Exercise Physiology and Ergometric Interventions and Guidelines In Neurologic Disorders

Normal exercise physiology and bioenergetic metabolism: Exercise guidelines in children with fatty acid oxidation (FAO) and glycolytic/glycogenolytic disorders
Ingrid Tein
Resting muscle derives its primary energy source from FAO. At rest, glucose utilization accounts for 10% to 15% of total O2 consumption. Type I, 2A and 2B muscle fibres have unique metabolic characteristics and functional roles. Choice of bioenergetic pathway in working muscle depends on type, intensity, and duration of exercise, but also on diet & physical conditioning. In the first 20 sec of short burst mod->high exercise, high-energy phosphates are used to regenerate ATP. This is followed by muscle glycogen breakdown, indicated by a sharp rise in lactate in the first 10 min. Blood lactate levels then drop as muscle triglycerides and blood-borne fuels are used. After 90 min, the major fuels are glucose and free fatty acids (FFAs). During 1 to 4 hrs of mild to moderate prolonged aerobic exercise, muscle uptake of FFAs increases ~70%, and after 4 hrs, FFAs are used twice as much as carbohydrates (CHO). In glycolytic/glycogenolytic disorders, we advise individuals to exercise at low intensity and to go slow for 10-12 min until they reach their ‘second wind’ from hepatic glycogenolysis in myophosphorylase deficiency and from serum FFAs for ATP generation from FAO. In FAO disorders we recommend a high CHO drink/snack prior to exercise followed by 15 min of high intensity exercise utilizing anaerobic glycolysis and then a rest for a few min with another high CHO drink/snack, followed by a second 15 min period of high intensity exercise, not exceeding 30 min in total at one time.

Exercise interventions in children with neuromuscular disorders
Haluk Topaloglu
Maintaining  activity in this group of disorders is considered essential for quality of life. This has been scientifically verified. I will give three examples. In Duchenne muscular dystrophy exercise leads to release of peroxisome proliferator-activated receptor (PPAR) γ coactivator-1α 164  (PGC-1α) in the serum. This molecule is known to balance negative oxidative stress and inflammatory signals. Increased expression of modifiers such as ostepontin, alpha-actinin 3 and others lead to autophagy regulation and elevated mitochondrial biogenesis. Spinal muscular atrophy is a multisystemic splicesome disorder. Treatments should aim towards muscle and alpha motor neurons. Endurance and resistance training lead to increased mitochondrial synthesis. In mouse models with exercise, there is an extended life span up to 60% following  elevated SMN protein levels in the spinal cord, decreased loss of alpha motor neurons, preserved muscle bulk and healthy neuromuscular junctions. IGF may have an additional role. In myotonic dystophy, AMPK, a cellular energy regulator is the mainstay. PGC-1 alpha is also cardinal along with mitochondrial dynamics. For congenital myopathies and hereditary neuropathies, similar principles apply. In this group of disorders, activity should be tailored to the individual child, eg 30 min a  day is adequate. Maintenance of physical activity in a child with a chronic neuromuscular disorder is also key for preservation of mental health & sense of accomplishment.

Exercise interventions in children with cerebral palsy (CP)
Bernard Dan
The WHO recommends strongly that children and adolescents with disabilities engage daily into vigorous, mostly aerobic physical activity, or at least 3 days a week. Yet voluntary exercise has been sparsely and variably implemented in intervention programmes for children and adolescents with cerebral palsy (CP). The significant effect of aerobic exercise, e.g. walking, running, treadmill training, sports and aquatic exercises, has been demonstrated on aerobic capacity, balance, gross motor function, mobility, and participation (no effect demonstrated to date on muscle strength, spasticity, gait parameters or quality of life compared to ‘usual care’ or other interventions). The optimal dose is currently unknown. There is mounting evidence that adequately dosed resistance training can alter muscle architecture as well as increase muscle force and power in this population, though the mechanisms underlying specific changes (e.g. in muscle size or fascicle length) remain to be clearly understood. Studies of skeletal muscle mitochondrial energy metabolism have started to provide clues that might help design better intervention  strategies. Such research has involved relatively small samples to date, but they provide indications of mitochondrial dysfunction and of an ageing pattern of gene expression in skeletal muscle from patients with CP. This provides further rationale for encouraging exercise, and possible enhancement of the effect with targeted pharmacological agents.