Pilot study of a virtual weight management program for Duchenne muscular dystrophy.

INTRODUCTION/AIMS: Young people with Duchenne muscular dystrophy (DMD) are at increased risk of obesity. Weight management is important to families; however, several barriers exist. This pilot study aimed to investigate the feasibility and acceptability of a co-designed weight management program for DMD. METHODS: The Supporting Nutrition and Optimizing Wellbeing Program (SNOW-P) was a single-arm diet and behavior weight management intervention delivered via weekly telehealth/phone visits over 6 weeks to young people with DMD and obesity (body mass index (BMI) ≥95th percentile) and their caregivers. Using an online survey, caregivers of boys with DMD were consulted on the structure and topics delivered in SNOW-P. Primary outcomes were feasibility and acceptability; secondary outcomes were weight, physical function, and quality of life at 6- and 12-weeks follow-up. RESULTS: Of nineteen eligible participants, eight were enrolled (median age 11.4 years, range 4.9-15.8), and seven completed the program. Visit attendance was high (88%-100%); most participants reported high satisfaction and that participation was easy. Suggested changes included online and visual DMD-specific resources. At 6-weeks, median change in weight z-scores was -0.01 (IQR: -0.23, 0.17) indicating that on average, weight gain tracked as expected for age. Waist circumference measured by caregivers lacked accuracy and the completion rate of caregiver-reported secondary outcome measures (e.g., food diaries) was low. DISCUSSION: A co-designed, telehealth/phone weight management program appeared to be feasible and acceptable in a small group of boys with DMD. An adapted, hybrid telehealth and face-to-face program is recommended for efficacy testing.

Exploring caregivers' attitudes and beliefs about nutrition and weight management for young people with Duchenne muscular dystrophy.

INTRODUCTION/AIMS: Obesity disproportionately affects children and adolescents with Duchenne muscular dystrophy (DMD) and with adverse consequences for disease progression. This study aims to: explore barriers, enablers, attitudes, and beliefs about nutrition and weight management; and to obtain caregiver preferences for the design of a weight management program for DMD. METHODS: We surveyed caregivers of young people with DMD from four Australian pediatric neuromuscular clinics. Survey questions were informed by the Theoretical Domains Framework and purposefully designed to explore barriers and enablers to food and weight management. Caregivers were asked to identify their preferred features in a weight management program for families living with DMD. RESULTS: Fifty-three caregivers completed the survey. Almost half (48%) perceived their son as above healthy weight. Consequences for those children were perceived to be self-consciousness (71%), a negative impact on self-esteem (64%) and movement (57%). Preventing weight gain was a common reason for providing healthy food and healthy eating was a high priority for families. Barriers to that intention included: time constraints, selective food preferences, and insufficient nutrition information. Caregivers preferred an intensive six-week weight management program addressing appetite management and screen time. DISCUSSION: Managing weight is an important issue for caregivers of sons with DMD; yet several barriers exist. Individualized 6 week programs are preferred by caregivers to improve weight management for DMD.

Clinical practice guideline for the management of paediatric Charcot-Marie-Tooth disease.

BACKGROUND AND OBJECTIVES: Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy and often presents during childhood. Guidelines for the optimal management of common problems experienced by individuals with CMT do not exist, for either children or adults. We formed the Paediatric CMT Best Practice Guidelines Consortium to develop evidence and consensus-based recommendations for the clinical management of children and adolescents with CMT, with the primary objective of promoting optimal, standardised care globally. METHODS: Development of this clinical practice guideline involved a series of systematic reviews covering 10 clinical questions, modified Delphi methodology involving an international panel of clinicians to generate consensus where evidence did not exist, and application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to evaluate the body of literature and formulate recommendations. RESULTS: The final guideline includes three evidence-based and 31 consensus-based recommendations. They encompass the management of muscle weakness, balance and mobility impairment, sensory symptoms, muscle cramps, impaired upper limb function, respiratory impairment, maintenance of joint range of motion and non-surgical management of joint deformity. Consensus was not achieved in some management areas, reflecting differences in practice between clinicians and healthcare settings, and highlighting the need for further research. CONCLUSIONS: This clinical practice guideline provides practical and implementable guidance on the management of common clinical problems experienced by children with CMT and advocates for improved access to multidisciplinary care. Successful dissemination and implementation of these recommendations will be critical in ensuring their application across multiple healthcare settings.

Delivering multidisciplinary neuromuscular care for children via telehealth.

INTRODUCTION/AIMS: In response to coronavirus disease 2019 (COVID-19) pandemic restrictions int 2020, our face-to-face (F2F) multidisciplinary neuromuscular clinic (NMC) transitioned to widespread use of telehealth (TH). This study aimed to (1) understand parent/guardian, child, and clinician perceptions of TH; (2) examine TH-related changes in clinical activity; and (3) use these findings to inform a future model of care for the NMC. METHODS: A clinical audit was undertaken to examine clinical activity throughout 2018-2020. Online surveys were distributed to clinicians and parents of children attending the NMC via TH in 2020. A working group of clinicians created a checklist to guide a future hybrid model of TH and F2F care. RESULTS: Total clinical activity in 2020 was maintained from previous years; 62.8% of all appointments occurred via TH, and 82.3% of patients attended NMC by TH at least once. Ninety-nine parents (30.6% response rate), 52 children, and 17 clinicians (77% response rate) responded to the survey. All groups reported better interaction when F2F compared to TH. Eighty percent of parents identified advantages of TH and reported lower levels of stress. A lack of "hands-on" physical assessment was identified by parents and clinicians as a TH limitation. Most families (68.1% of parents; 58.8% of children) and all clinicians indicated a preference for a mix of TH and F2F NMC appointments in the future. DISCUSSION: This study has informed a checklist to guide future TH use in a new hybrid model of care. Further investigation is required to assess health impacts of TH use in pediatric neuromuscular care.

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

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.

A phase 2 open-label study of the safety and efficacy of weekly dosing of ATL1102 in patients with non-ambulatory Duchenne muscular dystrophy and pharmacology in mdx mice.

BACKGROUND: ATL1102 is a 2'MOE gapmer antisense oligonucleotide to the CD49d alpha subunit of VLA-4, inhibiting expression of CD49d on lymphocytes, reducing survival, activation and migration to sites of inflammation. Children with DMD have dystrophin deficient muscles susceptible to contraction induced injury, which triggers the immune system, exacerbating muscle damage. CD49d is a biomarker of disease severity in DMD, with increased numbers of high CD49d expressing T cells correlating with more severe and progressive weakess, despite corticosteroid treatment. METHODS: This Phase 2 open label study assessed the safety, efficacy and pharmacokinetic profile of ATL1102 administered as 25 mg weekly by subcutaneous injection for 24 weeks in 9 non-ambulatory boys with DMD aged 10-18 years. The main objective was to assess safety and tolerability of ATL1102. Secondary objectives included the effect of ATL1102 on lymphocyte numbers in the blood, functional changes in upper limb function as assessed by Performance of Upper Limb test (PUL 2.0) and upper limb strength using MyoGrip and MyoPinch compared to baseline. RESULTS: Eight out of nine participants were on a stable dose of corticosteroids. ATL1102 was generally safe and well tolerated. No serious adverse events were reported. There were no participant withdrawals from the study. The most commonly reported adverse events were injection site erythema and skin discoloration. There was no statistically significant change in lymphocyte count from baseline to week 8, 12 or 24 of dosing however, the CD3+CD49d+ T lymphocytes were statistically significantly higher at week 28 compared to week 24, four weeks past the last dose (mean change 0.40x109/L 95%CI 0.05, 0.74; p = 0.030). Functional muscle strength, as measured by the PUL2.0, EK2 and Myoset grip and pinch measures, and MRI fat fraction of the forearm muscles were stable throughout the trial period. CONCLUSION: ATL1102, a novel antisense drug being developed for the treatment of inflammation that exacerbates muscle fibre damage in DMD, appears to be safe and well tolerated in non-ambulant boys with DMD. The apparent stabilisation observed on multiple muscle disease progression parameters assessed over the study duration support the continued development of ATL1102 for the treatment of DMD. TRIAL REGISTRATION: Clinical Trial Registration. Australian New Zealand Clinical Trials Registry Number: ACTRN12618000970246.

Correlation between whole body muscle MRI and functional measures in paediatric patients with facioscapulohumeral muscular dystrophy.

Symptoms and severity of facioscapulohumeral muscular dystrophy (FSHD) can vary greatly, even within the same family. Clinical trial readiness requires accurate and reliable methods of assessing disease stage and progression. MRI has not previously been assessed as a disease biomarker in paediatric FSHD. Eleven patients with FSHD1 underwent whole body muscle MRI. Pre-selected muscles were analysed by a paediatric radiologist using the semi-quantitative Mercuri/Kim method. Within each domain (oedema, fat replacement, atrophy) scores for each muscle were then summated to give each participant three cumulative domain scores. The same participants had functional measures scored: FSHD-CSS (Ricci), FSHD-CS (Lamperti), FSHD-COM, PUL2.0, MFM-32, 6MWT, myometry and manual muscle testing. Pearson coefficient was calculated to determine strength of correlation. The scores for atrophy and fat replacement showed strong correlation with functional outcome measures, particularly FSHD-CSS, FSHD-CS and FSHD-COM. In contrast, muscle oedema correlated poorly with all functional outcome measures, with no relationship seen to the 6MWT. This study of eleven children suggests that semi-quantitative visual Mercuri score utilising fat replacement or atrophy on whole body muscle MRI correlates strongly with disease-specific functional measures and may be a useful measure of disease severity in paediatric FSHD.

Characterising gait in paediatric neuromuscular disorders: an observational study of spatio-temporal gait in a clinical cohort.

AIM: Few studies have characterised the relationship between disease and gait function in children and young people with rare neuromuscular disorders (NMDs). This study aimed to describe the relationship between disease and gait in a large paediatric cohort from a neuromuscular outpatient clinic. METHODS: A prospective, cross-sectional study of gait in independently ambulant children and young people aged 4-21 years with a clinical or genetically confirmed NMD. Participants traversed an electronic walkway barefoot and in footwear at self-selected and fast pace. Analysis of disease included a typically developing (TD) reference group. RESULTS: A sample of 113 participants with NMD, mean age 9.5 years (SD 3.1), 28% female, grouped into nine diagnostic subgroups. Eighty percent reported limitations to functional mobility. Children with NMD walked slower, with a shorter and wider step compared to a TD reference group, with moderate to large effect sizes for each of these gait parameters indicative of the clinical significance of these gait deviations. Children with Duchenne muscular dystrophy (DMD) walked slowest with a markedly wide gait pattern. Footwear had little overall effect on gait in children with NMDs. All children could accelerate over short distances. CONCLUSIONS: Gait, notably speed, step length, and width are clinically significant biomarkers of disease in paediatric NMDs, affording objective functional measures in clinical settings and research.Implications for rehabilitationGait should be considered a functional biomarker of disease in children and young people with neuromuscular disorders (NMDs).Comparison of gait in a paediatric neuromuscular cohort indicates that children with Duchenne muscular dystrophy (DMD) walk slowest with a shorter step length and a wider step width which increases with age and disease progression.Measurement of gait speed is a simple, pragmatic tool to monitor disease progression in the outpatient clinical environment and relates to everyday function.In clinical research, gait can be measured as a functional outcome to demonstrate change from disease-modifying interventions and treatments in NMDs.

The effects of calf massage in boys with Duchenne muscular dystrophy: a prospective interventional study.

PURPOSE: We explored the effects of standardized calf massage in ambulant boys with Duchenne muscular dystrophy (DMD) using a prospective study design. MATERIALS AND METHODS: Twenty boys completed two study visits, 1 week apart. At both visits, each leg received a 10-min calf massage (intervention) and a 10-min control rest period (placebo) in randomized order. Muscle length of calf and hamstrings and gastrocnemius stiffness were measured by a blinded assessor before and after intervention and placebo. Measures of gait function (timed 10-m walk/run and spatio-temporal gait parameters); gastrocnemius muscle ultrasound findings; participant perception of leg pain, stiffness and effort of walking and general psychological well-being were also collected. RESULTS: Consistent significant small increases in muscle length of soleus, gastrocnemius and hamstrings were recorded post-massage, and gastrocnemius stiffness decreased. Small changes in gastrocnemius and soleus length only were also recorded following the control rest period. Gait function and general well-being remained stable throughout. Measurement across both study visits suggested that gains in muscle length may be cumulative with repeated massage. CONCLUSIONS: Calf massage is safe and associated with benefits to muscle length and stiffness for ambulant boys with DMD.Implications for RehabilitationIn a small sample of boys with Duchenne muscular dystrophy, calf massage was found to be safe, well-tolerated and associated with increased muscle length and decreased stiffness.The use of massage may assist in managing muscle length in boys with Duchenne muscular dystrophy.

Clinimetric properties of the alberta infant motor scale in infants born preterm.

PURPOSE: The Alberta Infant Motor Scale (AIMS) is a standardized motor assessment for young infants. This study aimed to examine the reliability of the AIMS in a group of infants born at or before 29 weeks of gestation. METHODS: Fifty-nine infants born preterm were recruited. Two experienced pediatric physical therapists participated in this reliability study. Infants were assessed at 4, 8, 12, and 18 months corrected age (CA). RESULTS: Intrarater reliability was high (intraclass correlation coefficient [ICC] > or =0.99). The ICC for interrater reliability varied from 0.85 to 0.97. The ICC was low at 4 and 18 months CA. CONCLUSIONS: The AIMS is reliable in evaluating motor development in infants born preterm. Clinicians should be cautious about using the AIMS in infants at very young ages and those approaching independent ambulation. Accurate placement of the window on a movement repertoire is crucial. Attention is required when using the AIMS in infants developing atypically.

Dejerine-Sottas disease in childhood-Genetic and sonographic heterogeneity.

Introduction: The nerve sonographic features of Dejerine-Sottas disease (DSD) have not previously been described. Methods: This exploratory cross-sectional, matched, case-control study investigated differences in nerve cross-sectional area (CSA) in children with DSD compared to healthy controls and children with Charcot-Marie-Tooth disease type 1A (CMT1A). CSA of the median, ulnar, tibial, and sural nerves was measured by peripheral nerve ultrasound. The mean difference in CSA between children with DSD, controls, and CMT1A was determined individually and within each group. Results: Five children with DSD and five age- and sex-matched controls were enrolled. Data from five age-matched children with CMT1A was also included. Group comparison showed no mean difference in nerve CSA between children with DSD and controls. Individual analysis of each DSD patient with their matched control indicated an increase in nerve CSA in three of the five children. The largest increase was observed in a child with a heterozygous PMP22 point mutation (nerve CSA fivefold larger than a control and twofold larger than a child with CMT1A). Nerve CSA was moderately increased in two children-one with a heterozygous mutation in MPZ and the other of unknown genetic etiology. Conclusions: Changes in nerve CSA on ultrasonography in children with DSD differ according to the underlying genetic etiology, confirming the variation in underlying pathobiologic processes and downstream morphological abnormalities of DSD subtypes. Nerve ultrasound may assist in the clinical phenotyping of DSD and act as an adjunct to known distinctive clinical and neurophysiologic findings of DSD subtypes. Larger studies in DSD cohorts are required to confirm these findings.

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.

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.