HOT TOPICS IN CEREBRAL PALSY: MUSCLE RESEARCH FORUM

Transcription

1 Australasian Cerebral Palsy Clinical Trials Network (AusCP-CTN) Centre for Research Excellence (CRE) HOT TOPICS IN CEREBRAL PALSY: MUSCLE RESEARCH FORUM 30 NOVEMBER 2018 RESEARCH TEAM AusCP-CTN CRE Chief Investigators Prof. Roslyn Boyd, Prof. Iona Novak, Prof. Euan Wallace, Prof. Nadia Badawi, A/Prof. Michael Fahey, Prof. Stephen Rose, Prof. Paul Colditz, Prof. Jenny Ziviani, Prof. Catherine Elliott, Prof. Susan Stott. AusCP-CTN CRE Associate Investigators Dr Lee Barber, Prof. Peter Davies, A/Prof. Andrea Guzzetta, Dr Sarah McIntyre, Dr Leanne Sakzewski, A/Prof. Anthony Smith, Prof. Robert Ware, Dr Koa Whittingham, A/Prof. Ray Russo. CONTACT E: W: GET INVOLVED Become a member of The Australasian Cerebral Palsy Clinical Trials Network. To join, visit: W: 1

2 Australasian Cerebral Palsy Clinical Trials Network Centre for Research Excellence PROGRAM Hot Topics in Cerebral Palsy: Muscle Research Forum 30 November :00am 5:30pm Centre for Children's Health Research 62 Graham St South Brisbane QLD 4101 SPEAKERS Prof. Richard Lieber A/Prof. Glen Lichtwark Prof. Ros Boyd Dr Steven Obst Prof. David Lloyd Prof. Andy Cresswell Prof. Susan Stott Dr Lee Barber A/Prof. Jane Valentine Dr Christopher Carty

3 CHAIRS Professor Roslyn Boyd Chief Investigator and Director of the CRE, QLD Lead, Chair of the Clinical Trials theme and a member of the Early Detection and Neuroimaging theme; Scientific Director of the Queensland Cerebral Palsy Rehabilitation & Research Centre, Faculty of Medicine, The University of Queensland. NHMRC Research Fellow. Professor Boyd leads an internationally recognised team of researchers conducting clinical trials of novel interventions geared to optimising neuroplasticity, early detection of cerebral palsy, longitudinal comprehensive outcomes linked to brain structure and function. Her team has conducted 17 RCTs in CP and infants born preterm. She has received >$36M in grants including 13 NHMRC, 1ARC, 1 NIH and has published >275 publications. She has had continuous NHMRC people support, being a Research Fellow ( ) and previous QLD Smart State Fellow. She and her research team have been awarded the most prestigious international prize for CP Research, the Gayle Arnold Award, in 2010, 2011 and Recently she received the Mentorship Award from The American Academy for Cerebral Palsy and Developmental Medicine and the Faculty of Medicine at the University of Queensland. Professor Rick Leiber Professor & Chief Scientific Officer, Shirley Ryan Ability Lab & Departments of Physical Medicine & Rehabilitation & Biomedical Engineering. Northwestern University, Chicago. Professor Lieber s work is characterised by its interdisciplinary nature an approach that is relevant to those who study biomechanics and Orthopaedic Surgery. He has published over 250 articles in journals ranging from the very basic such as The Biophysical Journal and The Journal of Cell Biology to those more applied such as The Journal of Hand Surgery and Clinical Orthopaedics and Related Research. Professor Lieber s research focuses on design and plasticity of skeletal muscle. Currently, he is developing state-of-the-art approaches to understanding muscle contractures that result from cerebral palsy, stroke and spinal cord injury. 3

4 Professor Sue Stott Professor of Paediatric Orthopaedic Surgery, University of Auckland, NZ Clinical Director, Department of Paediatric Orthopaedics, Starship Children s Hospital, NZ CRE Chief Investigator, New Zealand lead, a member of the Clinical Trials Theme and Chair of the New Zealand CP Register Professor Ngaire (Sue) Stott has a personal chair at the University of Auckland and is Professor of Paediatric Orthopaedic Surgery. She is also a practising paediatric orthopaedic surgeon and is Service Clinical Director for Starship Children s Hospital Paediatric Orthopaedic Department and Chair of the NZ Cerebral Palsy Register Governance Group. Starship Childrens Hospital is the only stand-alone paediatric hospital in New Zealand and acts as a tertiary and quaternary referral centre for children with cerebral palsy. She therefore has the ability to translate key research findings into clinical practice through strong alliances with key stake-holders within the health sector. In terms of general citation indices, her work has been cited 1546 times. She has received the Gillies medal from the NZ Orthopaedic Assoc. for best paediatric orthopaedic research paper in 1998 and Associate Professor Jane Valentine Head of Department and Clinical Lead of Paediatric Rehabilitation, Princess Margaret Hospital for Children Western Australia Associate Professor, University of Western Australia, School of Paediatrics and Child Health Member of the Clinician network and the Clinical Trials, and Knowledge Translation and Implementation, themes for the CRE. Associate Professor Jane Valentine is a Paediatric Rehabilitation physician and Head of the Kids Rehab Department at Perth Children s Hospital WA. Kids Rehab WA is a clinically integrated research unit and have an established research program in the area of the long term outcomes of botulinum toxin use in children and adolescents with Cerebral Palsy. 4

5 INTERNATIONAL KEYNOTE SPEAKER Professor Rick Leiber Professor & Chief Scientific Officer, Shirley Ryan Ability Lab & Departments of Physical Medicine & Rehabilitation & Biomedical Engineering. Northwestern University, Chicago. Professor Lieber s work is characterised by its interdisciplinary nature an approach that is relevant to those who study biomechanics and Orthopaedic Surgery. He has published over 250 articles in journals ranging from the very basic such as The Biophysical Journal and The Journal of Cell Biology to those more applied such as The Journal of Hand Surgery and Clinical Orthopaedics and Related Research. Professor Lieber s research focuses on design and plasticity of skeletal muscle. Currently, he is developing state-of-the-art approaches to understanding muscle contractures that result from cerebral palsy, stroke and spinal cord injury. ABSTRACTS 1. Biological & Biomechanical Studies of Skeletal Muscle Contractures in Cerebral Palsy. Skeletal muscle is a highly plastic tissue, responding both to level of use and amount of neural input. After cerebral palsy (CP) altered neural input can result in muscle contractures. We have studied the mechanics and biology of muscle from children with wrist flexion contractures secondary to CP. Dramatic architectural changes are observed in these children whereby sarcomere lengths are dramatically altered relative to patients without upper motor neuron lesions. This suggests dramatic alterations in the regulation of muscle growth in these children. Biomechanical studies of isolated single muscle cells reveal an increased passive modulus and decreased resting sarcomere length suggesting alterations in the cellular cytoskeleton. Gene expression profiling reveals a number of conflicting biological pathways in spastic muscle. Specifically, this muscle adapts by altering processes related to extracellular matrix production, fiber type determination, fiber hypertrophy and myogenesis. These transcriptional adaptations are not characteristic of muscle adaptations observed in Duchenne muscular dystrophy or limb immobilization. Superimposed upon the dramatic biological & structural adaptations is a loss in the number of satellite cells that are located throughout the muscle. Even the remaining satellite cells have epigenetic changes that can dramatically influence our ability to rehabilitate these muscles. Recent data shows that several anti-cancer drugs are able to reverse these epigenetic changes, thus rescuing the satellite cells and promoting myogenesis. Taken together, these results support the notion that, while contracture formation is multifactorial and neural in origin, significant structural alterations in muscle also occur. An understanding of the specific changes that occur in the muscle and extracellular matrix may facilitate the development of new conservative or surgical therapies for this devastating problem. 2. Clinically relevant skeletal muscle anatomy and physiology In this lecture, the basic anatomical and physiological properties of skeletal muscle will be reviewed with special emphasis to cerebral palsy. The active and passive mechanical properties as well as high resolution muscle structural components will be reviewed. 5

6 INVITED NATIONAL SPEAKERS Professor David Lloyd Professor of Biomechanical Engineering, School of Allied Health Sciences, Griffith University Director, Gold Coast Centre for Orthopaedic Research, Engineering and Education (GCORE), Menzies Health Institute, Queensland. David Lloyd is a Professor of Biomechanical Engineering in the School of Allied Health Sciences and director of the Gold Coast Centre for Orthopaedic Research, Engineering and Education (GCORE) in the Menzies Health Institute Queensland. GCORE is an alliance between Griffith University, the Gold Coast University Hospital and other Gold Coast and in Brisbane hospitals. David was also co-founder of, and a Professor in, Griffith s new Advanced Design and Prototyping Technologies Institute (ADaPT), leading the medical devices group. He is a mechanical engineer who first worked in the aeronautical industry, but then completed a PhD and post-doctoral training in biomechanical engineering and neurophysiology. After a long career in biomechanical engineering he is now an elected Fellow of the International Society of Biomechanics. David and team have developed computer-simulation methods to study the causes, prevention and rehabilitation of neuromusculoskeletal conditions, with these methods now being adopted in the orthopaedics and neurorehabilitation industries. David and team are currently developing accurate personalised digital models of humans with real-time capabilities by combining data from laboratory-based instrumentation, multimodal medical imaging and wireless wearable devices. David and team work with hospitals, and sporting organisations, and medical imaging, orthopaedic, and wearable device companies. He has more than 200 scientific journal papers, over 11,700 citations and a H index of 54 (Google Scholar). David has attracted over $AUD23Million in R&D funding. ABSTRACT Assistive wearable devices for rehabilitation for children with disability The nervous system and musculoskeletal tissues will repair or degrade based upon their functional neurophysiological and mechanobiological niches. These niches are the result of personalised and functionally consistent efferent and afferent neural excitation, motion and loading (i.e. tissue strains), and the musculoskeletal tissues' biology and morphology. To repair musculoskeletal tissues the "ideal" in vivo tissue strains can be potentially attained by the patient using real-time afferent biofeedback and/or movement assistance during rehabilitation. Nervous system rehabilitation requires the patient to perform desired rehabilitation movements that is coupled with appropriate and consistent muscle excitation (e.g. functional electrical stimulation) and afferent biofeedback. In both rehabilitation scenarios, movement assistance, muscle excitation and/or afferent biofeedback can be achieved via innovative and personalised wearable devices that are enabled by personalised digital twins of the patient. Personalised digital twins are multiscale neuromusculoskeletal rigid body and finite element models, and/or their AI equivalent models that can operate in real-time. This talk will examine how this can be achieved, with examples. 6

7 Professor Sue Stott Professor of Paediatric Orthopaedic Surgery, University of Auckland, NZ Clinical Director, Department of Paediatric Orthopaedics, Starship Children s Hospital, NZ CRE Chief Investigator, New Zealand lead, a member of the Clinical Trials Theme and Chair of the New Zealand CP Register Professor Ngaire (Sue) Stott has a personal chair at the University of Auckland and is Professor of Paediatric Orthopaedic Surgery. She is also a practising paediatric orthopaedic surgeon, Service Clinical Director for Starship Children s Hospital Paediatric Orthopaedic Department, and Chair of the NZ Cerebral Palsy Register Governance Group. Starship Children's Hospital is the only stand-alone paediatric hospital in New Zealand and acts as a tertiary and quaternary referral centre for children with cerebral palsy. She therefore has the ability to translate key research findings into clinical practice through strong alliances with key stake-holders within the health sector. In terms of general citation indices, her work has been cited 1546 times. She has received the Gillies medal from the NZ Orthopaedic Assoc. for best paediatric orthopaedic research paper in 1998 and ABSTRACT MRI of muscle in healthy children and children with CP Premature declines in function among individuals with CP may occur as a result of reduced and early declining musculoskeletal health, reduced strength and anaerobic reserve, beyond that which is expected for typically-developed peers. Emerging MRI evidence has revealed altered muscle growth and quality during early development and into adulthood among individuals with CP, thus placing them at heightened risk of frailty and chronic multi-morbidity. This talk will highlight recent research in the area and de-bunk the notion that all muscles are created equal. 7

8 Associate Professor Jane Valentine Head of Department and Clinical Lead of Paediatric Rehabilitation, Princess Margaret Hospital for Children Western Australia Associate Professor, University of Western Australia, School of Paediatrics and Child Health Member of the Clinician network and the Clinical Trials, and Knowledge Translation and Implementation, themes for the CRE. Associate Professor Jane Valentine is a Paediatric Rehabilitation physician and Head of the Kids Rehab Department at Perth Children s Hospital WA. Kids Rehab WA is a clinically integrated research unit and have an established research program in the area of the long term outcomes of botulinum toxin use in children and adolescents with Cerebral Palsy. ABSTRACT Impact of botulinum toxin A on muscle in children with CP Botulinum Toxin (BoNTA) is standard care for the management of hypertonia in children with CP and is graded an effective evidence based treatment. The short-term outcomes are well documented and when used within an integrated approach and started at a young age, BoNTA has the potential to improve overall function of children with CP. However, there is limited evidence on the outcome of repeated injections over time and recent publications have raised concern regarding the longterm effect of BoNTA on muscle size and morphology in children with CP. The evidence for and role of repeat use of BoNTA and the effect of BoNTA on muscle volume and structure in both animal and humans will be discussed. 8

9 INVITED CRE SPEAKERS Dr Lee Barber Senior Lecturer and Head of Course - Physiotherapy, Central Queensland University Honorary Research Fellow, Child Heath Research Centre, University of Queensland and Advance Queensland Research Fellow in muscle mechanics, gait analysis and functional capacity in individuals with cerebral palsy Dr Lee Barber is Head of Course - Physiotherapy, CQUniversity and an Advance Queensland Research Fellow in muscle mechanics, gait analysis and functional capacity in individuals with cerebral palsy (CP). Dr Barber has more than 10 years of clinical experience as a physiotherapist, with 32 publications (>600 citations) and over 50 national and international conference presentations. Dr Barber has received >$4.0M in national and >$100K in international research funding. He is an early career researcher within the Australasian Cerebral Palsy Clinical Trials Network for early detection and optimising effective interventions for children with cerebral palsy. His expertise is in muscle morphology and mechanics in children and adults with CP, including freehand 3D ultrasound, 3D motion capture, surface EMG and dynamometry to measure in-vivo muscle structure and function. This important data has been incorporated into patient specific musculoskeletal biomechanical models which may potentially allow orthopaedic surgeons to perform virtual surgery. Dr Barber also investigates the efficacy of exercise interventions to improve muscle health and functional capacity in individuals with CP and uses accelerometry and GPS to study habitual physical activity in this group. Dr Barber develops clinical tools to measure muscle mechanics and investigate how treatments for spastic type CP impacts muscle growth, structure and function and an individual s capacity to perform activities of daily living. Dr Steven Obst Senior Lecturer Physiotherapy, School of Health, Medical and Applied Sciences, Central Queensland University Honorary Research Fellow, Child Heath Research Centre, University of Queensland Adjunct Senior Lecturer, School of Allied Health Sciences, Griffith University Dr Obst is a Senior Lecturer in musculoskeletal physiotherapy and early career researcher specialising in muscle and tendon imaging, injury and rehabilitation. He has over 10 years of clinical experience in musculoskeletal physiotherapy and tertiary level teaching, holds bachelor degrees in Physiotherapy, Exercise Science and Human Movement Science, and a received a PhD in Applied Biomechanics from Griffith University in He currently has 19 publications, 200+ citations and has received >$160K in funding. His research focuses on novel applications of 3D ultrasound to assess muscle and tendon structure, function and adaptation in young adults, and has recently applied these methods to examine muscle size and structure in children with cerebral palsy. Prior to commencing at CQUniversity Dr Obst was employed as a post-doctoral research fellow at the Queensland Cerebral Palsy and Rehabilitation Research Centre (The University of Queensland) under the supervision of Professor Roslyn Boyd and Dr Lee Barber and was responsible for the collection and analysis of musculoskeletal medical imaging, 3D gait analysis and physiotherapy functional capacity assessments in children aged 8-10 years with cerebral palsy. Dr Obst maintains 9

10 an Honorary Research Fellow appointment within the UQ Child Health Research Centre and Adjunct Senior Lecturer within the School of Allied Health Sciences, Griffith University. SHARED ABSTRACT Muscle growth and quality in individuals with CP Lower limb muscle growth, size and quality is important for force generation, walking ability and muscle health. In children with cerebral palsy muscle adaptations include reduced size and altered proportions of contractile and non-contractile tissue which contribute to muscle weakness, stiffness and altered metabolic function. Intervention studies in individuals with cerebral palsy can alter muscular properties for improved function and health. A review of current research findings in cerebral palsy impaired muscle growth and development of muscle will be presented. 10

11 Associate Professor Glen Lichtwark School of Human Movement and Nutrition Sciences, Faculty of Health and Behavioural Sciences, The University of Queensland Glen Lichtwark is an Associate Professor in the School of Human Movement Studies at The University of Queensland. He was awarded his PhD in 2005 from University College London (UK), where he studied the influence of muscle and tendon elasticity on power output and energetics of muscle. He has subsequently worked as a postdoctoral fellow at the Royal Veterinary College (UK), Imperial College (UK) and more recently at Griffith University ( ). Glen is particularly interested in how elasticity in muscles and tendons in the lower leg and foot influence the function of these muscles and what impact this has on the ability to generate force or perform controlled movements. ABSTRACT Mechanics and control of calf muscles during walking with cerebral palsy There are numerous musculoskeletal adaptations which occur secondary to the neural lesion which causes cerebral palsy (CP). These can present as muscle weakness, increased muscle stiffness or contracture and variations in skeletal alignment. However, it is hard to partition the effect of each of these characteristics on gait patterns that are typically seen in CP (e.g. equinus or crouch gait). Here I will present some data on the kinematic and kinetic function of calf muscles (gastrocnemius and soleus) in children with CP compared to typically developing children and postulate on the root causes of gait patterns seen in children with CP. Some computer simulation approaches to explore these problems will also be introduced. 11

12 Professor Andy Cresswell Head, School of Human Movement and Nutrition Sciences Faculty of Health and Behavioural Sciences, The University of Queensland Andrew is Head of the School of Human Movement and Nutrition Sciences at The University of Queensland and Professor in Biomechanics/ Neurophysiology. Andrew completed his medical doctorate in Neuroscience from the Karolinska Institute, Sweden, in 1993 and returned to Australia in 2005 as Professor in Biomechanics/Neurophysiology at UQ. Andrew s research interest is in the integration of neurophysiology and biomechanics to investigate the control of human movement. He is past President of the International Society of Biomechanics, a Fellow of Sports Medicine Australia and a past President of the Australian and New Zealand Society of Biomechanics. ABSTRACT Use and misuse of EMG Clinical gait analysis is commonly used in the evaluation and treatment of children with cerebral palsy (CP). While the repeatability of kinematic and kinetic measures of gait has previously been evaluated, the repeatability of electromyography (EMG) recordings or measures calculated from EMG remains unclear. Moreover, the relationship between EMG and kinematic or kinetic parameters is blurred. This talk will highlight research utilising EMG in the evaluation of children with CP and attempt to identify potential pitfalls. 12

13 Dr Christopher Carty Clinical Research Manager (Orthopaedics), Children's Health Queensland Hospital and Health Service Dr Chris Carty is an exercise physiologist appointed as Clinical Motion Analysis Consultant in the Queensland Children s Motion Analysis Services (Children s Health Queensland) and an Advance Queensland Innovation Fellow at Griffith University. His current research interests include computational simulations and predictive modelling to inform paediatric deformity correction surgery. Dr Carty attained a Bachelor of Applied Science (Human Movement Studies) in 2003 from the University of Queensland and a PhD in Orthopaedic Biomechanics in 2009 from the University of Queensland. In 2018 Dr Carty was awarded a Churchill Fellowship to explore 3D printing solutions for the treatment of children with bony deformities. He has published over 40 papers related to biomechanics across the lifespan. ABSTRACT Personalised neuromusculoskeletal modelling for CP gait Clinical gait analysis methods have barely changed over the past few decades and therefore many questions relating to gait dysfunction in CP remain unanswered. In recent years, user-friendly musculoskeletal modelling software (e.g. OpenSim) has enabled calculation of muscle-tendon lengths, muscle moment arms, muscle forces and joint contact forces. The talk will discuss the benefits and challenges in adopting a new simulation framework in clinical gait analysis with a focus on CP gait. 13

14 Acknowledgements AusCP-CTN CRE Chief Investigators: Prof. Roslyn Boyd, Prof. Iona Novak, Prof. Euan Wallace, Prof. Nadia Badawi, A/Prof. Michael Fahey, Prof. Stephen Rose, Prof. Paul Colditz, Prof. Jenny Ziviani, Prof. Catherine Elliott, Prof. Susan Stott. AusCP-CTN CRE Associate Investigators: A/Prof. Andrea Guzzetta, Dr Sarah McIntyre, Dr Leanne Sakzewski, A/Prof. Anthony Smith, Prof. Robert Ware, Dr Koa Whittingham, A/Prof. Ray Russo, Dr Lee Barber, Prof. Peter Davies. Queensland Cerebral Palsy and Rehabilitation Research Centre team: Prof. Roslyn Boyd, A/Prof. Karen Barlow, Dr Priya Edwards, Dr Susan Sullivan, Dr Anna MacDonald, Dr Annie Chen, Dr Mark Bowles, Dr Lee Barber, Dr Leanne Sakzewski, Dr Koa Whittingham, Dr Kath Benfer, Dr Joanne George, Dr Steve Obst, Dr Lisa Copeland, Dr Kristie Bell, Dr Chris Carty, Dr Tracey Evans, Dr Corrine Dickinson, Dr Ashleigh Wright, Ms Christine Finn, Ms Kym Morris, Ms Bernadette Shannon, Ms Camilla Davenport, Ms Debra Khan, Ms Carly Dickinson, Ms Sarah Goodman, Ms Rebecca Caesar, Mr Jarred Gillett, Mr Miles Seidel, Dr Catherine Mak, Ms Sarah Reedman, Ms Felicity Read, Ms Jane Wotherspoon, Ms Andrea Burgess, Ms Ellen Armstrong, Mr Noah Betar, Ms Denni Purcell, Mr Julien Savina, Ms Elyanna Fong. 14