Foot surgery for adults with Charcot-Marie-Tooth disease.

People with Charcot-Marie-Tooth (CMT) disease often undergo foot and ankle surgery, as foot deformities are common and cause a degree of functional limitations impairing quality of life. Surgical approaches are variable and there are no evidence-based guidelines. A multidisciplinary approach involving neurology, physical therapy and orthopaedic surgery is ideal to provide guidance on when to refer for surgical opinion and when to intervene. This review outlines the range of foot deformities associated with CMT, their clinical assessment, and their conservative and surgical and postoperative management.

A diagnostic framework to identify vestibular involvement in multi-sensory neurological disease.

BACKGROUND AND PURPOSE: Identifying vestibular causes of dizziness and unsteadiness in multi-sensory neurological disease can be challenging, with problems typically attributed to central or peripheral nerve involvement. Acknowledging vestibular dysfunction as part of the presentation provides an opportunity to access targeted vestibular rehabilitation, for which extensive evidence exists. A diagnostic framework was developed and validated to detect vestibular dysfunction, benign paroxysmal positional vertigo or vestibular migraine. The specificity and sensitivity of the diagnostic framework was tested in patients with primary mitochondrial disease. METHODS: Adults with a confirmed diagnosis of primary mitochondrial disease were consented, between September 2020 and February 2022. Participants with and without dizziness or unsteadiness underwent remote physiotherapy assessment and had in-person detailed neuro-otological assessment. The six framework question responses were compared against objective neuro-otological assessment or medical notes. The output was binary, with sensitivity and specificity calculated. RESULTS: Seventy-four adults completed the study: age range 20-81 years (mean 48 years, ±SD 15.05 years); ratio 2:1 female to male. The framework identified a vestibular diagnosis in 35 participants, with seven having two diagnoses. The framework was able to identify vestibular diagnoses in adults with primary mitochondrial disease, with a moderate (40-59) to very high (90-100) sensitivity and positive predictive value, and moderate to high (60-74) to very high (90-100) specificity and negative predictive value. CONCLUSIONS: Overall, the clinical framework identified common vestibular diagnoses with a moderate to very high specificity and sensitivity. This presents an opportunity for patients to access effective treatment in a timely manner, to reduce falls and improve quality of life.

Multicenter Validation of the Charcot-Marie-Tooth Functional Outcome Measure.

BACKGROUND AND OBJECTIVES: Charcot-Marie-Tooth disease type 1A (CMT1A), caused by a duplication of PMP22, is the most common hereditary peripheral neuropathy. For participants with CMT1A, few clinical trials have been performed; however, multiple therapies have reached an advanced stage of preclinical development. In preparation for imminent clinical trials in participants with CMT1A, we have produced a Clinical Outcome Assessment (COA), known as the CMT-Functional Outcome Measure (CMT-FOM), in accordance with the FDA Roadmap to Patient-Focused Outcome Measurement to capture the key clinical end point of function. METHODS: Participants were recruited through CMT clinics in the United States (n = 130), the United Kingdom (n = 52), and Italy (n = 32). To derive the most accurate signal with the fewest items to identify a therapeutic response, a series of validation studies were conducted including item and factor analysis, Rasch model analysis and testing of interrater reliability, discriminative ability, and convergent validity. RESULTS: A total of 214 participants aged 18-75 years with CMT1A (58% female) were included in this study. Item, factor, and Rasch analysis supported the viability of the 12-item CMT-FOM as a unidimensional interval scale of function in adults with CMT1A. The CMT-FOM covers strength, upper and lower limb function, balance, and mobility. The 0-100 point scoring system showed good overall model fit, no evidence of misfitting items, and no person misfit, and it was well targeted for adults with CMT1A exhibiting high inter-rater reliability across a range of clinical settings and evaluators. The CMT-FOM was significantly correlated with the CMT Examination Score (r = 0.643; p < 0.001) and the Overall Neuropathy Limitation Scale (r = 0.516; p < 0.001). Significantly higher CMT-FOM total scores were observed in participants self-reporting daily trips and falls, unsteady ankles, hand tremor, and hand weakness (p < 0.05). DISCUSSION: The CMT-FOM is a psychometrically robust multi-item, unidimensional, disease-specific COA covering strength, upper and lower limb function, balance, and mobility to capture how participants with CMT1A function to identify therapeutic efficacy.

Home-based multi-sensory and proximal strengthening program to improve balance in Charcot-Marie-Tooth disease Type 1A: A proof of concept study.

INTRODUCTION/AIMS: People with Charcot-Marie-Tooth Disease (CMT) frequently report problems with balance, which lead to an increased risk of falls. Evidence is emerging of training interventions to improve balance for people with CMT, but to date all have relied on clinic-based treatment and equipment. This proof-of-concept study explored whether a multi-modal program of proprioceptive rehabilitation and strength training can be delivered at home, to improve balance performance in people with CMT Type 1A. METHODS: Fourteen participants with CMT Type 1A were recruited into this randomized, two-arm study. Baseline assessments included measures of disease severity, posturography, physical function, and patient-reported outcome measurements. All participants received one falls education session. Participants were randomized to either 12 weeks of balance training or 12 weeks of usual activities. The intervention comprised a home-based, multi-sensory balance training and proximal strengthening program, supported by three home visits from a physiotherapist. RESULTS: Thirteen participants completed the study. The intervention was successfully implemented and well tolerated, with high participation levels. Functional measures of balance and walking showed strong effect sizes in favor of the training group. Posturography testing demonstrated moderate improvements in postural stability favoring the intervention group. Inconsistent changes were seen in lower limb strength measures. DISCUSSION: The intervention was feasible to implement and safe, with some evidence of improvement in balance performance. This supports future studies to expand this intervention to larger trials of pragmatic, home-delivered programs through current community rehabilitation services and supported self-management pathways.

Protocol for a hybrid II study exploring the feasibility of delivering, evaluating, and implementing a self-management programme for people with neuromuscular diseases at a specialist neuromuscular centre.

BACKGROUND: Self-management support (SMS) forms a central pillar in the management of long-term conditions. It is firmly aligned with UK health policy but there is a paucity of evidence exploring how it is enacted in the context of neuromuscular diseases (NMDs). Bridges is a SMS programme originally developed in stroke. A new version of the programme (Neuromuscular Bridges) has recently been co-designed with people with lived experience of NMD and requires evaluation. The implementation of SMS is inherently complex with potential barriers at the level of the patient, provider, and wider organisation. The success of implementing programmes can be highly dependent on context, indicating a rationale for considering implementation determinants at an early stage. This study aims to explore the feasibility of (1) delivering, (2) evaluating, and (3) implementing Neuromuscular Bridges at a specialist neuromuscular centre. METHODS: This study employs a hybrid II design underpinned by Normalisation Process Theory (NPT), which has been used prospectively to inform the implementation plan and will also inform the analysis. The feasibility of delivering, evaluating, and implementing Neuromuscular Bridges will be assessed using a single-arm pre-post design. In terms of delivery and evaluation, we will explore acceptability, demand within the service, performance of outcome measures, recruitment, and retention. Implementation strategies have been selected from a refined taxonomy of strategies, mapped to NPT, and targeted at known barriers and facilitators at the specialist centre that were identified from preliminary stakeholder engagement activities. The impact of the strategy bundle on fidelity, acceptability, appropriateness, and adoption will be evaluated using qualitative interviews, administrative data, surveys, and a notes audit. CONCLUSIONS: This this study will provide valuable feasibility data on a co-designed SMS programme for people with NMDs that will be used to inform a larger implementation study, requirements for embedding it in a specialist centre, and rollout to other specialist centres. Using hybrid methodology at the feasibility stage is unusual and this study will provide important insights into the usefulness of taking this approach at this point in the research pipeline. TRIAL REGISTRATION: ISRCTN Trial ID: ISRCTN14208138 . Date registered: 18/08/2021.

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.

Cardiopulmonary exercise performance and factors associated with aerobic capacity in neuromuscular diseases.

INTRODUCTION/AIMS: Aerobic deconditioning, due to lower levels of physical activity, could impact independence for people with neuromuscular conditions. We report the maximal cardiopulmonary response in a cohort of people with Charcot Marie Tooth disease type 1A (CMT 1A) and inclusion body myositis (IBM). We also explored potential predictors of aerobic capacity with measures of physical impairment and functional performance. METHODS: Participants underwent maximal cardiopulmonary exercise testing (CPET) using a semi-recumbent cycle ergometer. Data were analyzed to determine the peak O2 consumption (VO2 peak), anaerobic threshold (AT), maximum heart rate (MHR), ventilatory equivalent for CO2 slope (VE /VCO2 ), and respiratory exchange ratio (RER). Impairment, functional and patient reported measures were also recorded. Predicted CPET variables were calculated based on published normative data for age, gender, and weight. RESULTS: Twenty-two people with CMT and 17 people with IBM were recruited. Both groups showed significantly lower VO2 peak, MHR, AT, and VE /VCO2 . The CMT group overall performed better than the IBM group, with significantly higher VO2 peak, MHR, and AT, but lower VE /VCO2. Linear regression analysis demonstrated that VO2 peak was related to body fat percentage and 6-min walk distance for both groups, and steps per day for the IBM group. DISCUSSION: Lower than predicted CPET variables were observed that were not explained by cardiopulmonary limitations or reduced effort, implicating peripheral factors in limiting the cycling task. Regression analysis implied prediction of VO2 peak by body fat percentage and 6-min walk distance. Six-minute walk distance could be a potential proxy measure of cardiopulmonary fitness.

Community exercise is feasible for neuromuscular diseases and can improve aerobic capacity.

OBJECTIVE: The aim of this phase 2 trial was to ascertain the feasibility and effect of community-based aerobic exercise training for people with 2 of the more common neuromuscular diseases: Charcot-Marie-Tooth disease type 1A (CMT) and inclusion body myositis (IBM). METHODS: A randomized single-blinded crossover trial design was used to compare a 12-week aerobic training program using recombinant exercise bicycles compared to a control period. The training occurred 3 times per week in community gyms local to the participants. Support was available from trained gym staff and a research physiotherapist. The 2 disease groups were analyzed separately. The primary outcome measure was peak oxygen uptake (VO2 peak) during a maximal exercise test, with secondary measures of muscle strength, function, and patient-reported measures. RESULTS: Data from 23 people with CMT and 17 people with IBM were included in the analysis. Both disease groups had high levels of participation and demonstrated improvements in VO2 peak, with a moderate effect size in the CMT participants (Cohen d = 0.53) and a strong effect size in the IBM group (Cohen d = 1.72). No major changes were observed in the secondary outcome measures. Qualitative interviews revealed that participants valued the support of gym instructors and the research physiotherapists in overcoming challenges to participation. CONCLUSION: Twelve weeks of aerobic training in community gyms was feasible, safe, and improved aerobic capacity in people with CMT and IBM. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with CMT type 1A and IBM, an aerobic training program increases aerobic capacity.

Frequency and circumstances of falls for people with Charcot-Marie-Tooth disease: A cross sectional survey.

OBJECTIVE: People with Charcot-Marie-Tooth (CMT) disease may be at risk of falls due to distal muscle weakness and sensory impairment. We aimed to understand the frequency of falls in a cohort, where they occurred, injury and to what people attributed the possible cause. DESIGN: A cross-sectional survey design was used. It was sent by post to ascertain the frequency of falls and near falls, plus the circumstances of the last three falls events they could recall. SETTING: The survey was administered to 252 people with CMT who were patients at a specialist neuromuscular centre. PARTICIPANTS: People were approached who had a clinical diagnosis by a neuromuscular specialist neurologist. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The Falls Event Questionnaire. RESULTS: Responses were received from 107 people with CMT. Falls and near falls were reported by 86% of survey respondents. The majority of falls occurred at home, and muscular weakness appeared to be blamed the most, with participants describing tripping due to foot drop or joints giving way. A similar pattern was observed for near falls, but they tended to be more frequent. Moderate and major injuries were relatively rare, with the majority of falls resulting in scrapes and bruises or the faller feeling shaken by the experience. DISCUSSION: The impact of falls is far reaching, in terms of injury risk and the consequences of the fear of falling. Interventions to improve balance and reduce falls are an important rehabilitation focus for people with CMT.

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.

A pilot study of proximal strength training in Charcot-Marie-Tooth disease.

Gait analysis of people with Charcot-Marie-Tooth (CMT) disease revealed proximal adaptive gait strategies to compensate for foot drop. We previously demonstrated that hip flexor muscle fatigue can limit walking endurance. This pilot study used a single-blinded cross over design to investigate the effect of a 16-week home-based programme of resistance training on hip flexor muscle strength. Measures of walking endurance, gait speed, exertion, fatigue, and general activity were also recorded. The exercise protocol was based on American College of Sports Medicine recommendations. A mixed effects model was used for analysis. Twenty-six people finished the study, with average reported exercise participation of 93%. No negative effects of exercise were observed. Significant increase in hip flexor muscle strength was observed on the left, but not the right. No changes were observed in walking speed and endurance measures. This pilot study of home-based resistance training showed a modest improvement in hip strength but only on one side. The lack of a more significant improvement and no improvement in walking measures suggests that this training protocol may not be optimal for people with CMT and that patients may need to stratified differently for training studies in CMT.

Exploring the experience of fatigue in people with Charcot-Marie-Tooth disease.

This qualitative study explored the phenomenon of fatigue for people with Charcot-Marie-Tooth disease, while acknowledging the triggers, impact and strategies people have developed to manage this symptom in daily life. A phenomenological approach was used to explore the experience of fatigue. Participants were recruited from a support group. Twenty-five people participated in three focus groups. Group interviews were tape recorded and independently transcribed. Transcripts were coded and emerging themes were highlighted. Four areas were explored and themes identified within them. Fatigue descriptions: energy depletion, overwhelming nature, variations in fatigue and fatigue as an abnormal experience; triggers of fatigue: activity, stress and mental concentration; impact of fatigue on: physical abilities, mood, guilt and frustration, isolation and concerns about how they were perceived by others; strategies to manage fatigue: coping with symptoms; planning ahead; deception; and reducing symptoms. This study revealed that fatigue is an overwhelming experience for people with Charcot-Marie-Tooth disease that impacts on many areas of their lives. People may require significant adjustment that could be facilitated by fatigue management approaches. In addition, exercise may have potential to reduce the symptoms of fatigue in some people.

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.

Comparing gait performance of people with Charcot-Marie-Tooth disease who do and do not wear ankle foot orthoses.

BACKGROUND AND PURPOSE: Ankle foot orthoses (AFOs) are commonly prescribed for people with Charcot-Marie-Tooth (CMT) disease. Scant evidence exists to guide the type and timing of orthotic prescription. This study explores the latter issue by investigating the differences in presentation and gait function of people with CMT disease who wore AFOs for daily mobility (n = 11) and a group who did not (n = 21). The aim was to see if there was a difference in the characteristics in people who regularly wear AFOs. METHODS: Primary measures of gait function were a 10-m timed walk (comfortable and maximum speed) and a 6-minute walk test. Means of the variables were compared using independent t-tests. Secondary measures included disease severity, lower limb muscle strength, sensory impairment, walking effort, fatigue severity and perceived walking ability. RESULTS: AFO wearers walked slower with higher effort. They also had greater disease severity, weaker leg muscles and perceived greater walking difficulty. Subjects not wearing AFOs showed significant relationships between gait variables and muscle strength, whereas AFO wearers showed significant relationships between gait variables and perceived walking ability, fatigue severity and effort. CONCLUSIONS: People who regularly wore AFOs were more severely affected, had a slower maximum walking speed, higher energy cost of walking and worse perceived walking ability. Walking ability in this group was related to fatigue, perceived exertion during walking and perceived walking ability. Gait function of people not using AFOs was determined by lower limb muscle function. People prescribed AFOs, those who do not wear them and those not prescribed AFOs were similar in presentation, suggesting that people choose to wear orthoses when their condition becomes sufficiently severe.

Rehabilitation in practice: management of lower motor neuron weakness.

This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is 'The trainee consistently demonstrates a knowledge of the pathophysiology of various specific impairments including lower motor neuron weakness' and 'management approaches for specific impairments including lower motor neuron weakness'.This article explores weakness as a lower motor symptom. Weakness as a primary impairment of neuromuscular diseases is addressed, with recognition of the phenomenon of disuse atrophy, and how weakness impacts on the functional abilities of people with myopathy and neuropathy. Interventions to reduce weakness or address the functional consequences of weakness are evaluated with consideration of safety and clinical application. LEARNING OUTCOMES: This paper will allow readers to: (1) appraise the contribution of research in rehabilitation of lower motor neuron weakness to clinical decision making and (2) engage with the issues that arise when researching rehabilitation interventions for lower motor neuron weakness. AIM OF ARTICLE: Impairments associated with neuromuscular conditions can lead to significant functional difficulties that can impact on a person's daily participation. This article focuses on the primary impairment of weakness and explores the research evidence for rehabilitation interventions that directly influence weakness or address the impact of weakness on function.

Hip flexor fatigue limits walking in Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (CMT) disease results in distal lower limb weakness that affects walking. In this study we assess the role of the hip flexors in compensating for distal weakness while walking and the effects of prolonged walking on these putative compensatory strategies. Eighteen subjects with CMT disease were compared with 14 matched controls while they walked on a treadmill to a predetermined point of perceived effort. A significant reduction was observed in peak hip flexor velocity during walking and hip flexor maximal voluntary contraction. In a second session following selective fatigue of the hip flexors, hip flexor velocity decreased immediately on walking, and walking duration was greatly reduced. This study suggests that hip flexors compensate for distal weakness and that fatigue in the hip flexors can limit walking duration. Treatments directed toward improving proximal muscle strength may therefore help to delay onset of hip flexor fatigue and thus prolong walking duration.