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.

Physical activity of children with a mitochondrial disease compared to children who are healthy.

PURPOSE: To compare the physical activity of a group of children with mitochondrial myopathy (MM) with children who are healthy and to evaluate the suitability of different measurement tools. METHODS: The physical activity of 6 children with MM and 10 children who are healthy was measured using accelerometry, heart rate monitoring, video observation, rating of their fatigue, and 2 questionnaires about their physical activity and quality of life. RESULTS: The children with MM spent less time in moderate to vigorous activity, and their activity level measured with the accelerometer was lower than the children who are healthy. Also, the children with MM indicated a higher level of fatigue and a lower quality of life. CONCLUSIONS: Children with MM are on average less physically active, report a higher level of fatigue, and a lower quality of life than children who are healthy.

Peripheral neuropathy associated with mitochondrial disease in children.

Mitochondrial diseases in children are often associated with a peripheral neuropathy but the presence of the neuropathy is under-recognized because of the overwhelming involvement of the central nervous system (CNS). These mitochondrial neuropathies are heterogeneous in their clinical, neurophysiological, and histopathological characteristics. In this article, we provide a comprehensive review of childhood mitochondrial neuropathy. Early recognition of neuropathy may help with the identification of the mitochondrial syndrome. While it is not definite that the characteristics of the neuropathy would help in directing genetic testing without the requirement for invasive skin, muscle or liver biopsies, there appears to be some evidence for this hypothesis in Leigh syndrome, in which nuclear SURF1 mutations cause a demyelinating neuropathy and mitochondrial DNA MTATP6 mutations cause an axonal neuropathy. POLG1 mutations, especially when associated with late-onset phenotypes, appear to cause a predominantly sensory neuropathy with prominent ataxia. The identification of the peripheral neuropathy also helps to target genetic testing in the mitochondrial optic neuropathies. Although often subclinical, the peripheral neuropathy may occasionally be symptomatic and cause significant disability. Where it is symptomatic, recognition of the neuropathy will help the early institution of rehabilitative therapy. We therefore suggest that nerve conduction studies should be a part of the early evaluation of children with suspected mitochondrial disease.

Physiological demands of therapeutic horseback riding in children with moderate to severe motor impairments: an exploratory study.

PURPOSE: To examine energy expenditure at rest and during a single therapeutic horseback riding (THR) session in children with moderate to severe motor impairments. METHODS: Heart rate (HR), oxygen uptake (.VO2), and minute ventilation (.VE) were measured continuously during a 10-minute rest period and during a typical THR session. RESULTS: Seven children (4 males, mean age 12.3 ± 3.5 years) completed the protocol. Significant increases from rest were seen for mean HR, .VO2, .VE, and energy expenditure. Based on .VO2, 43.3 ± 24.3% of the THR session consisted of sedentary, 44.4 ± 13.4% of light, and 12.3 ± 21.8% of moderate to vigorous activity intensity, with large interindividual differences. CONCLUSIONS: The physiological demands of THR in children with moderate to severe motor impairments are moderate. However, considering the short duration of maintaining moderate to vigorous exercise activity during THR in combination with the low training frequency, group data indicate that it is unlikely that THR will improve cardiopulmonary fitness in these children.

Everyday Activities for Children with Mitochondrial Disorder: A Retrospective Chart Review.

BACKGROUND: Engagement in everyday activities is important for the health and wellbeing of children. Children with mitochondrial disorders have impaired energy production leading to limitations in activity. It is unknown which activities these children perform and if the nature of activities of low-functioning children differs from average-functioning children. Therefore, this pilot study explored the activities reported in patient records of a heterogeneous group of children with genetically confirmed mitochondrial disorders. METHODS: A retrospective qualitative directed content analysis by health care professionals reported activities (as part of their professional reasoning obligations) in hospital patient records of children with mitochondrial disorder. RESULTS: Seventeen patient records, presenting notes on capacities and performed activities, showed an overview of everyday activities that covered the categories: self-care, house chores, therapy, school, computing, hobby, play, sports, and mobility/transport. The activity categories of low-functioning children did not differ from average-functioning children, although descriptions of specific activities differed between groups. CONCLUSION: This pilot exploration indicates that the types of activities that children with mitochondrial disorders perform are not necessarily linked to the child's impairments. However, differences in levels of independence, assistive device usage, and energy costs seem to exist. Future research should address the child's perspective on, and meaning of, activity performances.

Lactate production upon short-term non-ischemic forearm exercise in mitochondrial disorders and other myopathies.

BACKGROUND: The nonischemic forearm exercise test (NIFET) has been shown to be as effective as the classic ischemic forearm exercise test (IFET) in the diagnosis of patients with McArdle disease. Recently, the lactate increase normalized to the mechanical energy production in NIFET was suggested to have a intermediate sensitivity and satisfactory specifity for the screening of mitochondrial disorders. METHODS: NIFET at 80% maximal contraction force (MCF) was performed in normal controls (n = 41), patients with mitochondrial disorders (n = 15) and other myopathies (diseased controls, n = 20). 26 healthy volunteers also underwent IFET at 80% MCF. The ratio of lactate increase and workload was defined as specific lactate production (mmol x s/N x l). RESULTS: In normal controls there was no significant different lactate increase during NIFET and IFET. The workload performed showed only a weak significant positive correlation with the lactate increase in the NIFET in normal controls (r(2) = 0.20) but not in IFET and NIFET with patients. A moderate negative correlation of specific lactate production and the absolute workload was found in all groups and in both protocols (r(2) = 0.22-0.34). The specific lactate production was highest in patients with other myopathies, intermediate in patients with mitochondrial disorders and lowest in normal controls. NIFET showed a sensitivity of only 20 % and a specifity of 95% for normal controls, but only 75 % for diseased controls. CONCLUSION: The specific lactate production during NIFET is neither sufficiently specific nor sensitive for the diagnosis of mitochondrial disorders. Increased specific lactate production during rest-to-work transition period might be caused by increased acetyl group deficits.

Physical Exercise and Brain Mitochondrial Fitness: The Possible Role Against Alzheimer's Disease.

Exercise is one of the most effective strategies to maintain a healthy body and mind, with particular beneficial effects of exercise on promoting brain plasticity, increasing cognition and reducing the risk of cognitive decline and dementia in later life. Moreover, the beneficial effects resulting from increased physical activity occur at different levels of cellular organization, mitochondria being preferential target organelles. The relevance of this review article relies on the need to integrate the current knowledge of proposed mechanisms, focus mitochondria, to explain the protective effects of exercise that might underlie neuroplasticity and seeks to synthesize these data in the context of exploring exercise as a feasible intervention to delay cognitive impairment associated with neurodegenerative conditions, particularly Alzheimer disease.

Computer control using human intracortical local field potentials.

We describe the use of human cortical control signals to operate two assistive technology tools--a virtual keyboard speller and a computer-simulated digit. The cortical signals used for control are local field potentials recorded through an implanted neurotrophic electrode. In this system, the patients' cortical signals are transmitted wirelessly to a receiver and translated by computer software into either a computer cursor movement (for the virtual keyboard) or flexion of a cyber digit on a virtual hand. This report focuses on the progress of two subjects toward effective use of their "virtual" neuro-prosthetic devices to meet their assistive technology needs.

Cochlear implantation in mitochondrial deafness due to A7445G mutation.

OBJECTIVE: This study aimed to determine if cochlear implantation (CI) improved speech discrimination in the New Zealand pedigree with the A7445G mitochondrial DNA (mtDNA) mutation and sensorineural hearing loss (SNHL). METHODS: Nine patients had their speech discrimination and pure tone audiograms evaluated. Pre- and post-implant results were compared. Type of CI and patient age at implantation was recorded. RESULTS: Speech discrimination testing shows greatly improved functional hearing after CI in this group of patients. DISCUSSION: Individuals with mtDNA-related SNHL should be identified by screening and offered assessment for CI suitability because functional hearing improves after CI.

Fat metabolism during exercise in patients with mitochondrial disease.

OBJECTIVE: To determine whether patients with defects of the respiratory chain have metabolic adaptations that promote a preferential use of fats or carbohydrates, similar to what is observed in metabolic myopathies affecting glycolysis or fat oxidation. DESIGN: Causation and case-control study. Fat metabolism was determined by means of indirect calorimetry and stable isotope technique in patients and healthy subjects. Patients carried various types and loads (mean [SE], 72% [5%]) of mitochondrial DNA (mtDNA) mutations in skeletal muscle. All subjects exercised at the same absolute workload (mean [SE], 65 [10] W), corresponding to 72% (in patients) and 30% (in healthy subjects) of maximum oxygen consumption. SETTING: Neuromuscular research unit. PARTICIPANTS: Ten patients with mtDNA mutations and 10 sex-matched healthy subjects. MAIN OUTCOME MEASURES: Fat turnover, plasma concentrations of palmitate and total free fatty acids, glucose mobilization, and total carbohydrate oxidation. RESULTS: Fat turnover and plasma concentrations of palmitate and total free fatty acids were similar in patients and healthy subjects at rest and during exercise. In line with the higher relative workload of the patients, glucose mobilization and total carbohydrate oxidation were higher in the patients compared with the healthy subjects. CONCLUSION: During moderate-intensity exercise, the balance between fat and carbohydrate use in patients with mtDNA mutations matches that seen in healthy subjects, indicating that manipulating dietary fat and carbohydrate content is not a feasible therapeutic option to improve exercise intolerance in these disorders.