Merel Jansen

Quantitative muscle ultrasound is a promising longitudinal follow-up tool in Duchenne muscular dystrophy.

Responsive outcome measures are needed to follow the disease status of Duchenne muscular dystrophy (DMD) patients, as new therapeutic approaches become available for affected boys. Quantitative muscle ultrasound (QMUS) is potentially an attractive follow up tool for DMD because it reflects the severity of the dystrophic process without the need for invasive procedures, by quantifying echo intensity (i.e., mean grey level of muscle images) and muscle thickness. We performed a longitudinal follow-up of lower and upper extremity QMUS in 18 DMD patients and compared this with physical functioning in 11 of these patients. QMUS could be performed in every patient, and no patient was subjected to more than a total of 20min of ultrasound scanning time for this study. As expected we found a significant increase of echo intensity with age, reflecting increasing dystrophic muscle changes. This increase was related to ambulatory status, functional grading, muscle strength and motor ability. Our study establishes QMUS as a practical and child-friendly tool for the longitudinal follow up of DMD patients.

Assisted bicycle training delays functional deterioration in boys with Duchenne muscular dystrophy: the randomized controlled trial "no use is disuse".

Background. Physical training might delay the functional deterioration caused by disuse in boys with Duchenne muscular dystrophy (DMD). The “No Use Is Disuse” study is the first explorative, randomized controlled trial in boys with DMD to examine whether assisted bicycle training is feasible, safe, and beneficial. Methods. Ambulatory and recently wheelchair-dependent boys with DMD were allocated to the intervention or control group. The intervention group received assisted bicycle training of the legs and arms during 24 weeks. The control group received the same training after a waiting period of 24 weeks. The primary study outcomes were the Motor Function Measure (MFM) and the Assisted 6-Minute Cycling Test (A6MCT). Group differences were examined by an analysis of covariance. Results. Thirty boys (mean age 10.5 ± 2.6 years, 18 ambulant and 12 wheelchair-dependent) were allocated to the intervention (n = 17) or the control (n = 13) group. All boys in the intervention group (except one) completed the training. After 24 weeks, the total MFM score remained stable in the intervention group, whereas it had significantly decreased in the control group (Δ = 4.9, 95% confidence interval = 2.2-7.6). No significant group differences were found for the A6MCT. No serious adverse events were observed. Conclusions. Our results suggest that assisted bicycle training of the legs and arms is feasible and safe for both ambulant and wheelchair-dependent children and may decline the deterioration due to disuse. Progressive deterioration, however, may compromise the design of trials for DMD.

Health-Related Quality of Life and Its Relation to Disease Severity in Boys With Duchenne Muscular Dystrophy Satisfied Boys, Worrying Parents—A Case-Control Study

The progression of Duchenne muscular dystrophy is expected to negatively influence the patients’ health-related quality of life, but knowledge of the relationship with disease severity is limited. We investigated the relationship between health-related quality of life (KIDSCREEN-52 questionnaire) and disease severity (clinical assessments of body functions and activities) in 40 boys with Duchenne muscular dystrophy (19 ambulant, 21 wheelchair dependent) who were in different phases of the disease and underwent life-limiting events such as the loss of the ability to ambulate and the ability to lift the arms. In addition, we compared boys’ health-related quality of life perceptions with that of their parents. The participants’ health-related quality of life was similar to healthy peers’ and not influenced by disease severity, except for the physical domain. Parents scored much lower than the boys on the KIDSCREEN-52 domains Self Perception, Moods and Emotions, and Bullying. The latter finding needs attention in the management of Duchenne muscular dystrophy.

Quantitative muscle ultrasound and muscle force in healthy children: A 4-year follow-up study

No longitudinal data on the normal development of muscle thickness (MT), quantitative muscle ultrasound echo intensity (EI), and muscle force (MF) in healthy children are yet available.

Towards the harmonization of outcome measures in children with mitochondrial disorders

A clinical trial is only as reliable as its outcomes, therefore the careful and systematic selection of outcome measures is extremely important. Currently, the selection of outcome measures for clinical trials designed to evaluate new drugs in patients with mitochondrial disorders is inefficient and has not been addressed systematically. Given that meaningful data can be obtained only from trials in which outcomes are assessed using valid instruments, one should first focus on the validation of a set of selected instruments in the target population. The aim of this review is to systematically select a ‘toolbox’ of robust outcome measures that are relevant to all patients.

The assisted 6-minute cycling test to assess endurance in children with a neuromuscular disorder

Introduction: For late‐ or non‐ambulant children with a neuromuscular disorder no suitable endurance tests are currently available. We developed the assisted 6‐minute cycling test (A6MCT) for the legs and arms and investigated its psychometric properties in healthy boys and boys with Duchenne muscular dystrophy (DMD). Methods: Ninety‐nine healthy boys and 30 boys with DMD (12 wheelchair‐dependent) performed the A6MCT. Seventy healthy boys also performed the 6‐minute walk test (6MWT), and 23 boys performed the A6MCT twice within 2 weeks. Boys with DMD also performed the Motor Function Measure (MFM). Results: The A6MCT was feasible for >90% of all boys. Boys with DMD achieved fewer cycling revolutions than controls. The A6MCT was positively correlated with the 6MWT and was reproducible in healthy boys, and it correlated with disease severity in boys with DMD. Conclusions: The A6MCT is a promising outcome measure for the follow‐up of non‐ambulant children with a neuromuscular disorder. Muscle Nerve 46: 520–530, 2012

Upper Limb Training with Dynamic Arm Support in Boys with Duchenne Muscular Dystrophy: A Feasibility Study

Patients with Duchenne Muscular Dystrophy (DMD) develop progressive loss of arm function. Regular moderate-intensity activities are recommended to prevent disuse atrophy, but conventional resistance exercises are often too strenuous. We conducted a feasibility study to investigate the feasibility and safety of upper limb training with dynamic arm support. Eight boys with DMD who were unable to lift their arms against gravity (age 12-20 years) performed reaching movements with their non-dominant arm for 24 weeks. Participants played a virtual reality computer game and performed activities of daily living while using dynamic arm support. The dominant (untrained) arm of each participant served as a reference. Six of the eight participants completed the entire training program without any adverse events. The trained arm retained more motor function than the untrained arm in 4/6 participants. The findings indicate that boys with DMD can safely train their arms with dynamic arm support.

Physical Activity in Boys With Duchenne Muscular Dystrophy Is Lower and Less Demanding Compared to Healthy Boys

This study describes the amount of physical activity and perception of physical activity in boys with Duchenne muscular dystrophy (DMD) compared to healthy boys. A questionnaire described 6 domains of physical activity. Four Duchenne muscular dystrophy subgroups were made: early and late ambulatory, nonambulatory with relative good, or limited arm function. Eighty-four boys with Duchenne muscular dystrophy (15.0 ± 6.4 years) and 198 healthy boys (14.0 ± 4.3 years) participated. Daily activities were more passive for boys with Duchenne muscular dystrophy. Physical activity was less and low demanding compared to healthy boys. It decreased with disease severity (P < .05), whereas screen time increased (P < .05). Benefits of physical activity in boys with Duchenne muscular dystrophy were having fun and making friends. Barriers were lack of sport facilities and insufficient health. This study helps to quantify poor engagement in physical activity by boys with Duchenne muscular dystrophy, and demonstrates factors that contribute to it. Suggestions to stimulate physical activity are made.

Assisted 6-minute cycling test: An exploratory study in children

Introduction: The 6‐minute walk test (6MWT) is frequently used as an outcome measure for clinical trials in neuromuscular disease. Because this submaximal endurance test is not feasible for nonambulatory patients, the motor‐assisted 6‐minute cycling test (A6MCT) was developed. Methods: Nineteen children with neuromuscular disorders and children with OXPHOS‐dysfunction performed the a6MCT and the 6MWT to explore feasibility and construct validity. Test–retest reproducibility was evaluated within 3 weeks. Results: The assisted 6‐minute cycling test was feasible in 90% and 78% of the patients with a neuromuscular disorder and OXPHOS‐dysfunction, respectively. The A6MCT for legs correlated with the 6MWT in both patient groups. The assisted 6‐minute cycling showed good reproducibility for both legs and arms. Conclusions: This exploratory study indicates that the assisted 6‐minute cycling test is a promising outcome measure for patients with a neuromuscular disorder and patients with OXPHOS‐dysfunction. Muscle Nerve, 2015. Muscle Nerve 54: 232–238, 2016

What can we learn from assisted bicycle training in a girl with dystrophinopathy? A case study

In this case study, a 9-year-old ambulatory girl with dystrophinopathy due to a mosaic translocation mutation participated in dynamic training. Because the role of exercise is unclear in both boys and girls with dystrophinopathy, a recently developed assisted bicycle training regimen was evaluated for its feasibility and effectiveness in this girl. The girl trained at home, first 15 minutes with her legs and then 15 minutes with her arms, 5 times a week, for 24 weeks. This case study showed that the training was feasible and safe. In addition, we found that no physical deterioration occurred during the training period: the Motor Function Measure and the Assisted 6-Minute Cycling Test results remained stable. Slight improvements in quantitative muscle ultrasound intensity were found, indicating less fatty infiltration in the muscles. These results suggest that physical training could be beneficial in females with dystrophinopathy who express low levels of dystrophin.