The experience of falls and balance impairment for people with Charcot-Marie-Tooth disease

People with Charcot Marie Tooth disease (CMT) have impairments of balance and may fall more frequently than those without the condition. This qualitative study aimed to explore the experiences of falling and poor balance through focus group interviews. Participants were recruited through local and national meetings of the CMT United Kingdom support group. Three focus groups took place, including 25 adults with CMT in total. Thematic analysis revealed five main themes: frequent falling; cognitive burden of walking; environmental issues; external support; getting off the floor; perception of others. Participants described the physical issues of poor balance and falling, such as frequency, challenging physical environments and difficulty getting up after a fall. In addition, fear and embarrassment were discussed along with the impact on daily activities and participation. Physical and psychological factors need to be considered when designing falls management interventions for this group

A study of physical activity comparing people with Charcot Marie Tooth disease to normal control subjects

PURPOSE: Charcot Marie Tooth disease (CMT) describes a group of hereditary neuropathies that present with distal weakness, wasting and sensory loss. Small studies indicate that people with CMT have reduced daily activity levels. This raises concerns as physical inactivity increases the risk of a range of co- morbidities, an important consideration in the long-term management of this disease. This study aimed to compare physical activity, patterns of sedentary behavior and overall energy expenditure of people with CMT and healthy matched controls. METHODS: We compared 20 people with CMT and 20 matched controls in a comparison of physical activity measurement over seven days, using an activity monitor. Patterns of sedentary behavior were explored through a power law analysis. RESULTS: Results showed a decrease in daily steps taken in the CMT group, but somewhat paradoxically, they demonstrate shorter bouts of sedentary activity and more frequent transitions from sedentary to active behaviors. No differences were seen in energy expenditure or time spent in sedentary, moderate or vigorous activity. CONCLUSION: The discrepancy between energy expenditure and number of steps could be due to higher energy requirements for walking, but also may be due to an over-estimation of energy expenditure by the activity monitor in the presence of muscle wasting. Alternatively, this finding may indicate that people with CMT engage more in activities or movement not related to walking. Implications for Rehabilitation Charcot-Marie-Tooth disease: • People with Charcot-Marie-Tooth disease did not show a difference in energy expenditure over seven days compared to healthy controls, but this may be due to higher energy costs of walking, and/or an over estimation of energy expenditure by the activity monitor in a population where there is muscle wasting. This needs to be considered when interpreting activity monitor data in people with neuromuscular diseases. • Compared to healthy controls, people with Charcot-Marie-Tooth disease had a lower step count over seven days, but exhibited more frequent transitions from sedentary to active behaviors • High Body Mass Index and increased time spent sedentary were related factors that have implications for general health status. • Understanding the profile of physical activity and behavior can allow targeting of rehabilitation interventions to address mobility and fitness

Ongoing developments in sporadic inclusion body myositis

Sporadic inclusion body myositis (IBM) is an acquired muscle disorder associated with ageing, for which there is no effective treatment. Ongoing developments include: genetic studies that may provide insights regarding the pathogenesis of IBM, improved histopathological markers, the description of a new IBM autoantibody, scrutiny of the diagnostic utility of clinical features and biomarkers, the refinement of diagnostic criteria, the emerging use of MRI as a diagnostic and monitoring tool, and new pathogenic insights that have led to novel therapeutic approaches being trialled for IBM, including treatments with the objective of restoring protein homeostasis and myostatin blockers. The effect of exercise in IBM continues to be investigated. However, despite these ongoing developments, the aetiopathogenesis of IBM remains uncertain. A translational and multidisciplinary collaborative approach is critical to improve the diagnosis, treatment, and care of patients with IBM

221st ENMC International Workshop : Foot Surgery in Charcot-Marie-Tooth disease June 10th-12th, 2016 Naarden, The Netherlands

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Neuromuscular disease genetics in under-represented populations: increasing data diversity

Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses ‘solved’ or ‘possibly solved’ ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% ‘solved’ and ∼13% ‘possibly solved’ outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally

Neuromuscular disease genetics in underrepresented populations : increasing data diversity

DATA AVAILABILITY : At the end of the study, participants de-identified exome and genome data will be archived in the European Molecular Biology Laboratory European Bioinformatics Institute’s European Genome-Phenome Archive (EMBL EBI EGA), with community access to this and selected de-identified REDCap data managed via an ICGNMD Data Access Committee.Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses 'solved' or 'possibly solved' ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% 'solved' and ∼13% 'possibly solved' outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally.This work was supported by a Medical Research Council strategic award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) MR/S005021/1. Additional ICGNMD support including travel and subsistence costs was received from the National Brain Appeal (UK Charity 290173) and University College London Global Engagement Funds. Fellowships for R.S.S.F. and K.N. were funded by the Guarantors of Brain (UK Charity 1197319). The authors acknowledge and are grateful for: conference bursaries from the World Muscle Society to R.S.S.F. S.R., K.N., O.Y.K., P.J.T., V.V.Y. S.V.D.M. and R.L. are members of the European Reference Network for Rare Neuromuscular Diseases (ERN EURO-MND). M.P.K.: National Institute of Neurological Disorders and Stroke (1K23NS112463), American Association of Neuromuscular & Electrodiagnostic Medicine Development Award and Allen Foundation. D.B.: National Institute of Neurological Disorders and Stroke (K23NS117310) and support from Biogen for the KCTN1 Natural History Study. G.M.R.: University College London and UCLH Biomedical Research Centre funding, Health Education England and University College London Hospitals NHS Foundation Trust Innovation Fund. R.M.F., R.W.T. and K.P.: Wellcome core support (203105/Z/16/Z). R.M.F. received additional support from the Lily Foundation and the Leigh Syndrome International Consortium. A.T.: EU Horizon 2020 research and innovation Solve-RD project, No. 779257. F.H.W., M.S., M.B. and A.V.: South African Medical Research Council award ‘The genetics of Neuromuscular Diseases in South African patient populations: the ICGNMD study’. K.T. is funded by a J. C. Bose Fellowship, Science and Engineering Research Board (SERB) Department of Science and Technology, India. P.G. is supported by the Centre for DNA Fingerprinting and Diagnostics (CDFD) Core Research Grant, Department of Biotechnology, Government of India. R.H.: Wellcome award 109915/Z/15/Z, UK Medical Research Council award MR/N025431/1, the Lily Foundation, Evelyn Trust Research Grant (Ref 19/14), Action for A-T and UK Research and Innovation Newton Fund (MR/NO27302/1). P.F.C.: Wellcome awards 212219/Z/18/Z and 224486/Z/21/Z, UK Medical Research Council awards MC_PC_21046, MR/S035699/1 and MR/ S01165X/1, LifeArc Philanthropic Fund, NIHR BioResource for Translational Research in Common and Rare Diseases, Alzheimer’s Society, NIHR BioResource for Genes and Cognition and Leverhulme Trust. R.D.S.P.: UK Medical Research Council MR/ S002065/1 and MC_PC_21046, and the Lily Foundation. H.H.: UK Medical Research Council, Wellcome, UCLH Biomedical Research Centre (NIHR-BRC), Rosetrees Trust, and SOLVE-RD. M.M.R.: Wellcome grant G104817, National Institute of Neurological Disorders and Stroke and Office of Rare Diseases grants U54NS065712 and 1UOINS109403-01 and Muscular Dystrophy Association grant.https://www.edusoft.ro/brain/index.php/brainam2024Paediatrics and Child HealthSDG-03:Good heatlh and well-bein

Exercise in myositis: What is important, the prescription or the person?

Our aim for this narrative review was to undertake a search of studies into exercise for people living with Idiopathic Inflammatory myopathies (IIM). We explored the strength of existing evidence with a particular consideration for the implications for people living with IIM and what is important to them. The search strategy from the 2021 Cochrane Physical Activity review in neuromuscular disease was used, and we selected articles that included people with IIM, including Dermatomyositis (DM), Inclusion Body Myositis (IBM), Immune Mediated Necrotising Myopathy (IMNM) [also known as necrotizing autoimmune myopathy (NAM)], and Polymyositis (PM). 2967 records were screened and 16 were included in this review. Safety of exercise was demonstrated in nine articles, using a range of measures of disease activity, serum creatine kinase, indicators of inflammation, pain, or fatigue. Two studies that took muscle biopsies showed no evidence of increased inflammation. Aerobic exercise protocols were used in 8 studies across conditions and demonstrated improvements in cardiorespiratory fitness or exercise capacity. Six studies of strength training observed improvements in muscle function, with two studies reporting muscle biopsy results of amplified immune response and up regulation of genes related to recycling of damaged proteins. Nine of 13 studies that measures functional outcomes showed significant improvements, and evidence for behaviour change was observed in a study of a self-management intervention. The evidence of safety and effect of training is reassuring and welcome, and we now need to explore how we support people to incorporate exercise and physical activity longer term into active lifestyles

A randomised controlled feasibility trial of the Graded Repetitive Arm Strengthening Programme delivered to survivors of stroke at home

Background/aims This randomised controlled feasibility trial evaluated the recruitment, engagement and effect of the Graded Repetitive Arm Strengthening Programme in a community rehabilitation setting in London, UK. Methods A parallel design was used to ascertain the effect of the Graded Repetitive Arm Strengthening Programme plus standard care compared to standard care only over four weeks. Eleven participants were randomised using permuted blocks randomisation following discharge, with six participants allocated to the Graded Repetitive Arm Strengthening Programme (study) group and five to the standard care (control) group. The primary outcome was the Wolf Motor Function Test. Secondary outcomes were the Motor Activity Log and grip strength. Results A total of five participants in each group were analysed as one person withdrew from the study group. Participants in the study group gave more time to supplementing their exercise time independently (160% more vs 42% more). Most Wolf Motor Function Test tasks' time and function data showed a small difference in favour of the Graded Repetitive Arm Strengthening Programme. Results were re-examined using a Bayesian structural equation model to quantify changes in the underlying impairment. This showed significant differences: 40% faster task completion (P<0.001, 95% confidence level [CI] 30–49%), mean improvement of 0.54 on the five-point functional ability score (P<0.001, 95% CI 0.39–0.68), odds ratio of 0.05 for non-completion of task (P<0.001, 95% CI 0.02–0.14). Conclusions This study has shown that implementing the Graded Repetitive Arm Strengthening Programme is feasible and may have a greater effect on outcomes when delivered as part of care in a community rehabilitation setting. The analysis of the Wolf Motor Function Test was also critiqued

Foot drop splints improve proximal as well as distal leg control during gait in Charcot-Marie-Tooth disease

Introduction: During walking, people with Charcot-Marie-Tooth (CMT) disease may compensate for distal weakness by using proximal muscles. We investigated the effect of different AFOs on distal leg control and proximal compensatory actions. Methods: Fourteen people with CMT were tested while wearing 3 types of ankle-foot orthosis (AFO) bilaterally compared with shoes alone. Walking was assessed using three-dimensional gait analysis. Stiffness of the splints was measured by applying controlled 5-degree ankle stretches using a motor. Results: The results showed that each AFO significantly stiffened the ankle and increased ankle dorsiflexion at foot clearance compared with shoes alone. At push off, peak ankle power generation was reduced, but only with 1 type of AFO. A significant decrease in hip flexion amplitude during the swing phase was observed with all 3 AFOs. Conclusions: These results indicate that AFOs reduce foot drop and remove the need for some proximal compensatory action