associated with greater base of support gait variability. Suboptimal footwear negatively affects gait in all children (CMT and TD), which has clinical implications for children and adolescents with CMT who have weaker feet and ankles, and poor balance.

Dejerine-Sottas disease in childhood-Genetic and sonographic heterogeneity

The nerve sonographic features of Dejerine‐Sottas disease (DSD) have not previously been described.

Falls in paediatric Charcot-Marie-Tooth disease: a 6-month prospective cohort study

Objective To prospectively study falls in children and adolescents with Charcot-Marie-Tooth disease (CMT). Design Prospective cohort study. Setting Neuromuscular outpatient clinic of a tertiary paediatric hospital. Patients Sixty children and adolescents (‘children’) aged 4–18 years, 30 with CMT and 30 typically developing (TD). Main outcome measures Falls rate over 6 months and falls characteristics questionnaire. Results Twenty-two children with CMT reported falling at least once in 6 months compared with eight TD children (CMT 2819 (0–1915), TD 31 (0–6) total falls (range)). Detailed falls characteristics were collected from 242 individual falls (CMT 216, TD 26). Injurious falls were reported by 19 children with CMT (74 falls) compared with 2 TD children (3 falls), with cuts, grazes and bruising most common. No fractures were sustained and no child required hospitalisation. However, 12 injuries from falls in children with CMT required management by a healthcare provider, versus none in TD children. Tripping was the most common mechanism of falls in both groups. Age was the strongest predictor of falls (ρ=−0.53, p=0.006) with all children (CMT and TD) aged <7 years falling. Balance was the strongest impairment-related predictor of falls (ρ=−0.47, p=0.02). The conservative estimate of risk of falls in children and adolescents with CMT was 33 times higher than their TD peers (incidence rate ratio=32.8, 95% CI 10.2 to 106.0). Conclusions Children and adolescents with CMT fall more often than TD peers and sustain more injuries when they fall.

Deterioration in gait and functional ambulation in children and adolescents with Charcot–Marie–Tooth disease over 12 months

Children and adolescents with Charcot-Marie-Tooth disease (CMT) report problems with gait. Little is known about gait changes over time in children with this degenerative disease. This prospective longitudinal study investigated change in spatio-temporal gait parameters and functional ambulation. Two assessments were conducted 12 months apart. Assessments included: barefoot gait on an electronic walkway; functional ambulation with a six minute walk test and the Functional Mobility Scale; and disease severity with the CMT Pediatric Scale. Gait and strength data were normalised to body anthropometrics. Twenty-seven children (mean age 12.2, SD 3.7 years) with various CMT subtypes (CMT1A 52%) were evaluated. Over 12 months, normalised variables of gait speed, stride length and six minute walk distance significantly decreased. The CMT Pediatric Scale increased 0.7 points, indicating marginal but not significant worsening of disease; notably calf strength decreased significantly over 12 months. Baseline maximum ankle dorsiflexion angle, gastrocnemius and hamstrings length, and calf strength correlated with decline in gait speed, with maximum ankle dorsiflexion angle as the strongest predictor. Deterioration over one year in normalised variables of gait speed, stride length and distance walked in six minutes are indicators of functional decline and disease progression in children and adolescents with CMT.

S.P.51 A study of below knee serial casting for calf contracture in ambulant boys with Duchenne muscular dystrophy

Abstract The progressive muscle weakness that occurs in Duchenne muscular dystrophy (DMD) is known to be associated with secondary muscle tightness and contracture. The Achilles tendon (TA) and calf muscle complex (gastrocnemius and soleus) is typically one of the earliest and most severely affected muscle groups. It has been noticed clinically that there is a subset of boys who develop surprisingly early shortening in the presence of well-preserved lower limb muscle strength. A small prospective study has commenced to assess the effects of short term below knee serial casting on muscle length as well as strength, physical function and endurance. Tight inclusion criteria ensure that only boys with good anti-gravity muscle strength and range of motion at hip and knee are included. Outcome measures include goniometry, myometry, timed function tests, the North Star Ambulatory Assessment, Six Minute Walk Test, falls frequency and measurement of gait parameters using the GAITRite system. Early data will be presented.