Biomechanics

Biomechanics is a vast discipline within the field of Biomedical Engineering. It explores the underlying mechanics of how biological and physiological systems move. It encompasses important clinical applications to address questions related to medicine using engineering mechanics principles. Biomechanics includes interdisciplinary concepts from engineers, physicians, therapists, biologists, physicists, and mathematicians. Through their collaborative efforts, biomechanics research is ever changing and expanding, explaining new mechanisms and principles for dynamic human systems. Biomechanics is used to describe how the human body moves, walks, and breathes, in addition to how it responds to injury and rehabilitation. Advanced biomechanical modeling methods, such as inverse dynamics, finite element analysis, and musculoskeletal modeling are used to simulate and investigate human situations in regard to movement and injury. Biomechanical technologies are progressing to answer contemporary medical questions. The future of biomechanics is dependent on interdisciplinary research efforts and the education of tomorrow’s scientists

Upper limb function in children with cerebral palsy : range of motion, botulinum neurotoxin A and accelerometry metrics

Cerebral palsy (CP) is the most common cause of movement disorders in children and may result in diverse levels of severity of the disability, from very mild to very severe. The underlying neurological pathology in CP is by definition not progressive, but motor symptoms may cause permanent and progressive secondary movement complications, which often change over time. Movement disorders are a prominent component in individuals with CP and treatments are often aimed at affecting movement disorders. Since CP is caused by a permanent lesion to the brain, the lesion will affect the individual in different ways throughout life and in daily life activities. Thus, it is particularly important to understand how secondary complications develop from early childhood until adulthood in this population. Measurement tools that are evaluating individuals’ daily life need to be psychometrically evaluated, and we also need to evaluate the treatments outcome of the secondary complications within CP efficiently. Gaining more knowledge about secondary complications to CP is a priority in CP research. This thesis focuses on upper limb (UL) passive range of motion (pROM) and contracture development over time, botulinum neurotoxin A (BoNT-A) and on accelerometry based metrics evaluated in daily life in children and adolescents. Upper limb passive range of motion change over time and BoNT-A treatment were investigated by population-based data sourced from the Swedish national CP registry. Upper limb clinical assessments and accelerometry based metrics were obtained from 20 children and adolescents, who were residents of Sörmland or Västmanland in Sweden. Results show that one-third of children and adolescents with CP developed upper limb contractures and the pROM deteriorated over time. The contracture development started already at preschool age. The first and most severe contractures were found in wrist extension with extended fingers. Children with the most affected level of manual ability were at highest risk for contracture development. One-fifth of children with spastic or dyskinetic CP had been treated with BoNT-A in the ULs, 45% of them early at age, 1–3 years. Children with lower levels of manual ability or full pROM with resistance at the end of the movement range were most likely to receive a first UL BoNT-A treatment. At the first treatment occasion, thumb and forearm muscles were the most targeted. Interestingly, a first UL BoNT-A treatment at an early age, 1-3 years implied a favourable pROM development over time compared to children treated first time at a later age, 4-15 years. Early detection of a first sign of muscle shortening and thus early intervention before contractures are manifested can be one of the keys to successful outcomes. In daily life, during sedentary time and light-intensity physical activity, accelerometry metrics provide objective information about UL asymmetry and relative use. Thus, accelerometry metrics may provide complementary information to clinical assessments in daily life

Effect of a supination splint on upper limb function of cerebral palsy children after Botulinum Toxin A

Objective To investigate the effect a supination splint would have on upper limb function of cerebral palsy children for six months after receiving Botox® injections. Design Ten children attending weekly therapy enrolled in this prospective Quasi-experimental design where each child acted as his own control. Intervention was a supination splint and stretch massage. Assessment was based on pre- and post-intervention records of Modified Ashworth Scale, goniometry, Quality of Upper Extremity Skills Test (QUEST), and an independent panel assessment of videotaped records of hand function. Results Results show that spasticity declined in the forearm pronators, wrist flexors and thumb adductors. Active movement improved significantly in forearm supination and wrist extension. The QUEST demonstrated a significant change. Improvement in the hand function assessment was evident from the second month. Conclusion Findings support the premise that the supination splint is effective in improving upper limb function of cerebral palsy children after Botox® injections.Dissertation (M (Occupational Therapy))--University of Pretoria, 2007.Occupational TherapyM (Occupational Therapy)unrestricte

Studies of cerebral palsy in the childhood population of Edinburgh

This thesis is the result of an investigation of the prevalence, clinical findings and aetiology of cerebral palsy in the childhood population of Edinburgh which was carried out during 1952 and 1953, whilst the author held a George Guthrie Research Fellowship from the University of Edinburgh. The aims of the investigation were, firstly to establish the prevalence of cerebral palsy in the childhood population of the city; secondly to study the clinical features of cerebral palsy and their effects on the patient's way of life; to define some of the important aetiological factors in cerebral palsy in a representative group of children in the community. During the investigation it became increasingly apparent that the currently defined categories included in "Cerebral 'Palsy" did not allow for an accurate classification of cases by neurological findings. Eventually a new classification on the basis of neurological syndromes was evolved. This classification will be described and compared to previous classifications in Section 3. It was possible to establish figures for the prevalence of cerebral palsy in the childhood population of Edinburgh, though a complete ascertainment of all patients was not made. The clinical features of cerebral palsy in the childhood ;community were studied and are described in Section 4. During the survey it became increasingly apparent that "Cerebral Palsy" was no clinical entity. Rather it comprised a number of neurological disorders in which the only common factor appeared to be that there was motor dysfunction due to abnormality of the brain which was present in early life. The clinical features varied widely from category to category. The ways in which patients were handicapped and the extent to which they were printed from taking part in everyday activities were very different. A detailed study was made of the clinical findings and handicaps of patients and they were compared to those described by previous authors. Thus, some idea of the importance of cerebral palsy in the community was obtained, (Section 5). Aetiological factors which were important in one form of cerebral palsy were found to be much less important in others. Many different "causes" of cerebral palsy were found which varied from developmental malformation to traumatic head injury, and from abnormal parturition to the complications of infectious diseases in early life. The multiplicity of aetiological factors in single categories and even single patients was impressive. For example, within the category of "Ataxic Diplegia" patients were found whose disorder appeared to be genetically determined, and patients who were suffering from the effects of birth injury, parainfectious encephalomylitis or meningitis. To take account of the multiplicity of aetiological factors it was necessary to study the heredity and social backgrounds of patients as well as their individual' birth and later histories. The current concept of cerebral palsy as being due predominantly to the effects of birth injury is a misleading simplification of the true position. In the same way as there are many different causes of stillbirth and infant death, !so there are many causes of cerebral palsy in children who survive. The later sections of this thesis are concerned with demonstrating that the aetiological factors in cerebral palsy are as complex as those involved in infant mortality. Social, genetic, obstetric and many unknown factors play a .part. An attempt has been made to define the importance of some of them in Sections 5 and 6

Muscle composition, reach, physical activity and botulinum toxin treatment in children with cerebral palsy

Cerebral palsy (CP), the most common cause of movement disorders and physical disability in children all over the world, is caused by an injury to the developing brain. Although this injury is not progressive, the manifestations of the disorder change as the child ages. Spasticity and altered viscoelastic properties of the muscle often enhance muscle resistance to stretch and the peak spasticity of the calf muscles in children with CP observed at four years of age declines thereafter until twelve years of age. The cause of muscle contractures, which appear early and progress throughout childhood and adolescence is unclear and needs to be elucidated further to help design more effective preventive measures. Therefore, the first aim of this thesis was to further characterize muscle pathophysiology in children with CP with fixed contractures. Treatment of patients with CP involves a wide variety of efforts. Standardized and objective follow-up, as well as cost effectiveness are of considerable importance. Therefore, the second aim here focused on novel tools for clinical evaluation, as well as assessment of the economics of switching between two botulinum toxins (BoNT-A) in treatment of children with CP. We developed further a three-dimensional test of arm reach in typically developing (TD) children and tested the feasibility of this test in young adults with CP. We also developed a new approach evaluating the effects of BoNT-A treatment involving monitoring the child ́s home and school environments with four accelerometers. Moreover, we made a controlled switch from one brand of BoNT-A to another in attempt to reduce the drug cost without reducing efficacy or duration or exacerbating side-effects. The major novel findings with respect to muscle pathophysiology are that impaired production of ribosomes probably explains, at least in part, the deficient growth of skeletal muscle observed in children with CP and that levels of pro-inflammatory cytokines are elevated in their muscles. The latter alteration contributes to both inhibition of growth and expansion of the extracellular matrix and perhaps to the development of muscle contractures as well in children with CP. In addition, in the muscles of these children the number of satellite cells was reduced, the amount of intramuscular collagen situated around bundles of muscle fibers elevated and expression of the fatigable and fast Myosin Heavy Chain IIx isoform in wrist flexors higher in comparison to TD children. The major findings with respect to the development of novel tools for assessment and cost- effectiveness are that the 3D Reach Test for the arms exhibits excellent inter- and intra- session reliability in TD children, as well as excellent feasibility and reliability in a pilot study on young adults with CP. Moreover, monitoring children with CP in their own environment with four accelerometers following BoNT-A treatment reveals previously unknown effects on physical activity, effects not detected by routine clinical follow-up, such as a decline in ambulatory activity after injection into the legs. When the BoNT-A preparation used previously was replaced by another commercial BoNT-A product, the parents reported the treatment of their children with CP to be equally effective, while the cost was 41% lower with few, similar and transient side-effects. In conclusion, the present investigations provide new information on the pathophysiology of muscle in children with cerebral palsy that can help improve our understanding of contracture formation. The 3D Reach Test and post treatment monitoring with accelerometers are promising new tools for evaluation of the effects of treatment on reach and everyday movement. The cost of BoNT-A treatment can be reduced considerably by switching to another brand without compromising either the effect or patient safety

The Contributions of Extracellular Matrix and Sarcomere Properties to Passive Muscle Stiffness in Cerebral Palsy

Cerebral palsy results from an upper motor neuron lesion and significantly affects skeletal muscle stiffness. The increased stiffness that occurs is partly a result of changes in the microstructural components of muscle. In particular, alterations in extracellular matrix, sarcomere length, fibre diameter, and fat content have been reported; however, experimental studies have shown wide variability in the degree of alteration. Many studies have reported changes in the extracellular matrix, while others have reported no differences. A consistent finding is increased sarcomere length in cerebral palsy affected muscle. Often many components are altered simultaneously, making it difficult to determine the individual effects on muscle stiffness. In this study, we use a three dimensional modelling approach to isolate individual effects of microstructural alterations typically occurring due to cerebral palsy on whole muscle behaviour; in particular, the effects of extracellular matrix volume fraction, stiffness, and sarcomere length. Causation between the changes to the microstructure and the overall muscle response is difficult to determine experimentally, since components of muscle cannot be manipulated individually; however, utilising a modelling approach allows greater control over each factor. We find that extracellular matrix volume fraction has the largest effect on whole muscle stiffness and mitigates effects from sarcomere length

Extracellular vesicle characteristics and micro RNA content in cerebral palsy and typically developed individuals at rest and in response to aerobic exercise.

In this study, the properties of circulating extracellular vesicles (EVs) were examined in cerebral palsy (CP) and typically developed (TD) individuals at rest and after aerobic exercise, focusing on the size, concentration, and microRNA cargo of EVs. Nine adult individuals with CP performed a single exercise bout consisting of 45 min of Frame Running, and TD participants completed either 45 min of cycling (n = 10; TD EX) or were enrolled as controls with no exercise (n = 10; TD CON). Blood was drawn before and 30 min after exercise and analyzed for EV concentration, size, and microRNA content. The size of EVs was similar in CP vs. TD, and exercise had no effect. Individuals with CP had an overall lower concentration (~25%, p \u3c 0.05) of EVs. At baseline, let-7a, let-7b and let-7e were downregulated in individuals with CP compared to TD (p \u3c 0.05), while miR-100 expression was higher, and miR-877 and miR-4433 lower in CP compared to TD after exercise (p \u3c 0.05). Interestingly, miR-486 was upregulated ~2-fold in the EVs of CP vs. TD both at baseline and after exercise. We then performed an in silico analysis of miR-486 targets and identified the satellite cell stemness factor Pax7 as a target of miR-486. C2C12 myoblasts were cultured with a miR-486 mimetic and RNA-sequencing was performed. Gene enrichment analysis revealed that several genes involved in sarcomerogenesis and extracellular matrix (ECM) were downregulated. Our data suggest that circulating miR-486 transported by EVs is elevated in individuals with CP and that miR-486 alters the transcriptome of myoblasts affecting both ECM- and sarcomerogenesis-related genes, providing a link to the skeletal muscle alterations observed in individuals with C