Lower Limb Strength Training for Children with Spastic Diplegic

Transcription

Lower Limb Strength Training for Children
with Spastic Diplegic Cerebral Palsy
receiving Botulinum Neurotoxin Type-A:
Outcome Evaluations at all levels of the
International Classification of Functioning,
Disability and Health.
SÎAN ANDREA WILLIAMS BSc (HONS)
THIS THESIS IS PRESENTED FOR THE DEGREE OF DOCTOR OF PHILOSOPHY
THE UNIVERSITY OF WESTERN AUSTRALIA
SCHOOL OF SPORT SCIENCE, EXERCISE AND HEALTH
THIS RESEARCH WAS CONDUCTED IN CONJUNCTION WITH THE DEPARTMENT OF PEDIATRIC
REHABILITATION, AND THE DEPARTMENT OF DIAGNOSITC IMAGING AT PRINCESS MARGARET HOSPITAL
FOR CHILDREN.
2012
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DECLARATION FOR THESES CONTAINING PUBLISHED WORK AND/OR WORK PREPARED FOR
PUBLICATION
This thesis contains published work and/or work prepared for publication, some of which has
been co-authored. The bibliographical details of the work are presented for each paper. The
work involved in designing the studies described in this thesis was performed primarily by Sîan
Williams (candidate). The thesis outline and experimental design was planned and developed
by the candidate, in consultation from Dr Siobhan Reid, Dr Catherine Elliott, and Dr Eve Blair
(the candidates Academic supervisors), and with contributions from Dr Jane Valentine, Dr
Anna Gubbay and Miss Nadine Williams. All participant recruitment and management was
carried out by the candidate. In addition, the candidate was responsible for all data analysis.
The candidate drafted the original thesis, with Dr Siobhan Reid, Dr Catherine Elliott, Dr Jane
Valentine, Dr Eve Blair, Dr Anna Gubbay and Miss Nadine Williams providing feedback on
drafts until the examinable version was finalised.
Student Signature:
Coordinating Supervisor Signature:
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ABSTRACT
Cerebral Palsy (CP) is one of the most common childhood physical disabilities in the world1.
The associated impairments of CP often encompass all components of functioning. Spasticity
and muscle weakness are two major motor impairments associated with CP. Botulinum
Neurotoxin Type-A (BoNT-A) is a common treatment for spasticity management with many
reported functional benefits; however muscle weakness and muscle atrophy have been linked
with BoNT-A treatment. Children with CP are already predisposed to decrements in muscle
strength and size, therefore any treatment potentially leading to further weakening and
atrophy of the muscle should be well understood.
This doctorate is written as a series of papers each adding to the understanding of the effects
of BoNT-A and strength training in children with CP. The opening paper presented in this thesis
is the first known documentation of the morphological alterations of spastic muscle to BoNT-A,
alongside information on alterations in muscle strength and functional ability. Ten boys and
five girls with spastic diplegia, aged 5-12 years and classified as Gross Motor Function
Classification System (GMFCS) level I-II were recruited from the Cerebral Palsy Mobility Service
in Perth, Australia, and were assessed before and (approximately 5weeks) after BoNT-A.
Outcome measures included isometric dynamometry assessing muscle strength, Magnetic
Resonance Imaging (MRI) to measure muscle volume, and the Timed-Up and Go (TUG) test and
the 6-Minute Walk Test (6MWT) to assess functional walking capacity. This paper uncovered
documented muscle atrophy in BoNT-A injected muscles and hypertrophy of synergist
muscles. However, atrophy of the injected muscle was relatively minor compared to evidence
provided in animal studies and appeared to have no negative impact on muscle function.
Given that the single treatment of BoNT-A did have an effect on muscle morphology, a logical
progression of treatment planning would be to combine both BoNT-A treatment (for spasticity
management) and strength training (for muscular weakness) to target both impairments
simultaneously. The second, third and fourth paper of this thesis aim to provide a
comprehensive overview of the combined effect of BoNT-A treatment and a home based
strength training intervention. A secondary aim of this thesis is to determine the best practice
in terms of timing of application of a strength training intervention in relation to reception of
BoNT-A for children with CP. The International Classification of Functioning, Disability and
Health (ICF) is utilised by health professionals as best practice for a holistic approach to the
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management of people with disabilities, and is applied throughout this thesis to assess
outcomes of the combined interventions of BoNT-A and strength training.
The study design, dictated by current clinical care, utilised a repeated measures crosscomparison design. The fifteen children (aged 5-12 years, GMFCS I-II) recruited in this study
completed four assessments over 6months timed around receipt of BoNT-A treatment.
Children in the study were block randomised by age, gender and GMFCS level into either a PRE
or POST BoNT-A strength training group. The PRE group completed home-based strength
training in the 12 weeks prior to injection, and the POST group completed the training
following injection. A control group of eight children also completed a 6month preintervention baseline phase, with equivalent assessment time points scheduled around their
BoNT-A treatment.
Paper two addressed alterations at the level of impairment of the ICF, with assessments
including isometric and isokinetic dynamometry for muscle strength, spasticity, selective
motor control and muscle volume. It also incorporated the Goal Attainment Scale (GAS) which
assessed attainment of individual functional goals. Paper two demonstrated that the
combination of BoNT-A and strength training was successful in spasticity reduction, improving
strength and achieving functional goals, over and above treatment with BoNT-A alone. Neither
training in the PRE or POST group resulted in a superior improvement compared to the other.
However, the POST group consistently displayed a greater capacity for changes of strength in
the immediate (10 week) response to strength training, whilst the PRE group consistently
displayed greater changes at 6months.
Paper three addressed further changes at the impairment level and included threedimensional gait analysis to assess outcomes of walking gait (the Gait Deviation Index, GDI,
and kinetic joint power profiles). This paper demonstrated that the impact of the combined
therapy on walking gait was positive, revealing a resulting gait closer to that of typically
developing gait, whilst indicating a more efficient use of muscle energy transfer to drive
forward locomotion. The POST group demonstrated greater improvements in the GDI, but
there was no difference from timing of strength training on the effect of power generation or
absorption at the hip, knee or ankle joints.
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Paper four evaluated the effect of the combined therapy at the activity, participation and
quality of life (QoL) dimensions of the ICF. At the activity dimension of the ICF, outcome
measures included the TUG and the 6MWT. At the participation dimension of the ICF, The
Assessment of Life Habits (LIFE-H), measured difficulties in participation in life habits, and
Canadian Occupational Performance Measure (COPM) were included. To assess contextual
factors of the ICF, The Cerebral Palsy Quality of Life Questionnaire for Children assessed quality
of life (QoL). This paper suggests that the combined therapies had a positive impact on activity,
participation and QoL, with improvements in the TUG, and some domains of participation and
QoL. There was no differential effect of timing on activity, participation and QoL, with the
exception of family health, and emotional well-being and self esteem of the child in favour of
the PRE group.
Small morphologic alterations were established in injected and synergistic muscles, and
indicated the need for BoNT-A treatment to be combined with a muscle strengthening
intervention for improved outcomes in children with CP. This research has demonstrated
successful outcomes of applying home based strength training in combination with BoNT-A
injections at all levels of the ICF. Either delivered PRE or POST BoNT-A treatment, strength
training may be individually adapted to suit the needs of the child to improve clinical
outcomes. CP management is a lifelong challenge that requires clinicians to consider, and
treat, the impairments affecting the child holistically. The outcome of this research has
significant implications for the prescription of strength training and BoNT-A therapy in the CP
population.
REFERENCE
1.
Paneth N, Hong T, Korzeniewski S. The descriptive epidemiology of cerebral palsy. Clin
Perinatol. 2006;33:251-67.
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ACKNOWLEDGEMENTS
I have been fortunate enough to have the most amazing support and encouragement from so
many people in my life through these past four years. I know that these acknowledgments
cannot do my gratitude justice.
To my (team) of supervisors, you have been patient teachers and constant cheerleaders over
the years, and I am so lucky to have had each of you providing me guidance. Si, I don’t even
know where to begin. You have dedicated so much of your time and energy to me and this
study, I can’t possibly imagine having done this without you and your support. It has meant so
much to be able to work with someone like you who has held my hand the whole way through.
Cath, thank you for your time, effort, patience and particularly for the support you gave me
through the more challenging aspects of this study. You guided me through this clinical study,
a domain of which I had no prior experience in. Jane, I am so grateful for your feedback and
persistent interest in my work. Your expertise and support has been a huge motivation, thank
you for pushing me and challenging me. Eve, it was a privilege to have you on board, thank you
so much for all of your insight, feedback and assistance in the development and writing up of
this study. Nadine and Anna, thanks to each of you for your help in the development of this
complex study, and sharing your areas of expertise to strengthen it.
To those involved at Princess Margaret Hospital, at The Department of Paediatric
Rehabilitation and the Department of Diagnostic Imaging. Thank you for your time, support
and feedback, particularly throughout the planning and incredibly demanding data collection
stage of this study. It took the cooperation and understanding of so many of you to make the
complex timing of assessments achievable. Tania Shillington, we made it through some crazy
months of data collection, and I thank you so much for everything. You made every one of
those sessions possible and enjoyable.
To the sixteen children and families involved in this study; I am eternally grateful for you all. I
am so thank full for the many hours spent not only throughout assessments but also through
the strength programs, participation in this study was a huge undertaking! You literally let me
into your homes, and into your lives. It was a true pleasure being able to work with you, and
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getting to know each of you. Particularly to my awesome little participants, you inspired me,
and were the biggest motivators anyone could ask for. I dedicate this thesis to you.
Mum and Dad, thank you so so so much for your unwavering support, encouragement and for
putting up with me, I know it can’t have been easy. I hope you both know how much I
appreciate your support and love. The way you both live your lives is an inspiration, you
brought me up ready to take on anything and everything, and I thank you for this. To my big
sisters Ceinwen and Bronwen (and my very big brother-in-law Andy) you have been the best
siblings I could ever ask for. Thank you for helping me survive these last few years, whether it
be by listening to my problems, feeding me, distracting me, or lending me clothes for
conferences. I love you all to bits.
To my friends, thank you for being there for me even when I have not been. You have provided
some lovely distractions and have been so understanding of my ventures. To my co-inhabitants
of 1.55 (and surrounding offices); thank you for the many hours of conversation, chocolate,
laughter and company. Nothing can match the advice and help you have given me, and the
distractions you have provided me, whilst at times you may not have helped me complete my
work, you definitely kept me sane.
Jack, thank you for putting up with me and my thesis (and laptop), allowing me to put you
second over all these years, comforting me through the (very frequent) times of distress and
celebrating with me over each small triumph. I know you put up with a lot, and you always
listened, or at least pretended to listen, to me agonising over each and every detail related to
this thesis. Thank you for being there for me.
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PUBLICATIONS AND ABSTRACTS
The following is a list of publications and abstracts to which I have contributed during the
course of my candidature, arising both directly and indirectly from this thesis. The published
manuscript and all abstracts are included in the Appendices section of this Thesis.
PEER REVIEWED PUBLICATIONS
1. Williams S, Reid S, Valentine J, Blair E, Smith N, Shillington T, Elliott C. The combination of
strength training and Botulinum Neurotoxin Type-A in children with Cerebral Palsy: The
effect on activity, participation & quality of life. Disabil Rehabil. 2012. In Review.
2. Williams S, Elliott C, Valentine J, Blair E, Reid S. Improving the gait of children with
Cerebral Palsy using the combined interventions of strength training and Botulinum
Neurotoxin Type-A. Gait Posture. 2012. In Review
3. Williams S, Reid S, Elliott C, Shipman P, Valentine J. Morphological alterations in spastic
muscles immediately following Botulinum Toxin Type-A treatment in children with
Cerebral Palsy. Dev Med Child Neurol. In Review
4. Williams S, Elliott C, Valentine J, Gubbay A, Shipman P, Reid S. Combining Strength
Training and Botulinum Neurotoxin intervention in children with Cerebral Palsy: The
impact on Muscle Morphology and Strength. Disabil Rehabil. 2012. Accepted for
publication
5. Pitcher C, Elliott C, Williams S, Licari M, Kuenzel A, Shipman P, Valentine J, Reid S.
Childhood muscle morphology and strength: alterations over six months of growth. Muscle
Nerve. 2012; In Press.
6. Calley A, Williams S, Reid S, Blair E, Valentine J, Girdler S, Elliott C. A comparison of activity,
participation and quality of life in children with and without spastic diplegia cerebral palsy.
Disabil Rehabil. 2012; 34(15) 1306-10. Epub 2011 Dec 26.
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ABSTRACTS
1. S Williams, C Elliott, J Valentine, A Gubbay, P Shipman, S Reid. Combining strength training
and Botulinum Neurotoxin intervention in children with CP: The impact on muscle
morphology and strength. Presented at the AACPDM 66th annual Meeting. 2012 Toronto,
ON, Canada.
2. S Williams, C Elliott, J Valentine, N Smith, T Shillington, M Spits, S Reid. Strength training
results in stronger but not necessarily bigger muscles for children with Cerebral Palsy.
Presented at the AusACPDM 6th Biannual conference. 2012 Brisbane, QLD, Australia.
3. S Williams, C Elliott, J Valentine, A Gubbay, M Spits, S Reid. The immediate effect of
Botulinum toxin type-A on muscle morphology and strength in children with Cerebral Palsy.
Accepted for presentation at the AusACPDM 6th Biannual conference. 2012 Brisbane, QLD,
Australia.
4. Williams S, Elliott C, Valentine J, Gubbay A, Spits M, Shipman S, Reid S. The immediate
effect of Botulinum Toxin Type-A on muscle morphology and strength in children with
Cerebral Palsy. Presented at the AACPDM 65th annual meeting. 2011 Las Vegas, Nevada,
USA. *Received Mac Keith Press Promising Career Award for best paper
5. C Elliott C, Valentine J, Williams S, Shipman P, Kuenzel A, Pitcher C, Reid, S. Does MRIderived muscle size relate to strength in children with and without Cerebral Palsy?
Presented at the AACPDM 64th annual Meeting. 2010 Washington, DC, USA.
6. Elliott C, Reid S, Williams S, Pitcher C, Kuenzel A, Shipman P, Valentine J. The relationship
between muscle morphology and strength in children with and without Cerebral Palsy.
Presented at the AusACPDM Conference, 2010, Christchurch, New Zealand.
7. Williams S, Reid S, Valentine J, Dwyer B, Kuenzel A, Shipman P, Elliott C. The effectiveness
of practice to prepare children for MRI Scans. Poster displayed at the ANZSPR conference,
2010, Margaret River, Western Australia.
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TABLE OF CONTENTS
ABSTRACT ..................................................................................................................................... iii
ACKNOWLEDGEMENTS ................................................................................................................ vi
PUBLICATIONS AND ABSTRACTS ............................................................................................... viii
TABLE OF CONTENTS ..................................................................................................................... x
LIST OF TABLES ........................................................................................................................... xiii
LIST OF FIGURES ......................................................................................................................... xiv
CHAPTER ONE ................................................................................................................................ 1
INTRODUCTION ............................................................................................................................. 1
1.1 Introduction......................................................................................................................... 1
1.2 Statement of the Problem ................................................................................................... 4
1.3 Thesis Outline ...................................................................................................................... 5
1.4 Definition of Key Terms ..................................................................................................... 10
1.5 Limitations and Delimitations ........................................................................................... 10
1.6 References ......................................................................................................................... 11
CHAPTER TWO ............................................................................................................................. 18
REVIEW OF THE LITERATURE....................................................................................................... 18
2.1 Cerebral Palsy .................................................................................................................... 18
2.2 The International Classification of Functioning, Disability and Health. ............................ 19
2.2.1 Body Function and Structure ...................................................................................... 20
2.2.2 Activity and Participation............................................................................................ 24
2.2.3 Contextual Factors ...................................................................................................... 26
2.3 Therapeutic Interventions ................................................................................................. 27
2.3.1 Botulinum Toxin Type-A ............................................................................................. 28
2.3.2 Functional Outcomes of Botulinum Toxin Type-A ...................................................... 29
2.3.3 Strength training ......................................................................................................... 31
2.3.4 Functional outcomes of Strength Training ................................................................. 33
2.4 The Next Step in Cerebral Palsy Therapy .......................................................................... 36
2.5 Summary ........................................................................................................................... 38
2.6 References ......................................................................................................................... 40
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CHAPTER THREE........................................................................................................................... 58
Morphological Alterations in Spastic Muscles Immediately Following Botulinum Neurotoxin
Type-A Treatment in Children with Cerebral Palsy. ..................................................................... 58
Foreword ................................................................................................................................. 59
3.1 Abstract ............................................................................................................................. 60
3.2 Introduction....................................................................................................................... 61
3.3 Methods ............................................................................................................................ 62
3.4 Results ............................................................................................................................... 65
3.5 Discussion .......................................................................................................................... 70
3.6 Clinical Implications ........................................................................................................... 72
3.7 Acknowledgements ........................................................................................................... 73
3.8 References ......................................................................................................................... 74
CHAPTER FOUR ............................................................................................................................ 77
Combining Strength Training and Botulinum Neurotoxin Type-A Intervention in Children with
Cerebral Palsy: The Impact on Muscle Morphology and Strength .............................................. 77
Foreword ................................................................................................................................. 78
4.1 Abstract ............................................................................................................................. 79
4.2 Introduction....................................................................................................................... 80
4.3 Methods ............................................................................................................................ 81
4.4 Results ............................................................................................................................... 86
4.5 Discussion .......................................................................................................................... 93
4.6 Clinical Implications ........................................................................................................... 97
4.7 Acknowledgements ........................................................................................................... 97
4.8 References ......................................................................................................................... 98
CHAPTER FIVE ............................................................................................................................ 101
Improving the Gait of Children with Cerebral Palsy using the Combined Interventions of
Strength Training and Botulinum Neurotoxin Type-A. .............................................................. 101
Foreword ............................................................................................................................... 102
5.1 Abstract ........................................................................................................................... 103
5.2 Introduction..................................................................................................................... 104
5.3 Methods .......................................................................................................................... 105
5.4 Results ............................................................................................................................. 108
5.5 Discussion ........................................................................................................................ 112
5.6 Conclusion ....................................................................................................................... 114
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5.7 Acknowledgements ......................................................................................................... 114
5.8 References ....................................................................................................................... 116
CHAPTER SIX .............................................................................................................................. 119
The Combination of Strength Training and Botulinum Neurotoxin Type-A in Children with
Cerebral Palsy: The Effect on Activity, Participation and Quality of Life ................................... 119
Foreword ............................................................................................................................... 120
6.1 Abstract ........................................................................................................................... 121
6.2 Introduction..................................................................................................................... 122
6.3 Methods .......................................................................................................................... 123
6.4 Results ............................................................................................................................. 127
6.5 Discussion ........................................................................................................................ 131
6.6 Conclusion ....................................................................................................................... 134
6.7 Acknowledgements ......................................................................................................... 135
6.8 References ....................................................................................................................... 136
CHAPTER SEVEN ........................................................................................................................ 140
Synthesis of results and Conclusion ........................................................................................... 140
7.1 Summary ......................................................................................................................... 140
7.2 Conclusions...................................................................................................................... 150
7.2.1 Future Research ........................................................................................................ 152
7.2.2 Significance of this Research .................................................................................... 153
7.3 References ....................................................................................................................... 155
APPENDICES ............................................................................................................................... 159
APPENDIX A- Published Manuscript ..................................................................................... 159
APPENDIX B- Accepted Abstracts ......................................................................................... 165
APPENDIX C- Supplementary Data for Chapter Three .......................................................... 179
APPENDIX D- Princess Margaret Hospital Ethical Approval.................................................. 184
APPENDIX E- The University of Western Australia Ethical Approval .................................... 186
APPENDIX F- Parent and Participant Information and Consent forms ................................. 187
APPENDIX G- Selective Control Assessment of the Lower Extremity (SCALE) ...................... 195
APPENDIX H- Canadian Occupational Performance Measure (COPM) ................................ 195
APPENDIX I- Assessment of Life Habits (LIFE-H) ................................................................... 199
APPENDIX J- Cerebral Palsy Quality of Life Questionnaire (CP-QOL) ................................... 206
APPENDIX K - Example of a 10 week Home Based Strength program.................................. 211
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LIST OF TABLES
CHAPTER TWO
Table 1 General youth resistance training guidelines as set by the National Strength and
Conditioning Association.............................................................................................................33
CHAPTER THREE
Table 1 Muscle volumes and strength of the lower leg for 15 children (30 legs) receiving BoNTA to the gastrocnemius muscle group.........................................................................................67
Table 2 PRE and POST group averages, with the grouped average of each individuals
percentage change in muscle volumes of the thigh for 10 children (20 legs) receiving BoNT-A to
the gastrocnemius muscle group and for 5 children (10 legs) receiving BoNT-A to the medial
hamstirngs and gastrocnemius...................................................................................................68
Table 3 PRE and POST average values of knee flexor and knee extensor strength (Isometric
peak torque), with the grouped average of individual percentage changes in 10 children (20
legs) receiving BoNT-A to the gastrocnemius muscle group, and 5 children (10 legs) receiving
BoNT-A to the medial hamstrings and gastrocnemius................................................................69
CHAPTER FOUR
Table 1 Mean change in strength and muscle volume scores for eight children over a 6 month
control period of BoNT-A, and over a 6 month intervention period of strength training and
BoNT-A........................................................................................................................................87
Table 2 Mean change in strength and muscle volume scores for both PRE and POST groups
over their respective 10 weeks of strength training, and 6month intervention of strength
training and BoNT-A....................................................................................................................90
CHAPTER FIVE
Table 1 Mean within-subject changes of the Gait Deviation Index (GDI), and the Hip, Knee and
Ankle joint power generation and absorption over 6 months of the PRE group (training before
BoNT-A), of the POST group (training after BoNT-A), and of the entire CP cohort...................110
CHAPTER SIX
Table 1 Mean within-subject change of scores for outcome measures of activity, participation
and QOL for the control and intervention period (n=8)............................................................128
Table 2 Mean within-subject changes for outcome measures of Activity, Participation and QOL,
with changes shown over the 10 weeks of strength training and 6 months............................130
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LIST OF FIGURES
CHAPTER TWO
FIGURE 1 The International Classification of Functioning, Disability and Health Framework.......20
CHAPTER THREE
FIGURE 1 Creating a 3 Dimensional model of the leg from an MRI scan using Mimics software
to determine muscle volume....................................................................................................64
CHAPTER FOUR
Figure 1 Cross-comparison study design, with a pre-intervention baseline assessment for eight
participants forming a control and intervention period.............................................................83
Figure 2 Mean scores for the Knee Flexor and Knee Extensor strength, and the Hamstring and
Quadriceps muscle volumes for the PRE and POST group over assessment time points. .........92
Figure 3 Mean scores for Gastrocnemius and Tibialis Anterior strength, and the Plantar Flexor
and Dorsi Flexor muscle volumes for the PRE and POST group over assessment time
points...........................................................................................................................................93
CHAPTER FIVE
Figure 1 Cross-comparison study design, with a pre-intervention baseline assessment (B) for 8
participants forming a control period, and 15 children completing the intervention
period........................................................................................................................................106
Figure 2 Average power generation (peak), and power absorption (area) at the hip, knee and
ankle joints through stance, before and after a control period (of BoNT-A with normal clinical
care) for eight children..............................................................................................................109
Figure 3 Average power generation (peak), and average power absorption (area) at the Hip,
Knee and Ankle joints through the stance phase of gait for the children in the PRE and POST
group, and of all the children in the study grouped together...................................................112
CHAPTER SIX
participants forming a control period, and 15 children completing the intervention
period........................................................................................................................................124
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CHAPTER ONE
INTRODUCTION
1.1 INTRODUCTION
Cerebral Palsy (CP) is one of the most common and widely recognised childhood physical
disabilities in the world1 with an estimated prevalence of 2.0 to 2.5 for every 1000 live births2.
CP was most recently defined as;
‘a group of permanent disorders of the development of movement and
posture causing activity limitation that are attributed to non-progressive
disturbances that occurred in the developing foetal or infant brain. The motor
disorders of cerebral palsy are often accompanied by disturbances of
sensation, perception, cognition, communication, and behaviour, by epilepsy
and by secondary musculoskeletal problems.’ 3, 4
This definition highlights the disorder of movement and posture as a neurological disorder
with evolving clinical manifestations and musculoskeletal problems as the child matures. With
the damage to the developing brain permanent with (presently) no known cure, the aim of
current treatment modalities is to manage outward expressions of the disorder5. Health
professionals currently utilise the World Health Organisation’s International Classification of
Functioning, Disability and Health (ICF) as best practice for a holistic approach to the care,
management and rehabilitation of people with disabilities6. The ICF conceptualises an
individual’s health as a complex relationship between health-status, the impact this has on
body functions, body structures and activity, and how environmental and personal factors can
influence the level of participation in everyday settings. In determining the impact of a
treatment intervention, the use of the ICF framework guides clinicians in obtaining information
on all three dimensions of disablement and functioning (impairment, activity limitations and
participation restrictions). This provides a complete and holistic understanding, which in turn
may guide future therapeutic interventions. Interventions in CP are commonly targeted
towards managing the associated impairments, in an effort to address inefficient movement
and limitations in activities of daily living7. Spasticity and muscle weakness are common motor
problems associated with CP that are of functional importance, and therefore important to
address in clinical management. To date, published research is providing increasing evidence
of the value of treating spasticity and muscle weakness in CP, however further research needs
to examine the effects of treatments and treatment combinations at all levels of the ICF.
1
Of children with CP, 70% to 80% are classified as having spastic CP8. Spasticity is defined as a
velocity-dependant increase in the physiologic resistance of muscle to passive motion9, 10. In
CP, spasticity contains neurophysiological components including abnormalities in muscle tone,
primitive reflexes and movement and/or postural control response11. Spasticity in CP is also
considered to result in musculoskeletal changes including; abnormal changes in connective
tissue, muscles and bones and influence the rate of bone growth relative to muscle growth11.
Botulinum Neurotoxin type-A (BoNT-A) is widely used for the management of spasticity in
children with CP12, 13. Along with an acceptable safety profile14-18, the literature describes many
positive outcomes from BoNT-A treatment including; a reduction in muscle tone19-21, increase
in joint range of motion19-22, improved gait patterns19, 22, functional improvements23-27 and
delayed and reduced requirement for surgical interventions to treat musculoskeletal
deformities (when combined with conservative treatments)28, 29. However, generalised muscle
weakness16, 17, 30 and weakness in neighbouring non-targeted muscles31, 32 have been reported
as undesirable effects of BoNT-A treatment. In addition to this, there have been recent
publications raising concern, and calling for more research regarding the effect of BoNT-A on
muscle size and morphology, with indications of post BoNT-A atrophy in healthy adults’
muscles33, 34 and in animal studies35, 36. Considering the repetitive nature of BoNT-A treatment
for spasticity management in children with CP, it is necessary to understand the impact of this
treatment in this population, with regard to all aspects of the ICF.
It is well recognised that muscle structure and size are associated with muscle strength in the
adult and adolescent population37, 38. Children with CP have been shown to have smaller39,40
and weaker muscles41 than their typically developing peers. Over the last decade, weakness
has been increasingly recognised as a significant motor impairment42-45 purportedly affecting
the functional ability in children with CP25,
26
. Strength training is now recognised as an
effective intervention for improving muscular strength in children with CP46. A growing number
of studies confirm that following strength training, people with CP can achieve significant
strength improvements that translate to gains in motor function42, 46, 47 such as improvements
in walking42, 46, 47, flexibility, posture and balance48. McNee and Colleagues (2009)49 have also
reported that alongside improvements in strength, muscles also increase in volume after 5 and
10 weeks of strength training in children with CP. Whilst strength training can be implemented
to target muscular weakness (and also increase muscle size49), BoNT-A injections are in
common use for spasticity management12 (yet may serve to reduce muscle size33,
34,35,36
).
Spasticity and muscular weakness are two major motor impairments known to negatively
impact walking ability in CP50, interventions targeting both these impairments, and their effect
on walking gait have only recently received attention in the literature.
2
For people with mild diplegic CP, therapeutic goals are often directed towards improving the
ability to walk51. Strength training has demonstrated kinematic changes within gait, with
reports of; a more upright posture52, decrease in crouch52-55, improved hip and knee extension
through stance56, improved knee extension in late swing54, and trends of improved ankle dorsiflexion at swing and initial contact55. Similarly, BoNT-A treatment is also shown to have a
positive impact on gait, with reports of increases in ankle dorsiflexion20, 22, 57, knee extension at
initial contact57, and a normalisation of ankle kinetics57, 58 during gait. Impairment of walking
ability is significantly associated with reduced participation59. The ability and capacity to walk
makes daily life activities and social participation easier for all individuals with CP, and may be
especially important for children throughout their years of physical growth and development.
It is of concern that research demonstrates that children with CP experience greater activity
limitations and to be less physically active than their typically developing peers59-61. In addition
to this, compared with typically developing peers, children with CP report difficulties
participating in activities across home, school and in the wider community as a result of
restrictions in physical functioning and mobility62. Well-being, a ‘broad notion’ used by
researchers which considers quality of life63 (QoL), is also generally reported to be lower
amongst children with CP63. Information on the effect of BoNT-A and strength training (applied
separately or combined) on activity, participation and QoL domains of the ICF is sparse.
Whilst the two treatment interventions, of BoNT-A injections and strength training, may
already be administered in combination in some clinical settings, very little research has
formally applied and reported this combination of therapies within CP, and none have done so
and measured outcomes at all levels of the ICF. The concept of applying other forms of therapy
management in conjunction with BoNT-A is not new, however it seems that the focus of
combined interventions has been to potentiate the effect of the BoNT-A for spasticity
reduction64,65 such as stretching, range of motion exercise, serial casting, splinting/orthotics
and motor training66. Previous research has called for the need for therapeutic interventions to
address more than one impairment of CP if improvements in levels of activity and participation
are sought44, and is a logical direction for maximising functional outcomes. A recent pilot study
by Bandholm and colleagues(2012)67 included progressive resistance training to their physical
rehabilitation program following BoNT-A treatment of the ankle plantar flexors, which resulted
in increases in the maximal torque-generating capabilities of the plantar flexors, with a
simultaneous reduction in plantar flexor spasticity, and a trend of increased function67. This is
the first report formally assessing the combination of BoNT-A and strength training in the
3
lower limb, and highlights the need for a multidimensional approach to assessing the
combination of therapies using the ICF.
Furthermore, a question remains as to the most effective timing of the strength training in
relation to BoNT-A injections. It is unknown if strength training, applied prior to BoNT-A
injections will result in superior, equal or inferior outcomes compared to training undertaken
following BoNT-A treatment. This is pertinent in a clinical population, where funding
structures, family life, and other treatment plans inhibit year-round strength interventions. In
addition to this, the possibility of having an option of strength training before or after BoNT-A
may expand this as a treatment choice for families.
Home based programmes are
interventions specifically designed for implementation in the home and in the context of daily
life by families68. Home based strength training can be an effective and feasible method of
implementing strength training with children69, with potential cost savings and evidence of
increased adherence70. For the parents and families, the major advantage of home programs is
that they are more time efficient, requiring no travel to gym settings or institutions on their
part69. In previous literature, home programs with favourable outcomes tend to involve goal
setting, and individualisation of the program42, 68, 70. Further evidence supporting the use of
home based strength training, involving goal setting and individualisation of the program will
serve to promote this treatment method. Finally, this information will contribute new
knowledge and guidance for clinicians worldwide to enhance the overall outcome of current
BoNT-A therapy.
1.2 STATEMENT OF THE PROBLEM
CP is a physical disability that can significantly impact on an individual’s life and may
encompass all components of functioning. Spasticity and muscular weakness are two major
motor impairments associated with CP. BoNT-A is a commonly used treatment for spasticity
management, however research has linked BoNT-A with muscle weakness and muscle atrophy.
For a population already predisposed to weakness and decrements in muscle size, a frequently
used treatment that potentially leads to further weakening and atrophy of the muscle should
be well understood. In spite of this, the effect of BoNT-A on muscle strength and size in the CP
population has not been researched to date.
There is strong supportive evidence for the use of strength training to target muscular
weakness, and indications of increased muscle size in children with CP. With this in mind, it
seems logical to combine both BoNT-A treatment (for spasticity management) and strength
4
training (for muscular weakness) to target both impairments simultaneously. The only
published study67 of the combined effect of BoNT-A and strength training in the lower limb
reported only kinematic and functional outcomes, the combined effect of BoNT-A and strength
training on all other levels of the ICF remains undetermined. Could the combination of
therapies address issues other than muscle strength and spasticity at the impairment level?
Could this ameliorate the muscle size deficit in CP, avert the potential of post BoNT-A atrophy,
and improve outcomes of walking gait? Can an intervention, targeting the impairment level of
the ICF, also have ensuing improvements in other domains of activity, participation or quality
of life? Finally, can this intervention influence the achievement of functional goals? In
answering these questions, it is important to offer guidelines for implementing this
intervention, to determine if there is a more effective timing of strength training in relation to
BoNT-A, either administrated before or after the injection. This information is needed to guide
clinical decision making for children with CP and has the potential to improve clinical outcomes
for patients.
1.2.1 STUDY AIMS
The overarching aim of this study was to assess the combined effect of a home based, goal
directed, and individualised 10 week strength training program with BoNT-A injections for
spasticity management for children with CP. Specifically, this combined intervention will be
assessed at all levels of the ICF; investigating muscle strength, spasticity, muscle morphology,
walking gait, activity, participation, quality of life, and the attainment of functional goals. The
outcomes of the combined strength and BoNT-A therapies will be compared, where possible,
to changes measured over a control period of BoNT-A injections without the addition of a 10
week strength program (normal care routine).
A secondary aim is to determine the best practice in terms of timing of application of a
strength training intervention in relation to reception of BoNT-A for children with CP.
Specifically if outcomes are most improved if training is undertaken in the weeks preceding the
BoNT-A injection, or in the weeks after the injection.
1.2.3 SIGNIFICANCE OF THE STUDY
By targeting, what are commonly considered two of the most significant motor impairments of
CP, this is the first study to demonstrate the significant implications for the prescription of the
two combined therapies, and will do so with a multidimensional assessment at all levels of the
ICF. This will allow clinicians to make informed decisions when prescribing strength training
programs to children with CP who are also undergoing BoNT-A treatment for spasticity
5
management. Feedback regarding muscle morphological alterations following BoNT-A, in
particular, will provide the first look into CP muscle within the literature, and provide
important information, and recommendations for clinicians and future research. It is
anticipated that the results of this research will be disseminated widely to all medical and
therapy staff responsible for treatment and management of CP.
1.3 THESIS OUTLINE
The introduction establishes subject matter for this study, and in doing so, communicates the
research problem and approaches taken to answer the question. This thesis is presented as a
series of individual papers addressing one minor study and one major multidimensional study.
The minor study, the first paper, presents the effect of a single injection of BoNT-A on muscle
morphology, muscular strength, and function, and provides novel information to clinicians to
improve our understanding of the effects of this common treatment for spasticity
management in CP. This study also provides background information for the key focus of this
thesis. The major study relates to the outcomes of a 10-week home based strength training
programme combined with BoNT-A treatment for children with CP. This is presented as three
papers addressing the impacts on the major areas of investigation; (i) muscle strength,
spasticity, and muscle morphology, (ii) outcomes of walking gait, attainment of functional
goals, and (iii) activity, participation and quality of life. At times the presentation of
independent papers may seem repetitive; however it is felt that each paper should stand alone
for ease of reading, therefore references are provided at the conclusion to each individual
paper. The thesis is concluded with a synthesis of results and discussion. This thesis therefore
contains four separate but inter-related papers.
1.3.1 CHAPTER TWO- LITERATURE REVIEW
The literature review builds the context of the study through a comprehensive overview of
previously published research. Opening with a brief introduction to CP, the literature review
focuses on functional outcomes of CP, with particular attention to the motor impairments,
spasticity and muscular weakness. A review of treatment interventions follows, and focuses on
the use of BoNT-A for spasticity management, and strength training for muscle weakness.
Available literature pertaining to the effect of both of these interventions is reviewed at all
levels of the ICF. This will provide the reader with a greater understanding of the literature
presently available to us, and to the ‘gaps’, where further research is needed.
6
1.3.2 CHAPTER THREE- PAPER ONE
MORPHOLOGICAL ALTERATIONS IN SPASTIC MUSCLES IMMEDIATELY FOLLOWING
BOTULINUM NEUROTOXIN TYPE-A TREATMENT IN CHILDREN WITH CEREBRAL PALSY.
The aims of this paper are to:

To provide the first known documentation of the morphologic alterations of
spastic muscles in response to BoNT-A.

To report morphologic response in synergist and antagonist muscle to BoNT-A
treatment in spastic muscle

To increase understanding of the effect of BoNT-A treatment on muscle
strength and functional ability in children with CP.
It was hypothesised that

Muscles injected with BoNT-A would display a reduction in muscle volume.

BoNT-A induced muscle atrophy would also result in a reduced force generating
capacity.
1.3.3 CHAPTER FOUR- PAPER TWO
COMBINING STRENGTH TRAINING AND BOTULINUM NEUROTOXIN TYPE-A
INTERVENTION IN CHILDREN WITH CEREBRAL PALSY: THE IMPACT ON MUSCLE
MORPHOLOGY AND STRENGTH.

To combine a 10 week, home based, strength training programme with BoNT-A
injections and measure the effects on muscular weakness and spasticity in CP.

To determine if the combined interventions would be more successful in improving
muscle strength and reducing spasticity than BoNT-A and the current normal care.

To determine if changes in muscle strength could be attributed to alterations in muscle
morphology.

To report if the combination of therapies would successfully improve individual
functional goals set by the children in this study compared with BoNT-A and the
current normal care.

To determine if the timing of strength training, whether it be administered before or
after BoNT-A injections, affects outcomes, thereby indicating whether there is an
optimal timing of strength training.
7

Provide guidelines for further rehabilitation planning to enhance therapy outcomes for
children with CP.
It is hypothesised that:

The combination for strength training and BoNT-A will result in the simultaneous
increase of muscle strength and reductions in muscle spasticity.

The 10 week strength intervention will evoke increases in the muscle size of targeted
muscles.

The combined intervention program, including individual goal-directed strength
exercises, will result in functional goal-attainment, as measured by the Goal
Attainment Scale (GAS).

Children undertaking strength training in the weeks after BoNT-A treatment will have
better outcomes of muscle strength, morphology and functional goals than those
receiving strength training before BoNT-A treatment.
1.3.4 CHAPTER FIVE- PAPER THREE:
IMPROVING THE GAIT OF CHILDREN WITH CEREBRAL PALSY USING THE COMBINED
INTERVENTIONS OF STRENGTH TRAINING AND BOTULINUM NEUROTOXIN TYPE-A.

To measure the effects of combining a 10 week, home based, strength training
programme with BoNT-A injections (to target both muscular weakness and spasticity)
in CP on walking gait evaluated with the Gait Deviation Index (GDI) and kinetic power
profiles.

To determine if the timing of strength training, whether it be administered before or
after BoNT-A injections, affects outcomes, thereby indicating whether there is an
optimal timing of strength training.

Provide guidelines for further rehabilitation planning to enhance therapy outcomes for
children with CP.

The combination for strength training and BoNT-A will improve measures of the GDI,
indicating children in the study to be walking closer to the style of non-pathological
walking gait.
8

The 10 week strength intervention will improve kinetic power profiles at the hip, knee
and ankle joints so that they more closely resemble those of typically developing
peers.

Children undertaking strength training after BoNT-A treatment will have better GDI
outcomes (or will have a more normal gait) than children undertaking strength training
in the weeks preceding BoNT-A treatment.
1.3.5 CHAPTER SIX- PAPER FOUR
THE COMBINATION OF STRENGTH TRAINING AND BOTULINUM NEUROTOXIN TYPEA IN CHILDREN WITH CEREBRAL PALSY: THE EFFECT ON ACTIVITY, PARTICIPATION
AND QUALITY OF LIFE.

To determine if a combined 10 week, home based, strength training programme with
BoNT-A injections (targeting both muscular weakness and spasticity) in CP at the
impairment level of the ICF can evoke changes at the activity, participation or quality
of life domains of the ICF, compared with BoNT-A injections and normal care.

To determine if the timing of the strength training program, administered around
scheduled BoNT-A injections will produce different outcomes on the activity,
participation and QoL domains of the ICF.

The combined interventions will improve measures of activity, as assessed by
the Timed Up and Go (TUG) and the Six-Minute Walk Test (6MWT)

Children with CP will have improved outcomes of participation following their
involvement in the study (as assessed by the Assessment of Life-Habits, the
LIFE-H, for children).

Children with CP will have improved outcomes of QoL following their
involvement in the study (as assessed by the Cerebral Palsy Quality of Life
Questionnaire for Children, CP QOL).
1.3.6 CHAPTER SEVEN
SYNTHESIS OF RESULTS AND CONCLUSIONS
9
The final chapter aims to provide an overall synthesis of results presented throughout the
thesis, integrating the major findings from each study and provides an overall conclusion of the
research programme in its entirety.
1.4 DEFINITION OF KEY TERMS
C EREBRAL P ALSY : “Cerebral palsy (CP) describes a group of disorders of the development of
movement and posture, causing activity limitation, that are attributed to non-progressive
disturbances that occurred in the developing fetal or infant brain. The motor disorders of
cerebral palsy are often accompanied by disturbances of sensation, cognition, communication,
perception, and/or behaviour, and/or by a seizure disorder.” pg 572 71
S PASTICITY : A velocity-dependent increase in muscle resistance, in response to a passive
stretch9.
M USCLE W EAKNESS : a failure or inability to produce or maintain an anticipated level of force72.
S TRENGTH TRAINING : A method of improving muscular strength by gradually increasing the
ability to resist force through the use of free weights, machines, or the person's own body
weight73.
F UNCTION : A complex entity that incorporates physical capability and performance, as well as
psychological, social and cognitive capability6.
B ODY FUNCTIONS AND STRUCTURES : The physiological functioning of the anatomical structures
of the organs, limbs and their components6
I MPAIRMENT : Problems with body functions and structures, such as a deviation or loss6.
A CTIVITY : The execution of a task or activity by an individual6.
P ARTICIPATION : Ones involvement in life situations6.
Q UALITY OF L IFE : An individual’s perception of their position in life in the context of the culture
and value systems in which they live, and in relation to their goals, expectations, standards,
and concerns74.
1.5 LIMITATIONS AND DELIMITATIONS
1.5.1 LIMITATIONS
Limitations regarding the individual experience of CP and BoNT-A can lead to difficulties when
comparing data, however reflects the clinical reality of this study. CP is a disorder that
manifests itself differently in each child, therefore in following with best practice care, each
child received individualised variations of the program. The strength training program is based
on the child’s individual goals developed with the assistance of an Occupational Therapist and
the parent using the Canadian Occupational Performance Measure75. The muscles targeted for
10
inclusion in the training therefore varied between participants, with some children unable to
include training of the gastrocnemius muscle due to varying levels of contracture. For example,
a child aiming to be able to ‘run faster’ would have the muscle groups that are important for
running included in their program, e.g. generally the hip flexors, gluteal, quadriceps,
hamstrings and calf muscles (where appropriate). The muscle(s) selected for injection and the
total dose of BoNT-A (Botox®, Allergan, Irvine, CA, USA), were determined by the child’s
physician based on clinical assessment and functional goal setting,
Imposed by limited time and limited number of locally available appropriate participants, a
primary limitation of this study is a lack of a control period for each participant (of BoNT-A
only). The next best possible option was to allocate children into a control period, and follow
with an intervention period, whereby participants were randomly allocated to either PRE or
POST BoNT-A training. A random selection of our participants were able to complete the
control period, yet we are still limited to the fact that not all of the participants in our study
underwent a control period. In addition to this, the lack of a randomised control group, against
which the interventions could be directly compared, means that factors such as growth,
maturation and time are not well controlled for and therefore is a limitation of this study.
Activities undertaken that were not related to the program (i.e. swimming lessons, after school
sport etc) were monitored throughout the course of the research period to ensure that they
were maintained as a constant throughout control and intervention periods however this
could not be controlled.
1.5.2 DELIMITATIONS
This study is delimited by the inclusion of children aged 5-12 years as a clinically appropriate
age range for children receiving BoNT-A for spasticity management before the need for
orthopaedic surgery. Inclusion criteria also include a classification of Spastic Diplegic CP and
only children classified as having a Gross Motor Function Classification System76 (GMFCS) level
of I-II. In an attempt to minimise the confounding negative effect of immobility on strength,
children with a GMFCS classification level of III, IV and V (denoting children with limited selfmobility) were excluded from this study. Precise timing of strength training related to BoNT-A
injection meant that each strength training program occurred at the appropriate time in
relation to the effect of BoNT-A. This study is also delimited due to the assessment protocols,
many of which can only be conducted in a laboratory setting, including; isokinetic and
isometric strength assessments, three-dimensional motion analysis, and magnetic resonance
imaging for assessment of muscle morphology following set protocols.
11
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Calley A, Williams S, Reid S, et al. A Comparison of Activity, Participation and Quality of
Life in Children with and without Spastic Diplegia Cerebral Palsy. Disabil Rehabil. 2012;34:130610.
64.
Livingston M, Rosenbaum P, Russell D, Palisano R. Quality of life among adolescents
with cerebral palsy: what does the literature tell us? Dev Med Child Neurol. 2007;49:225-31.
65.
Boyd R, Graham H. Botulinum toxin A in the management of children with cerebral
palsy: indications and outcome. Eur J Neurol. 1997;4:15-22.
66.
Graham H, Aoki K, Autti-Ramo I, et al. Recommendations for the use of botulinum
toxin type A in the management of cerebral palsy. Gait Posture. 2000;11:67-79.
67.
Goldstein E. Spasticity management: an overview. J Child Neurol. 2001;16:16-23.
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68.
Bandholm T, Jensen B, Nielsen L, et al. Neurorehabilitation with versus without
resistance training after botulinum toxin treatment in children with cerebral palsy: A
randomized pilot study. NeuroRehabilitation. 2012;30:277-86.
69.
Novak I, Cuisick A. Home programmes in paediatric occupational therapy for children
with cerebral palsy: Where to start? Aust Occup Ther J. 2006;53:251-64.
70.
Dodd K, Taylor N, Graham H. A randomized clinical trial of strength training in young
people with cerebral palsy. Dev Med Child Neurol. 2003;45:652–7.
71.
Novak I. Effective home programme intervention for adults: a systematic review. Clin
Rehabil. 2011 August 10, 2011.
72.
Bax M, Goldstein M, Rosenbaum P, Leviton A, Paneth N. Proposed definition and
classification of cerebral palsy, April 2005. Dev Med Child Neurol. 2005;47:571-6.
73.
Edwards R. Physiological analysis of skeletal muscle weakness and fatigue. Clin Sci Mol
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74.
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Palisano R, Rosenbaum P, Walter S, et al. Development and Reliability of a System to
Classify Gross Motor Function in Children with Cerebral Palsy Developmental Medicine and
Child Neurology. 1997;39:214.
77.
Law M, Baptise S, Carswell A, McColl M, Polatajko H, Pollock N. Canadian Occupational
Performance Measure. Third ed. Ottawa: CAOT Publications ACE; 1998.
17
CHAPTER TWO
REVIEW OF THE LITERATURE
This literature review will open with a brief introduction to Cerebral Palsy (CP), with a focus on
spastic diplegia, the target population of this thesis. The review then introduces The
International Classification of Functioning Disability and Health (ICF) and explores the impact
of CP at the level of body functions and structures, activity and participation and the impact on
an individual’s quality of life. There are numerous impairments to body function and structures
associated with CP. Spasticity and muscle weakness are the focus of this research, and special
attention is given in this review to the impact of both motor impairments. Followed by
discussion of Botulinum Neurotoxin Type-A (BoNT-A) and strength training as treatment
options to counteract spasticity and muscle weakness. This discussion will encompass research
pertaining to outcomes across the levels of body structures and function, activity, participation
and quality of life of children with CP. The final objective of this review is to investigate the
combination of strength training and BoNT-A therapy in children with CP.
2.1 CEREBRAL PALSY
Cerebral Palsy (CP) is one of the most common and widely recognised childhood physical
disabilities in the world with an estimated prevalence of 2.0 to 2.5 for every 1000 live births1.
The term ‘Cerebral Palsy’ describes a group of disorders of the development of movement and
posture due to non-progressive disturbances in the immature brain2. Although the lesion is
static, the disorder of movement or posture is usually not unchanging and has a wide variety of
musculoskeletal problems and other associated conditions that manifest as the child matures
and develops. Some of the frequent motor impairments resultant from the neural deficits
include spasticity, dystonia, muscle contractures, in-coordination, loss of selective motor
control, and muscle weakness3.
Spasticity is the most common motor impairment in children with CP, with 70% to 80% of CP
children classified as spastic4. Up to 50% of children with spastic CP have diplegia, the most
common subtype of CP5, 6. Diplegia is characterised by a greater involvement in the lower
extremities than the upper extremities2. Children with spastic diplegic CP generally require
various interventions to be able to walk independently, with many using walking aids and
eventually requiring surgery for contractures and deformities6, 7. The Gross Motor Function
18
Classification System8 (GMFCS) was developed to provide an objective classification of the
patterns of motor disability in children with CP. Functional mobility is divided into five levels:
children in Level I have the most independent motor function and children in Level V have the
least, with clinically meaningful distinctions between the levels based on functional abilities
and limitations8. The most common classifications for children with CP are GMFCS I (32-52%)
and GMFCS II (17-21%) these children can be described as having the ability to walk
independently, without the need for assistive mobility aids8. Children who are classified as
spastic diplegic, GMFCS I and II therefore comprise a large portion of those with CP, though are
considered as being on the higher end of the functional scale. With the motor impairments of
CP affecting many aspects of an individual’s life, the aim of many current treatment modalities
is to manage outward expressions of the disorder9. Therefore a multidimensional approach to
treatment and the evaluation of treatment interventions is of high relevance.
2.2 THE INTERNATIONAL CLASSIFICATION OF FUNCTIONING, DISABILITY AND HEALTH.
The World Health Organisation (WHO) recognises that functioning is more than just one’s
ability to move10. Functioning is defined as a complex entity that incorporates physical
capability and performance, as well as psychological, social and cognitive capability10. The
International Classification of Functioning Disability and Health (ICF)11 is a theoretical
classification scheme devised by the WHO, that incorporates all of these aspects of
functioning. It offers a scientific tool for understanding human function and disability for
clinical, research and other public health purposes11.
“Functioning” and “disability” are umbrella terms that are conceived as a dynamic interaction
between health conditions (e.g., disorders, diseases,
injuries) and contextual factors
(environmental, personal factors)12. The ICF provides a generalised framework for
understanding the dimensions of disability and functioning with respect to the body, the whole
person, and the whole person in a social context. The ICF is composed of two parts; (i)
functioning and disability; which comprise body functions, body structures, activity and
participation and (ii) contextual factors which are made up of environmental factors and
personal factors (Figure 1)10. Whilst domains of the ICF are separately defined, each is interrelated to encompass overall function of a health condition.
19
Figure 1 The International Classification of Functioning, Disability and Health (ICF)
Framework10
The ICF is a framework that captures the breadth of difficulties experienced by those with CP
and the many areas of impact13. It promotes a broad application of outcome measures that
ensures interventions and rehabilitation programs are being evaluated, not only at the level of
the organ system (impairments), but also at the individual (activity limitations) and societal
levels (participation restrictions)14. For example, whilst an intervention may result in
improvement at the level of body function and activity, this does not necessarily mean there
will be improvements in participation or family satisfaction15. The philosophy behind the ICF
has resulted in a shift of therapeutic focus from impairment prevention to maximising overall
health status16. The ICF has been shown to be valuable in assessing the efficacy of
rehabilitation services in the CP population17, 18, and will be utilised in this literature review to
describe functional limitations for children with CP and the impact of interventions at each
level of the ICF.
2.2.1 BODY FUNCTION AND STRUCTURE
The first component of the ICF ‘functioning and disability’ includes body functions and
structures which refer to the physiological functioning of the anatomical structures of the
organs, limbs and their components. Problems, such as deviation or loss, are referred to as
impairments10.
Spasticity, weakness, dystonia, muscle contractures, bony deformities, in-coordination and loss
of selective motor control are amongst the list of possible motor impairments associated with
CP; with sensory deficits also adversely impact a child’s functioning3. However, for the scope of
20
this literature review, spasticity and muscle weakness will be the focus for investigation, as
two common impairments of CP that may co-exist in the same muscle19, 20.
2.2.1.1 SPASTICITY
Spasticity is defined as a velocity-dependant increase in the physiologic resistance of muscle to
passive motion21, 22. The motor impairment is often associated with overactive stretch reflexes,
loss of dexterity, and weakness23. It is thought that by inhibiting the muscles ability to stretch,
spasticity can also inhibit growth in the length of the muscle, resulting in a decreasing range of
joint motion24 and culminating in the development of muscle contracture25. As a consequence
of spasticity, individuals often report muscle stiffness, pain or discomfort, loss of function in
the extremities, and difficulties in maintain standing and/or sitting posture26. The effect of
spasticity on locomotive and gross motor patterns is evident, although variable in children with
CP27, 28.
Ambulant children with spastic diplegic CP are reported to adopt a range of gait patterns
observable in the sagittal plane24, 29. Described by Sutherland and Davids (1993)30, and further
classified by Rodda and Colleagues (2004)29 typical gait patterns of CP include crouch gait, jump
knee, stiff knee, and recurvatum knee; with equinus or equinovalgus foot and an internally
rotated hip also commonly reported24,
29-31
. Collectively referred to as `lever arm disease',
torsional deformities of the long bones and foot deformities frequently contribute to gait
alterations observable in the transverse plane31. The differing characteristics of gait may be
explained by the presence of spasticity within different muscles groups; the flexors of the hip
and the knee and plantar flexors of the ankle are the key muscle groups, displaying spasticity
and contracture, affecting the pattern of gait29. Crouch gait, for example, may a result of overactivity or shortening of the hamstrings32, and can be identified by excessive flexion at the hip
and knee, and excessive dorsi flexion at the ankle, whilst equinus walking is related to plantarflexor spasticity33. However, it is important to note that whilst spasticity is a significant
impacting factor of these gait patterns, other factors are also influential; co-contractions may
interact with torsional deformities of the femur and tibia, in addition to poor selective motor
control and muscular weakness29.
2.2.1.2 MUSCLE WEAKNESS
As indicated by the nomenclature ‘cerebral palsy’, meaning weakness originating at the brain,
muscular weakness has long been recognised as a primary clinical feature of CP34. The term
21
‘weakness’ implies a failure or inability to produce or maintain an anticipated level of force 35.
Over the last decade, weakness has been increasingly recognised as a significant motor
impairment36-39, purportedly affecting the functional ability in children with CP40, 41. Muscular
weakness is a pervasive symptom in CP; Wiley and Damiano (1998)38 demonstrated that
children with diplegic CP were weaker than typically developing children in all major muscle
groups of the lower extremities, even the highly functional ambulatory children with spastic
diplegic CP38. Literature demonstrates muscle weakness to be most pronounced in the plantar
flexors, knee flexors and hip abductors and extensors37, 38, 42-44 in children and adolescents with
CP. Additionally, a number of reports have also identified concentric and eccentric weaknesses
in individuals with CP38, 45-47.
The past assumption that deficient performance of the agonist muscle was due to antagonist
spastic restraint, has been superseded by the contention that the major cause of muscle
weakness is now primarily due to agonist deficiency48. In fact the literature suggests that the
extent of muscular weakness is independent of the presence of spasticity38, 39, 49, 50. Ross and
Engsberg (2002)39 suggest that spasticity is not related to strength in individuals with CP,
revealing that whilst spasticity was not always present in muscles with CP, muscular weakness
almost always was39.
The weakness found in children with CP can be attributable to both altered neural mechanisms
and muscle tissue changes36. Many believe low force production is due to either inability to
maximally activate muscle or a decrease in motor unit discharge rate38,
47, 51, 52
. Decreased
central drive, incomplete motor unit recruitment, and increased agonist/antagonist coactivation are all neurological factors of muscular weakness suggested to exacerbate the
inability of the child with CP to produce high levels of muscle force, work and power,
consequently affecting motor performance34, 38, 46, 48, 52. It is likely that these factors are not
mutually exclusive, but integrally related to contribute to muscle weakness.
Changes in the mechanical properties of the muscles observed in CP may, in part, account for
decreased muscle force production53. There is increasing evidence to confirm that spastic
muscles show differences in structural morphology that may affect force generation
capabilities53-55. Muscle structure and size is associated with muscle strength in the adult and
adolescent population55, 56, and Pitcher and Colleagues (2012)57 reported strong associations
between muscle size and strength in typically developing children57. This factor is particularly
22
relevant when we consider that children with CP are shown to have smaller muscles then their
typically developing peers57. A recent review of the literature in spastic CP found consistent
evidence for small muscle size as indicated by reduced muscle volume, cross sectional area,
thickness and belly length in comparisons of paretic muscles with non-paretic and typically
developing muscles58. Barber and Colleagues (2009)59 have described volumetric deficits in the
medial gastrocnemii of young children (2–5y) with spastic CP of 22% compared with typically
developing children59. Elder and Colleagues (2003) 52 demonstrated the calf musculature of the
paretic limbs of children with spastic hemiplegic CP to be on average 73% of the volume of the
non-paretic limb52. Similarly Malaiya and Colleagues (2007)
60
reported the medial
gastrocnemius in the paretic limb to be approximately two-thirds of the volume of the muscle
in the non-paretic or in typically developing limbs60. Whilst in a group of young adults with
spastic hemiplegic CP, Lampe and Colleagues (2006)61 reported all the muscles in the affected
lower limb to be smaller than those in the unaffected limb61. It is clear that both neural and
structural mechanisms may impair the muscle of children with CP to work to its true functional
capacity.
Functional limitations of both the upper and lower extremities are a consequence of a plethora
of neural and muscular impairments present in the CP population; muscular impairments
include abnormal muscle tone, muscular weakness, a variety of muscle synergies, muscular
tendon contracture,
patterns of co-activation, decreased inhibition of reflexes, altered
biomechanics and inadequate muscle force production46, 51, 62, 63. Whilst many of the muscular
impairments are related to movement deficits44, 49, 64, lower extremity muscle weakness has
shown a stronger association with walking parameters than other motor impairments in CP 39,
65, 72
. Using the Gross Motor Function Measure (GMFM)66, Ross & Engsberg (2007) reported
muscle strength to correlate significantly with 11 of the 15 variables tested42. In particular,
across the GMFM dimension of walking, running and jumping, where gait speed, stride length,
knee flexion at initial contact, pelvic tilt and range of motion during gait were all associated
with increased weakness42. Muscular strength is positively associated with walking ability43 and
temporal gait parameters such as walking speed, stride length and cadence65, 67, with this,
weakness appears to be a key contributing factor to gait deviations observed in CP.
Similar to typically developing children68, muscles at the ankle (ankle plantar flexors) and the
hip (including the hip flexors) joints provide approximately 90% of the mechanical power
generated for forward propulsion throughout gait in individuals with CP64. However, the
literature has observed a general shift in power generation from the ankle to the hip joint
23
during gait, with children with CP adopting a more ‘hip’ driven pattern of locomotion rather
than an ankle driven pattern64,
69, 70
. Numerous studies have displayed inadequate power
production in the affected lower extremities of children with CP, particularly in the ankle
plantar-flexor and knee extensor muscles50, 64, 71. Dallmeijer and Colleagues (2011)71 reported
that peak ankle power to be reduced by more than 40% in CP compared to normative values
for typically developing children71, whilst Rose and McGill (1998)50 reported individuals with CP
to have 50% less ankle power during push-off when compared with age-matched controls50.
This is supported with Engsberg and Colleagues (2000)37 finding that children with CP were
significantly weaker in both dorsi flexors and plantar flexors37. With inadequate muscular
power50, 64, 71, children with CP are likely to experience difficulties in functional tasks.
2.2.2 ACTIVITY AND PARTICIPATION
The ‘functioning and disability’ component of the ICF also comprises activity and participation,
where activity refers to the execution of a task or activity by an individual and participation
refers to ones involvement in life situations10. As well as motor disturbances, children with CP
are at risk of experiencing participation restrictions67, reduced participation in active-physical
activities72-74, greater activity limitations and are considered to be less physically active then
their typically developing peers74, 75.
2.2.2.1 ACTIVITY
Literature consistently reports lower levels of activity for children with CP74-78. Maher and
Colleagues (2007)74 using the Physical Activity Questionnaire found that the level of selfreported physical activity was lower for adolescents with CP when compared to their typically
developing peers74. Bjornson and Colleagues (2007)76 reported that children with CP to be
active only 40.2% of the time, compared with 49.6% displayed in typically developing
children76. Similar to this, Van Zelst and Colleagues (2006)75 reported children with hemiplegic
CP experience significantly lower motor and process skills, using the Assessment of Motor and
Process Skills which may impact on their levels of physical activity75. It has been shown that as
the level of functional walking declines (as the GMFCS level increases), daily walking activity
and percentage of time the child is active also decreases76. As assessed by the Six Minute Walk
Test (6MWT); Calley and Colleagues (2012)78 found children with CP to experience more
limitations across longer distances when compared to their typically developing peers78.
Although the two concepts are closely linked, it is important to recognize them as separate
24
constructs that together with body structures and function and environmental factors all
impact upon an individuals’ quality of life10.
2.2.2.2 PARTICIPATION
Having a positive influence on the development of skills and competence, social relationships,
and long-term mental and physical health, participation in day-to-day formal and informal
activities is vital for children79, 80. Children and youth with physical disabilities are at risk of
limited participation81. Numerous studies have shown that compared with typically developing
peers, children with CP have difficulties participating in activities across home, school and in
the wider community as a result of restrictions in physical functioning and mobility78, 82-84.
Research comparing the differences in participation at school (using the School Function
Assessment85) reported that children with CP experienced lower levels of participation across
all domains, with the largest difference to be found in the environment of playground/recess,
compared with typically developing children86. Outside of school, as assessed via the Children’s
Assessment of Participation and Enjoyment (CAPE)87, children with CP are reported to
participate less frequently, and in a lower range of activities88. Children with CP also spend
more time using a computer than their typically developing peers, as assessed by the
Frequency of Participation Questionnaire (FPQ)89, 90. The Assessment of Life Habits (LIFE-H)
assesses the way in which the young person accomplishes their life habits at home, at school
and in the wider community, and covers 12 domains of participation; nutrition, fitness,
personal care, communication, housing, mobility, responsibilities, interpersonal relationships,
community life, education, work and recreation. Comparing responses of children with CP and
typically developing children, research by Calley and Colleagues (2012)78 indicated children
with CP experience restrictions in their participation across all domains with the exception of
relationships and work78. This was similar to work by Lepage and Colleagues (1999)91, reporting
significant limitations within the recreation, community and personal care domains91. The
cause of the reported limitations in participation and activities, like most aspects of CP, are
likely to stem from a multitude of factors.
As children approach adolescence, with growth, there appears to be an increased tendency
towards muscle tightness, bony mal-alignment and weakness in the antigravity muscles92. This
is followed by the appearance of muscular contractures and an increasing disuse of affected
limbs that in turn exacerbates weakness. Since many children with CP are considered to be less
25
actively mobile than typically developing children, it is reasonable to assume that the disused
muscles become atrophic compared with normal musculature50, further disadvantaging the
force generating capability of muscle. Maruishi and Colleagues (2001) proposed that activities
of daily living to be independently affected by both muscle strength and spasticity in adults
with CP93. Ferland and Collegues (2011) evaluated the relationship between lower limb muscle
strength and measures of locomotor capacity; they reported hip flexor muscle strength and
ankle plantar flexor concentric muscle strength to be independently and significantly
associated with level ground walking (6MWT94) and stair locomotion capacities95. It can be said
that impairments in body structure and function (muscle strength and spasticity) may be
contributing factors to limitations in activities and social participation experienced by children
with CP26.
2.2.3 CONTEXTUAL FACTORS
The second component of the ICF ‘contextual factors’ is made up of environmental factors and
personal factors. Environmental factors refer to the physical, social and attitudinal
environment in which people conduct their lives, while personal factors refer to one’s
attributes as a person10.
Quality of life (QoL) is defined as; an individual’s subjective perception of their satisfaction
across various domains in life in the context of the culture and value systems in which they live
and in relation to their goals, expectations, standards and concerns96. A multidimensional
notion, QoL is considered in terms of different domains of an individual’s life. A variety of
measures have been developed to assess QoL, either from a health or a disorder related focus.
For example, the disorder specific measure, The Cerebral Palsy Quality of Life Questionnaire
for Children (CP-QoL)97, assesses seven domains of QoL including social well-being and
acceptance, feelings about functioning, participation, and physical health, emotional wellbeing, access to services, pain and feeling about disability and family health97. Literature has
reported children with CP to experience a lower QoL than children who are typically
developing78, 98-100 across all domains, in particular physical and emotional wellbeing98, 99.
Russo and Colleagues (2008)101 found significantly lower scores for children with CP across all
domains of the Pediatric Quality of Life Inventory (PedsQoL)102 except for emotional
functioning, which was reported as equal between the two groups101. This was in contrast to
findings by Bjornson and Colleagues (2008)103 who reported a difference between CP and
26
typically developing children in self reported emotional health using the Child Health
Questionnaire (CHQ104)103. With the exception of reporting a lower QoL in terms of physical
pursuits, Calley and Colleagues (2012)78 also reported children with CP to experience a QoL
similar to their typically developing peers78, however it should be noted that the sample of
children (GMFCS I-II) were highly functional.
Interestingly, at the milder end of the motor spectrum (GMFCS I) children with CP are reported
to show a lower emotional QoL than children with more severe levels of motor impairment
(GMFCS II and III)100. This is consistent with the ‘disability paradox’ whereby children with
milder limitations, who are more likely to attend mainstream schools and spend more time
around children without impairment, may be more aware of the physical differences between
themselves and their typically developing peers105. The ICF provides a holistic framework,
considering activity, participation, and body structures and functions. Enhancing any one of
these components through therapeutic intervention can be viewed as a positive rehabilitation
outcome with the ultimate goal to increase an individual’s overall QoL and life satisfaction106.
2.3 THERAPEUTIC INTERVENTIONS
For the various neuromuscular and musculoskeletal problems associated with CP, it is
considered that most children can benefit from a multitude of different treatments and not
just a single treatment modality3. Because of the complexities in treating a child with CP,
treatment should be determined using a multidisciplinary team approach with clearly outlined
goals3. Gormely (2001) discussed that treatment for impairments present in a child should be
treated not because of their presence, but if they are interfering with some level of
functioning3. As stated previously, spasticity and muscular weakness, two motor impairments
known to impact function, will be the focus of this literature review.
In the broadest terms, the goals of any spasticity treatment plan are to maximise active
function, ease care, and prevent secondary problems such as pain, subluxation, and
contracture107. The range of treatments for spasticity is large, from simple stretching exercises,
to oral and injectable therapies, to surgeries such as, tendon lengthening procedures108,
intrathecal baclofen pumps109 and selective dorsal rhizotomies110. In determining the best
treatment plan, each case is unique. Treatments likely to maximally improve function should
be used, balanced against the risks and cost effectiveness3. BoNT-A has been shown to be
27
effective in reducing spasticity in children with CP111, 112 and will be discussed in further detail
below.
In recent years, the management of muscular weakness has received substantial interest; with
strength training recognised as a key therapeutic intervention113-115. Strength training and its
functional outcomes in the CP population will also be discussed in further detail in this review.
2.3.1 BOTULINUM TOXIN T YPE-A
Botulinum Neurotoxin (BoNT) is a product of the synthesis of the bacterium Clostridium
Botulinum116. It is a potent neurotoxin known to have seven different serotypes with names
assigned as type A through to type G. BoNT-Type A (BoNT-A) is the most commonly utilised
serotype for therapeutic purposes as it has the longest duration of effect117. Following its
injection into muscular tissue BoNT-A acts to inhibit the release of acetylcholine in the
neuromuscular junction, causing partial chemodenervation and muscle relaxation of the
injected muscle118. This effectively acts to paralyse the overactive muscle, a pharmacological
affect that takes peak affect 2 weeks post injection119, 120. However, paralysis of the muscle is
only temporary with re-innervation beginning to take place at three months post injection and
neuronal activity completely returning to normal by six months121-123.
The application of BoNT-A in the management for spasticity is widely accepted and utilised as a
treatment option for individuals with spastic CP124-128. Numerous studies report positive results
of its effectiveness in temporarily treating spasticity112, 123-127, 129-132 and importantly, it is shown
to have an acceptable safety profile129,
133-137
. Muscular injections of BoNT-A for spasticity
presents no hazard for patients, with careful administration and close monitoring of dose
levels that are determined based on body weight, muscle mass and degree of spasticity as per
established guidelines112, 117, 123, 138, 139. The adverse effects of injection are uncommon, mild
and transient140, consisting of the possibility of skin rash, pain on injection, occasionally mild
flu-like symptoms, anaphylaxis, excessive fatigue, and the most common, excessive
weakness122,
129, 141
. Due to the nature of the action of BoNT-A, muscle weakness in the
targeted muscle is to be expected142, 143. In an animal study, Longino and Colleagues(2005)142,
demonstrated that BoNT-A induced muscle weakness in the long term is frequency and muscle
length dependent, with muscle weakness being greater in short compared with long
muscles142. However, muscle weakness in non-targeted neighbouring muscles and antagonist
muscles have also been reported following BoNT-A in animal studies, postulated to be a result
28
of functional limb disuse or the diffusion of BoNT143,
144
. It has also been noted that when
BoNT-A is injected into the hyperactive muscle the induced paresis will produce a reduction of
the diameter of the target muscle and that, if given over a long period of time, may result in
real muscle atrophy116.
Recent publications have raised concern regarding the effect of BoNT-A on muscle size and
morphology145,
146
. Schroeder and Colleagues (2009)146 measured neurogenic atrophy in the
injected medial gastrocnemius in two healthy adults post BoNT-A; with a reduction of 14-19%
in cross sectional area after 3 months, and reductions still seen at 6, 9 and 12 months post
BoNT-A, whilst there were no changes in the contralateral placebo injected muscle. Dunn and
Colleagues (2010)147 supplemented this finding with reports of prolonged denervation of
BoNT-A injected muscles up to 5 months post injection. Rare reports in the cosmetic industry
provides us with some observable examples for BoNT-A related atrophy, with its use in facial
contouring for reducing masseter muscle thickness148, 149, and its use in reduction of muscle
size in women’s legs in the desire to appear more aesthetically appealing150. Animal studies
have also revealed BoNT-A’s effect on muscle; Fortuna and Colleagues (2011) 151 compared the
injected limbs to non-injected limbs of rabbits to find reductions in muscle mass of up to 50%
injected muscles 1month after injection, Ma and Colleagues (2004)152, found muscle mass in
injected limbs in rats to be reduced by 32% of the control side 2 weeks after the injection, with
reduction of 24% still evident at 3months post. Despite these reports, the potential effect of
atrophy as a muscular response to BoNT-A treatment is yet to be investigated in abnormal
muscles such as that of CP. Despite this concern, functional outcomes of BoNT-A remain
positive. Molenaers and Colleagues (2010)153 concluded that, when applied according to an
integrated approach and started at a young age, BoNT-A treatment has the potential to
improve the overall function of children with CP153.
2.3.2 FUNCTIONAL OUTCOMES OF BONT-A
2.3.2.1 AT THE LEVEL OF BODY FUNCTION AND STRUCTURE
Along with the benefits of reduced muscle tone154, BoNT-A therapy also provides pain relief116
and improvements in range of joint motion154, 155. With the spasticity treatment often allowing
the child the opportunity to learn specific targeted movement patterns otherwise restricted to
them, improvements are also reported in functional measures156-160, in motor skill abilities161,
162
and in gait154. Also a result of the reduction of spasticity, improvements in walking gait
following BoNT-A are reported in both kinematics (dynamic range of joint) and kinetics (joint
29
moments and power generation)15,
dorsiflexion166,
168, 169
123,
163-167
. More specifically, increases in ankle
, knee extension at initial contact166, and a normalisation of ankle
kinetics166 during gait can be expected. Zurcher and Colleagues (2001)166 evaluated kinetics at
the ankle during gait and reported an increase in power after BoNT-A injections in children
with CP. In contrast with these reports, Maanum and Colleagues (2011)170 did not find any
clinically relevant effects of BoNT-A on predefined kinematic variables in a population of adults
with spastic CP170. However, they concluded their results to reflect relatively fixed gait
strategies in adults with spastic CP, with co-existing other impairments, such as contractures,
muscle weakness and reduced motor control and balance170. With this in mind, reducing
muscle tone alone may not be enough to change joint angles during gait170-173.
In treating dynamic equinus, BoNT-A works to prevent gastrocnemius shortening, and acts to
avert fixed deformities, from a long term perspective, this can defer the need for orthopaedic
surgery127,
154
. The use of BoNT-A in the CP population results in improvements in body
structures and functions156, 157, 163, 174, 175. A recent systematic review of the literature uncovered
a focus on the effects of BoNT-A on body structure and function measures, as well as gait
analysis parameters, in the studies of BoNT-A use in CP176. Baird and Colleagues (2010)176
explained that measures for this domain are most proximate to the intervention, therefore are
most likely to manifest changes176, however it is still important to understand the effect of
BoNT-A treatment at the levels of activity and participation.
2.3.2.2 AT THE LEVEL OF ACTIVITY AND PARTICIPATION
It is considered that the positive effect of BoNT-A therapy on gross motor function or gait may
extend to concomitant improvements in activity and participation. However, despite the
wealth of research investigating the effect of BoNT-A on the body structures and function, very
few studies have evaluated its effectiveness on functionality with respect to activity and
participation measures. In an adult population with spastic CP, activity was demonstrated to
improve following BoNT-A, assessed by the Timed Up and Go (TUG), compared with a placebo
group170. Within children, a study by Bjornson and Colleagues (2007), reported differences in
activity domains (GMFM-66 and GMFM-88, COPM) but demonstrated no differences on the
effect of BoNT-A in the participation domain using the COPM satisfaction scores and the Goal
Attainment Scale15. Wright and Colleagues (2008)163 also indicated improvements in measures
of activity (assessed by the GMFM and the Pediatric Evaluation of disability inventory), as well
as in participation (the Pediatric Outcomes Data Collection Instrument) alongside reductions in
30
measures of body functions and structures163. These reports indicate that BoNT-A treatment
can have an effect on daily activities130, however information is sparse on the effect on
participation177,
178
. Outcomes within the activity and participation domains are of great
interest, however they may represent secondary and tertiary effects of BoNT-A176, this may
explain the paucity of research in this area.
2.3.2.3 AT THE LEVEL OF CONTEXTUAL FACTORS
Of the effect of BoNT-A on a child’s QoL, literature is sparse. Research investigating the healthrelated quality of life (HRQoL, using the Short Form-36) found no change following BoNT-A in
the lower limbs of adults with spastic CP170 or in the upper limbs of children with hemiplegic
CP179. In contrast to this, a population of adults with upper motor neuron lesions (e.g. stroke or
CP) did report improvements in perceived health-related QoL following BoNT-A treatment and
physical intervention (physical therapies, orthoses, orthopaedic shoes and footwear
correction)180. A study by Coutinho dos Santos and Colleagues (2011)181 utilised two measures,
the Pediatric Outcomes Data Collection Instrument (PODCI) and the Child Caregiver
Questionnaire (CCQ) to show improvements in QoL in children with CP a year after BoNT-A,
however no inclusion of a control group limits these results181. In the hemiplegic CP
population, Russo and Colleagues (2007)182 reported improvements in self worth, but not in
QoL (using the Pediatric Quality of Life Inventory)182. QoL may depend on multiple factors that
may or may not necessarily be influenced by the intervention182; as for activity and
participation, more research is needed to improve our understanding of the complete
functional effect of BoNT-A on CP.
2.3.3 STRENGTH TRAINING
Strength training is defined as a method of improving muscular strength by gradually
increasing the ability to resist force through the use of free weights, machines, or the person's
own body weight183. The terms strength training and resistance training are often used
synonymously, with resistance training generally a broader term, defined as a specialised
method of conditioning, which involves the progressive use of a wide range of resistive loads
and a variety of training modalities designed to enhance health, fitness, and sports
performance”184.
With the major focus on spasticity management in CP, early concerns that any excessive force
would lead to an increase in spasticity meant that resistance training was avoided for children
31
with spastic CP185. However, with weakness gaining more recognition as a significant
impairment in CP, recent literature has turned its interest towards strengthening the
muscles113-115. Ross and Engsberg (2002)39 stated that strengthening muscles in individuals with
CP should become a treatment priority, after reporting that muscle weakness was consistent in
CP whereas spasticity was not39. A further endorsement is that to date there is no empirical
evidence of strength-training increasing spasticity or contractures in people with CP46, 177, 186-190.
A growing number of studies have confirmed that individuals with CP can have significant
strength improvements following effective strength-training programs44-46, 65, 187-196. However
contrary to previous systematic reviews114,
115, 197-199
, Scianni and Colleagues (2009)200
controversially suggested strength training to be neither effective nor worthwhile in children
and adolescents with the CP. This review brought into question, again, the future of strength
training in the CP population201-203. However responders were quick to critique areas of
concern within this review. Scianni restricted the reviewed research to randomised controlled
trials (RCT’s); whilst it is agreed upon that more rigorously conducted studies are needed201, by
only including RCT’s it was felt that this review excluded important evidence from uncontrolled
trials while including evidence from randomised controlled trials of poor quality201. The
unusual mixture of interventions in the review by Scianni is also queried, with the analysis of
three different modes of intervention (electrical stimulation, progressive resistance exercise
training, endurance training) within one meta-analysis202,
203
. Questions were raised about
whether the interventions were applied with sufficient intensity to increase muscle strength203,
in particular, the inclusion of two studies that used electrical stimulation as the sole
intervention
204, 205
and a loaded sit-to-stand study192. However, this review is in agreement
that there is a concerning lack of appropriate intervention protocols for strength training in
children with CP200, 201, 203, 206. Verschuren and Colleagues (2011)206 stated that research is yet to
determine the most effective protocol for improving strength in the CP population206.
As a guide, the key elements that should be included in a strength training program are: i)
sufficient resistance so that only a relatively small number of repetitions (usually less than 12)
can be completed before fatigue; ii) resistance is progressed as strength increases, and iii) the
program runs for a sufficient time (usually a minimum of six weeks) for the benefits to
accrue115, 207. However, amongst research investigating the effects of strength training in the
CP population, there is noticeable variability in the parameters of training programs being
administered; differing in the type of equipment, the exercise details, the duration and
intensity of the program115. Strength programs include the use of body weighted exercises,
32
free weights, and strength training machines. Programs have varied in duration from four190,
six44, 65, 187, 188, 208, 209, eight46, 210, ten189, 211, 212 and 12 weeks191, 195, but typically each frequented
three times per week.
With strength-training interventions involving effort against progressive resistance, the
amount of resistance has varied throughout research from 65%44,
65, 188, 213, 214
, 70%189 and
80%193, 208 of one repetition maximum, (i.e. the maximum weight the participant could lift in
one repetition), to using the maximum load that the child could manage for the required
number of repetitions before fatiguing187, 195, 196, 212, 215. However despite the variability in the
loading, each study incorporated an element of progression throughout their programs, in
either the load weight or in the number of repetitions. At this stage more research is needed
to specifically determine the type, intensity, duration and the intervals of rest206 for training
muscle strength in children with CP. However until specific guidelines have been set for the CP
population, Verschuren and Colleagues (2011)206 encourage clinicians to refer to the National
Strength and Conditioning Association (NSCA) guidelines for resistance training for children
who are developing typically184 (Table 1).
Table 1 General youth resistance training guidelines as set by the National Strength and
Conditioning Association184. * 1 RM= 1 Repetition Maximum.
Variables of resistance training
NSCA guidelines
Warm up
Intensity/volume
5–10 minutes of dynamic activities
Single-joint and multi-joint exercises utilizing concentric and
eccentric contractions
1–3 sets of 6–15 repetitions of 50%–85% of 1 RM*
Rest intervals
1–3 minutes
Frequency
2–4 times a week on non-consecutive days
Duration
8–20 weeks
Progression
Increase resistance gradually (5%–10%) as strength improves
Age
Age 7 years and older
Type
2.3.4 FUNCTIONAL OUTCOMES OF STRENGTH TRAINING
2.3.4.1 AT THE LEVEL OF BODY STRUCTURES AND FUNCTION
There is strong evidence supporting the view that strength training can increase the ability to
generate muscle force in people with CP44-46, 65, 187-196. Adding value to this is that the strength
gains are reported to be similar to those experienced by the non- CP population following
33
training45, 46 and can be maintained over a period of time following the cessation of strength
training 46, 188, 190, 212, 216. Research has documented that following strength training people with
CP can achieve significant strength improvements that are translatable to gains in motor
function46, 65, 115. Such gains have included flexibility, posture and balance177, with stable194, 217,
211
or increased ROM at the knee194, 217, improvements relating to walking46, 65, 115, 193, 210, 213,
with increase in muscle strength considered one of the major factors of gait function196.
Using three dimensional gait analysis (3DGA), literature has measured improvements in some
gait parameters, although this was not always statistically significant44, 65, 193, 210, 213. Following
strengthening, changes in kinematics have been demonstrated including; a more upright
posture210, decrease in crouch210, 213, 193, improved hip and knee extension through stance193, 215,
improved knee extension in late swing213, and trends of improved ankle dorsi-flexion at swing
and initial contact193. These are particularly pertinent outcomes, with excessive hip and knee
flexion common features observed in CP that will only worsen without intervention218.
During typical gait, the ankle plantar-flexors act as the greatest contributors to forward
propulsion, vital for a normal gait pattern219. Eek and Colleagues (2011)69 reported a
relationship between muscle strength (weakness) and gait pattern, seen in particular in kinetic
variables at the ankle, but also surmised that adequate strength around the hip and knee joints
are needed for stability to allow plantar-flexor power generation at push off69. However, few
studies that implemented 3DGA have reported kinetic alterations following strengthening.
Engsberg and Colleagues (2006)193 report inconclusive kinetic alterations following strength
training and suggested that future research should include the calculation of power. Power is
defined as the work performed per unit of time and may be used to document the net energy
generation or absorption of the muscles during activity31. Strengthening of the muscles is more
likely to result in changes in the muscles force generating capacity than to alter kinematic
profiles, therefore, investigating power throughout the gait cycle may be a more revealing
method of evaluating the effect of strength training on gait. Improvements in recruitment and
muscle activation are possible contributors to the improved gait patterns following strength
training193,
210,
213
, however, with muscle strength associated with hypertrophy212,
improvements in muscle morphology may also be a potential factor.
Hypertrophy is thought to result from the increase in individual muscle fibre size – which can
contribute to increases in muscle mass, cross sectional area and volume, with associated
34
increases in muscle strength220. In the typically developing population, research has shown
increase in muscle volume up to 14% in the knee extensors of adult’s males, and up to 11% in
the elderly following strengthening221, 222. It is thought that within the first 3 to 5 weeks of
progressive strength training improved neural activation is responsible for the major portion of
strength gained, however after this time, increases in muscle strength are primarily due to
hypetrophy223. Therefore, to increase the size of healthy muscle, a prolonged period of
progressive strength training is required. To date, the effect of strength training on muscle
volume in children with spastic CP has only been investigated in one study; McNee and
Colleagues (2009)212 reported that alongside improvements in plantar flexor strength,
gastrocnemius muscles also increased in volume up to 17% after 5 weeks and up to 23% after
10 weeks of strength training in children with CP. McNee’s research indicates that strength
training could amend the pre-existing muscle size and muscle strength deficit that is commonly
present in CP212.
Literature reporting functional outcomes such as walking ability has mixed results. The GMFM
is a common measure used in studies reporting the effect of strength training on functional
changes; following strength-training programs targeting muscles of the lower limb
improvements have been significant in Dimension E65,188,192, 193, 224, relating to walking, running
and jumping. However this did not reach statistical significance for some studies187,
225
.
Similarly, whilst some studies show significant improvements in walking velocity65, 193, 208, 224,
others do not44,
46, 190, 210, 213
. Whilst the effect of strength training on body structure and
functions is generally positive, it remains undecided whether strength training is effective in
improving activity or participation.
2.3.4.2 AT THE LEVEL OF ACTIVITY AND PARTICIPATION
Little information is available on the effects of strength training on the participation dimension
of functioning and disability115. McBurney and Collegues (2003)177 demonstrated qualitative
examples of children increasing participation in school, leisure, social and family events after
undertaking a home based strength program, in agreement, Darrah and Colleagues (1999)211
provided anecdotal support for increased participation in children with CP after completing a
community fitness program of aerobics, strength training, and stretching211. Quantitative
measures of participation as an outcome of strength training are rare115. Scholtes and
Colleagues (2012)226 utilised the Children’s Assessment of Participation and Enjoyment (CAPE)
questionnaire to measure participation following a 12 week strength training program in
children with CP, and subsequently found no effect226.
35
Possible explanations for this mixture of results are; the relatively short training periods
administered in the studies (i.e., 4–8 weeks), the diversity in the type of training (e.g., home or
school-based, and functional or non-functional training regimes), and insufficient training
resistance or progressions226.
Scholtes and Colleagues (2012)191 responded to these reports with a 12-week functional
progressive resistance training program which followed appropriate guidelines184 and despite
resulting in significant increases in muscle strength (by up to 14%)191, there was no carry over
effect to walking ability (as assessed by the Timed 10-Meter Walk Test, 1Minute Fast Walk
Test, and the Timed Stair Test) or participation226. The conclusion was in agreement with
Antilla and Colleagues (2008)199 systematic review that stated strength training does not
improve walking speed and stride length in children with CP199, with the contention that in
order for a domain such as walking ability to be improved, task specific interventions, such as a
specific ambulation programs are recommended226 rather than a strength program.
2.3.4.3 AT THE LEVEL OF CONTEXTUAL FACTORS
To our knowledge, only two studies have examined the effect of strength training on QoL in
children with CP. Engsberg and Colleagues (2006)193 reported significant improvements in
QoL193, whilst Verschuren and Colleagues’ (2007)178 results also demonstrated a positive
impact of strength training on QoL178. However, neither measure used for assessing QoL were
condition specific (the Pediatric Quality of Life Inventory and the Children’s Health-Related
Quality of Life)178, 193, and therefore may not be as relevant to a child with CP and the issues
pertinent to their QoL. Despite the paucity of research in this area, contextual factors are an
important aspect to consider in the assessment of strength training. However, Tsoi and
Colleagues (2012)227 suggested that if improvements in QoL are to be expected in the
management of CP, there is a need for comprehensive treatment approaches, targeted not
just the impairment but the loss of function227.
2.4 THE NEXT STEP IN CP THERAPY
CP is a disability that by its very definition, involves an extensive range and combination of
neuromotor and musculoskeletal problems and associated conditions2. In the clinical setting, it
is inconceivable to treat just one motor impairment and expect remarkable improvements in
overall function. Therapeutic interventions need to consider more than one impairment of CP
36
if improvements in levels of activity and participation are sought114, and is a logical direction
for maximising functional outcomes.
The combination of therapies is already somewhat in practice for the CP population; however
only recently does the literature appear to formally investigate this. Clinicians need practical
evidence, and guidelines to direct evidence based care. Spasticity management with BoNT-A is
a commonly used treatment option for children with CP; it is suggested that the reduction in
spasticity through BoNT-A treatment may ease the ability to move, and clinicians frequently
utilise this time period (of reduced spasticity) to administer complimentary interventions to
potentiate the effect of the BoNT-A for spasticity reduction127,228 such as stretching, range of
motion exercise, serial casting, splinting/orthotics and motor training229. Literature has
consistently emphasised the importance of physical therapy combined with BoNT-A
treatment34, 154, 157, 172, 230 and functional outcomes have been positive. For example, Scholtes
and Colleagues (2007)172 demonstrated that comprehensive rehabilitation, administered in
combination with multilevel BoNT-A successfully improved knee extension during gait,
increased muscle length, and decreased spasticity172. A systematic review indicated that trials
favoured BoNT-A with usual care or physiotherapy over usual care or physiotherapy alone,
however due to modest methodological quality neither treatment method could be
definitively recommended231. Occupational therapy has also been administered in combination
with upper limb BoNT-A therapy, and has successfully demonstrated a significant reduction in
muscle tone, whilst at the same time achieving an accelerated attainment of functional
goals232, improvements in body structure, activity participation, and self-perception in children
with CP182.
Muscular weakness and spasticity are concurrent impairments of a CP, with neither the only
cause of the motor dysfunction in CP, therefore, it is reasonable to state that alleviating only
one of the symptoms will have only partial effect on the improvement of motor function233.
With this in mind, it seems a logical step to target both spasticity and muscular weakness in
combination.A recent pilot study by Elvrum and Colleagues (2012)234 investigated the
combination of resistance training and BoNT-A in the hand234. Their results demonstrated that
the addition of eight weeks resistance training strengthened non injected muscles temporarily
without a concomitant systematic increase in muscle tone234. Furthermore, the resistance
training may have reduced the short-term strength loss that results from BoNT-A injections in
the spastic muscles, and it was suggested that additional resistance training may have also
increased active range of motion to a larger extent than BoNT-A alone234. However, the
37
combination of therapies was not successful in improving hand and arm use over and above
BoNT-A treatment alone; and it was concluded that more task-related resistance training may
be required234.
In addition to this, a pilot study by Bandholm and Colleagues (2012)195 included progressive
resistance training to their physical rehabilitation program following BoNT-A treatment of the
ankle plantar flexors195. This study resulted in increases in the maximal torque-generating
capabilities of the plantar flexors, with a simultaneous reduction in plantar flexor spasticity,
and a trend of increased function195. These two pilot studies are the first indications of a
formal combination of BoNT-A and strength training within the literature, and highlights the
potential for future therapy.
2.5 SUMMARY
CP describes a group of disorders that encompass a wide variety of musculoskeletal problems,
and secondary conditions2. Spasticity, weakness, dystonia, muscle contractures, bony
deformities, in-coordination and loss of selective motor control are amongst the list of possible
motor impairments associated with CP, affecting function3. The ICF promotes a broad
application of outcome measures that ensures a multidimensional evaluation of functioning,
and of therapeutic interventions11, 14, and is the ideal tool to further understand the effects of
interventions in the lives of children with CP.
Spasticity26 and muscular weakness36,
37-39, 236
are two key motor impairments of CP; both
significantly affecting function27, 28. Particular attention throughout the literature pertains to
walking, with the presence of spasticity typified by different alterations of gait29. However,
whilst it is important to note spasticity is a significant impacting factor on deviations of gait
frequently associated with CP, other factors are also influential; such as the development of
contractions, poor selective motor control and muscular weakness29. Muscular weakness is
increasingly considered as a significant motor impairment of CP36, 37-39, 236. Attributable to both
neural mechanisms and muscle tissue changes36, the literature has demonstrated that children
with CP have smaller muscles then their typically developing peers52, 57-60. Muscle strength is
positively associated with walking ability43, with muscle weakness potentially linked with gait
deviations50, 64, 71. Children with CP are reported to experience lower levels of activity74-78, are
38
at a higher risk of limited participation81, and experience a lower QoL than children who are
typically developing78, 98-100.
The application of BoNT-A in the management for spasticity is widely accepted and utilised as a
treatment option for spasticity for individuals with CP124-128. Numerous studies report positive
results of its effectiveness in temporarily treating spasticity112, 123, 126, 127, 129, 130, 160. However,
recent literature has reported a potential for post BoNT-A weakness122, 129, 141 and atrophy146,
147
. This is of particular concern for a population of children already predisposed to muscular
weakness38, and smaller muscles57. Despite the concern, there is a paucity of research
investigating the effect of BoNT-A on the muscle morphology and strength of children with CP.
Of the ICF, at the level of body structures and functions, the use of BoNT-A in the CP
population is encouraging156, 157, 163, 174, 175. As well as indications of functional improvement156160
, literature indicates a positive effect of BoNT-A on gait patterns154, 166. The effect of BoNT-A,
however has not been researched to a large extent at other levels of the ICF; reports indicate
that BoNT-A treatment can have a positive effect on daily activities130, however information is
sparse and inconclusive on the effect on participation177, 178 and QoL170, 179.
Targeting muscular weakness, a growing number of studies have confirmed that individuals
with CP can achieve significant strength improvements following effective strength-training
programs44-46, 65, 187-196. In addition to strength gains, literature suggests improvements relating
to walking46,
65, 115, 193, 210, 213
. Whilst only one study has investigated the potential for
hypertrophy in the CP population212, this evidence is positive, indicating that strength training
could amend the pre-existing muscle size and muscle strength deficit common in CP212. Whilst
the effect of strength training on body structure and functions is generally positive, it remains
to be determined whether strength training is effective in improving activity or participation.
In addition to this, there is also a paucity of research pertaining to QoL in relation to strength
training in the CP population. The application of outcome measures at all levels of the ICF is
recommended for comprehensive evaluations of therapeutic treatments. In this regard,
current research is limited on the comprehensive effects of two common interventions for
children with CP, BoNT-A and strength training, hence more research is needed.
In terms of the body structures and function dimension of the ICF, the effectiveness of BoNT-A
for spasticity management and strength training for muscular weakness is evident throughout
the literature. The next, logical progression is to combine both therapy options, in an aim to
achieve optimal functional outcomes for children with CP, which may impact across all levels
of the ICF.
39
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postoperative strength-training program on the walking ability of children with cerebral palsy:
A randomized controlled trial. Arch Phys Med Rehab. 2006;87:619-26.
226.
Scholtes VA, Becher JG, Janssen-Potten YJ, Dekkers H, Smallenbroek L, Dallmeijer AJ.
Effectiveness of functional progressive resistance exercise training on walking ability in
children with cerebral palsy: A randomized controlled trial. Res Dev Disabil. 2012;33:181-8.
227.
Tsoi WSE, Zhang LA, Wang WY, Tsang KL, Lo SK. Improving quality of life of children
with cerebral palsy: a systematic review of clinical trials. Child Care Health Dev. 2012;38:21-31.
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228.
Boyd R, Graham H. Botulinum toxin A in the management of children with cerebral
palsy: indications and outcome. Eur J Neurol. 1997;4:15-22.
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Goldstein E. Spasticity management: an overview. J Child Neurol. 2001;16:16-23.
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Leach J. Children undergoing treatment with Botulinum toxin: the role of the physical
therapist. Muscle Nerve. 1997;6:194-207.
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Ryll U, Bastiaenen C, De Bie R, Staal B. Effects of leg muscle botulinum toxin A
injections on walking in children with spasticity-related cerebral palsy: a systematic review.
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Wallen M, O'Flaherty S, Waugh M. Functional outcomes of intramuscular botulinum
toxin type A and occupational therapy in the upper limbs of children with cerebral palsy: a
randomised controlled trial. Arch Phys Med Rehab. 2007;8:1-10.
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secondary conditions for children with Cerebral Palsy: section on pediatrics research summit
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Elvrum A-K, Braendvik S, Saether R, Lamvik T, Vereijken B, Roeleveld K. Effectiveness of
resistance training in combination with botulinum toxin-A on hand and arm use in children
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treatment of children with cerebral palsy. J Neurosurg. 2006;105:8-15.
57
CHAPTER THREE
MORPHOLOGICAL ALTERATIONS IN SPASTIC MUSCLES IMMEDIATELY
FOLLOWING BOTULINUM NEUROTOXIN TYPE-A TREATMENT IN CHILDREN
WITH CEREBRAL PALSY.
This manuscript was submitted for publication into Muscle and Nerve in December, 2012 and
is currently under review.
Williams SA, Reid SL, Elliott CM, Shipman P, Valentine J. Morphological alterations in spastic
muscles immediately following Botulinum Toxin Type-A treatment in children with Cerebral
Palsy. Muscle and Nerve. 2012 (In Review)
The PhD candidate, Sîan A Williams, accounted for 80% of the intellectual property associated
with the final manuscript. Collectively, the remaining authors contributed 20%.
58
FOREWORD
BoNT-A is widely accepted and utilised as an established treatment option for spasticity
management for individuals with CP. There are some concerns that whilst children appear to
do well functionally with the use of BoNT-A, there is evidence for an atrophic effect of BoNT-A
documented in typically developing muscles in human and animal research. To the authors
knowledge this has not yet been investigated in pathological muscles. This first paper
presented in this thesis has investigated the effect of BoNT-A on muscle morphology, muscle
strength and functional ability in children with CP, and in doing so presents the first known
documentation of the morphologic alterations of pathological muscles in response to BoNT-A.
This new information presents implications for future research, which in turn may guide future
treatment plans for the use of BoNT-A in spasticity management.
59
3.1 ABSTRACT
Aim: To investigate the morphological alterations of muscles of the lower limbs in children
with CP following Botulinum Toxin Type-A (BoNT-A) treatment.
Method: Fifteen children, aged 5-12 years (x=8years 5mo, SD 1yr 10mo) with CP receiving
BoNT-A for spasticity management were included. Muscle morphology was assessed using
Magnetic Resonance Imaging and Mimics software. Strength was assessed using dynamometry
and functional measures included the Timed-Up-and-Go and the 6-Minute Walk Test.
Assessments were timed 2weeks prior to and 5 weeks post injection.
Results: Whilst total muscle group morphology of the injected muscle group remained
unchanged, individual muscle alterations were evident. A 4.47% decrease in the injected
gastrocnemius muscle volume (MV) was statistically significant, (p=0.006) as was a 3.96%
increase in soleus MV (p=0.020) following BoNT-A. Injected medial hamstrings MV decreased
by 5.85%, approaching statistical significance (p=.076).There were no statistically significant
changes in strength or function (p<.05).
Interpretation: MV decreases were observed in the injected muscle, with synergistic muscle
hypertrophy that appeared to compensate for this decrement. The 4-5% decreases in BoNT-A
injected muscles are not dramatic comparative to reports in recent animal studies. This is a
positive indication for BoNT-A, particularly as it also did not negatively alter function.
60
3.2 INTRODUCTION
Spasticity, muscle weakness and muscle co-contraction are common motor problems
associated with Cerebral Palsy (CP). Botulinum toxin (BoNT-A) is widely used for the
management of spasticity in children with CP1, 2. As well as its respectable safety profile3-5, the
literature describes many positive outcomes from BoNT-A treatment including; a reduction in
muscle tone6, increase in joint range of
motion6, improved gait patterns6, functional
improvements7, 8 and delayed and reduced requirement for surgical interventions to treat
musculoskeletal deformities when combined with conservative treatments9. However,
generalised muscle weakness5, 10, 11 and weakness in neighbouring non-targeted muscles12, 13
have been reported as undesirable effects of BoNT-A.
There have been recent publications raising concern regarding the effect of BoNT-A on muscle
size and morphology14,
15
. Schroeder et al.,(2009)15 measured neurogenic atrophy in the
injected lateral gastrocnemius in two healthy adults post BoNT-A; with a reduction of 14-19%
in cross sectional area after 3months, and reductions still seen at 6,9 and 12 months post
BoNT-A, there were no changes in the contralateral placebo injected muscle. Dunne et al.,
(2010)16 supplemented this finding with reports of prolonged denervation of BoNT-A injected
muscles up to 5months post injection. Rare reports in the cosmetic industry provides us with
some observable examples for BoNT-A related atrophy, with its use in facial contouring for
reducing masseter muscle thickness17, 18, and its use in reduction of muscle size in women’s
legs in the desire to appear more aesthetically appealing19. Animal studies have also revealed
BoNT-A’s effect on muscle; Fortuna et al.,(2011) 13 compared the injected limbs to non-injected
limbs of rabbits to find reductions in muscle mass of up to 50% injected muscles 1month after
injection, Ma et al.(2004)20, found muscle mass in injected limb in rats to reduced by 32% of
the control side 2 weeks after the injection, and still to be reduced by 24% at 3months post.
Considering the repeated use of BoNT-A to treat spasticity in children with CP, it is necessary
to understand the impact of this treatment in this population, particularly with regard to
muscle function and structure.
It is well recognised that muscle structure and size is associated with muscle strength in the
adult and adolescent population21, 22. Children with CP have also been shown to have smaller
and weaker muscles23. Over the last decade weakness has been increasingly recognised as a
significant motor impairment22-24 purportedly affecting the functional ability in children with
CP25, 26. A recent review of the literature in spastic CP found consistent evidence for small
61
muscle size as indicated by reduced muscle volume, cross sectional area, thickness and belly
length in comparisons of paretic muscles with non-paretic and typically developing muscles24.
Barber et al.(2009)25 has described volumetric deficits in the medial gastrocnemii of young
children (2–5y) with spastic CP of 22% compared with typically developing children. For a
population already predisposed to decrements in muscle size and strength, a treatment that
potentially leads to further atrophy and weakening of the muscle should be well understood.
The concern is that whilst children appear to do functionally well with the use of BoNT-A, there
is evidence for an atrophic effect of BoNT-A documented in typically developing muscles in
human and animal research that, to the authors knowledge, has not yet been investigated in
pathological muscles. This research is the first to investigate the immediate morphological
alterations in muscles of the lower limbs of children with CP following BoNT-A treatment for
spasticity management. To report the comprehensive effect if the neurotoxin, we report the
alterations of the injected, synergist and antagonist muscles to the BoNT-A, and include
measures of strength and functional ability. It was hypothesised that the injected muscle
would display a reduction in muscle morphology (volume) which could also result in a reduced
strength capacity.
3.3 METHODS
3.3.1 PARTICIPANTS
Ten boys and five girls with spastic diplegic CP classified as Gross Motor Function Classification
System (GMFCS) level of I-II were recruited via the spasticity management service at Princess
Margaret Hospital (PMH) in Perth, Australia. The children ranged from 5-12years, mean age of
8years 5mo (SD 1yr 10 mo, range 5-11yrs), an average height of 129.87cm (SD 10.92cm),
weight of 27.97kg (SD 7.43kg) and BMI of 16.34 (SD 2.4). No child had undergone serial casting
in the previous six months and no child a history of lower limb surgery. Informed written
consent was obtained from the parents of all the participants. Ethical approval for the study
was obtained from the Ethics Committee of PMH (1766), and from the University of Western
Australia.
Spasticity was assessed bilaterally using the Modified Ashworth Scale (MAS)26 by the same
assessor, blinded to timing of BoNT-A . All 15 children were receiving BoNT-A treatment for
spasticity management bilaterally in their lower limbs, and had already received a minimum of
62
two series of BoNT-A prior to the injection series included in the study (maximum series=15,
mean series=8.93). The muscle(s) selected for injection were determined by clinical
assessment and functional goals, the total dose of BoNT-A (Botox®, Allergan, Irvine, CA, USA)
was empirically selected for each muscle, and injections were guided by ultrasound. All
participants received BoNT-A to bilateral gastrocnemius' (30 legs injected; 2-6U/kg), and five
participants also received BoNT-A to bilateral medial hamstrings (10 legs; 2-4U/kg). Other
muscles injected included the soleus (4legs; 1-2U/kg) adductors (2 legs; 1U/Kg), rectus femoris
(2 legs; 1U/Kg), and tibialis posterior (1 leg; 1U/Kg). No child had more than three muscles
injected per leg.
Of the five children who received BoNT-A to both the medial hamstrings and the
gastrocnemius, the mean age was 7yrs, 10mo (SD 2yrs, 7mo), three were classified as GMFCS I
and two GMFCS II.
3.3.2 PROCEDURES
The study was a single group repeated measures design. Children completed two assessments;
1) timed approximately 2 weeks prior to their scheduled BoNT-A (PRE) & 2) on average 5
weeks (SD 1week, range 3-6weeks) post injection (POST).
3.3.2.1 MUSCLE MORPHOLOGY
Muscle Morphology (muscle volume (MV)) of the lower limbs was assessed using Magnetic
Resonance Imaging (MRI). Efforts were made to standardise the time of day that each
participant completed their scan. Axial spin-echoT1-weighted MR images were acquired
bilaterally from the level of the ankle malleoli to the iliac crest while subjects lay prone in a
1.5T whole body MR unit (Magnetom Sonata Maestro Class, Siemens Medical Solutions,
Erlangen, Germany). Subjects were positioned in neutral hip rotation, maintained passively
using standard patient positioning with foam pads. Images of the thigh and lower leg were
collected using a repetition time of 572ms, echo time of 13ms, slice thickness of 5mm, and
mean inter-slice gap between 5-7mm. A matrix size of 256×160mm was used for all thigh
scans, and 256x144 for lower leg, and the field of view (280-300mm) was varied to maximize
in-plane resolution for each scan. The mean number of axial slices for the thigh was 30.27 (SD
1.53), and for the lower leg were 28.60 (SD 1.99).
63
Figure 1 Creating a 3 Dimensional model of the leg from an MRI scan using Mimics software
(Version 9.0, Materialise, Leuven) to determine muscle volume.
MR images were transferred to an independent workstation for digital reconstruction.
Isotropic voxel size was obtained using a trilinear interpolation routine. Muscles were manually
traced (see figure 1) and segmented for all subjects using a digitisation tablet (Intuos2, Wacom
Technology Corp., Vancouver, WA) and Mimics software (Version 9.0, Materialise, Leuven).
The segmented muscles included the semitendinosis, semimembranosis, biceps femoris,
rectus femoris, vastus lateralis and medialis, medial gastrocnemius, lateral gastrocnemius,
soleus, and the tibialis anterior. MV was calculated by summing the number of voxels
contained within each muscle and multiplying by the voxel dimension (1mm3). To account for
the large variation of age and height, and to account for confounding effects of skeletal
growth, MV was normalised to femur and tibia length as determined from MR images with
Mimics Software. MV was then presented as a percentage of MV (cm3) per femur (for thigh
(cm)) or tibial length (for shank (cm)).
We have previously reported the intraclass correlation coefficient (ICC) of MV using this
method23, reporting that both intra- and inter-rater reliability were high with ICC values
consistently greater than 0.92 and 0.94 (95% CI), respectively for quadriceps and hamstring
muscle volume23. In the present study, intra-rater reliability was high with an ICC value of 0.97,
tested in a random selection of five MRI scans of the hamstrings PRE and POST, whereby the
investigator was blinded to the scan time point and was. In this study, all data was processed
and analysed by one investigator (SW).
64
3.3.2.2 MUSCLE STRENGTH
A Biodex System-3 dynamometer (Biodex Medical Systems, Inc. Shirley, NY) was employed to
assess isometric strength of the knee flexors (KF) and knee extensors (KE). Children performed
three maximum isometric contractions of the KF and KE bilaterally, with the order of sidetested randomised. Trials evaluated muscle peak torque normalised to body weight (PT/BW) in
a static posture with the knee flexed at 90°. Standard straps constrained the upper body and
pelvis to avoid the contribution of other muscles in the assessment. The lower limb segment
was attached to the Biodex arm using the standard Velcro straps, leaving the ankle joint
unconstrained during the knee flexion/extension tasks. Continual verbal encouragement was
provided throughout the assessment with adequate rest and recovery in between contractions
to minimise muscle fatigue.
A hand held dynamometer (HHD) (Model 01163, Lafayette Instrument Company) was used to
determine maximal isometric strength for plantar flexion (PF) and Dorsi Flexion (DF) by a
trained and experienced physiotherapist. For PF, the child lay supine with straight legs, the
HHD was placed under the padding of the foot with the foot in as close to 90° as achievable.
The child was instructed to ‘point to toes down’, pushing against the HHD, whilst another
tester constrained the child at the knee and the hip. DF was measured with the child seated
upright, knee’s flexed at 90° and the HHD positioned on top of the foot. The child was
constrained at the knee, hips and torso, with arms crossed over the chest. For consistency of
results, the same assessor recorded all measurements for both assessment time points.
3.3.2.3 FUNCTIONAL ABILITY
The 6-minute walk test (6-MWT) was used to measure functional walking capacity27. In
addition to this children performed the Timed Up and Go (TUG) assessment from an
adjustable-height chair in accordance with the test protocol28.
3.3.3 STATISTICAL ANALYSIS
To estimate the effect of BoNT-A, we determined whether the difference in measures of
muscle volume and strength was significantly different from zero, accounting for possible
within-person correlations by using a mixed model with a random intercept. For functional
ability measures, a comparison of the pre and post BoNT-A group means were analysed using
repeated measures, two-tailed t-tests with a confidence interval of 95%,  level=.05. Effect
65
sizes were determined using Cohen’s d equation using the mean standard deviation of the two
scores beings compared. Each individual’s percentage change was grouped and averaged to
provide a mean percentage change for measures presented in the included tables. A post hoc
power analysis using the sample size of 15 revealed a power of 0.64.
3.4 RESULTS
3.4.1 SPASTICITY
All of the children in this study had a clinically appropriate response to BoNT-A treatment,
demonstrating improvements in spasticity. Total scores from the MAS were summated to
provide a representation of spasticity, with a lower score indicating less spasticity in the lower
limbs. Spasticity scores for the entire sample significantly decreased immediately following
BoNT-A injection, from a mean score of 10.07 (SD 3.94) to 8.27 (SD 2.12), (t(14)=2.358, p=.033,
ES=1.17).
3.4.2 PLANTAR/DORSI FLEXORS
This section on plantar/dorsi flexor muscle morphology and strength changes relates to all 15
children in the study as they all received BoNT-A to the gastrocnemius.
There were no significant changes in the MV for the total PF muscle group (the combination of
the soleus, and lateral and medial gastrocnemius) across the two time points (t(14)=-0.195,
p=0.848, ES=0.01). The combined volumes of the lateral and medial gastrocnemius showed a
significant decrease in gastrocnemius volume (t(14)=-2.42, p=.030, ES=0.17) of 4.47% (SD
8.57%), whilst the soleus volume had a significant increase of 3.96% (SD 8.05%), (t(14)=2.205,
p=.045, ES=0.10). The prime antagonist muscle of the DF group, the tibialis anterior, remained
constant with no significant change in MV (t(14)=0.645, p=.529, ES=0.05) (table 1).
There were no significant differences reflected in the measures of strength as measured by the
HHD for the plantar flexors or dorsi flexors (table 1).
66
Table 1 Muscle volumes and strength of the lower leg for 15 children (30 legs) receiving
BoNT-A to the gastrocnemius muscle group. All values for muscle volume (MV) are
expressed as % of muscle volume (cm3) divided by tibia length (cm). Strength values are in
kilograms. PRE and POST group averages and the average of each individuals percentage
change are presented. *significance at p<0.05
Pre
Post
Mean individual
% change
P value
ES
Gastrocnemius MV
3.00
SD 0.93
2.84
SD 0.85
-4.47
SD 8.57
p=.003*
ES=0.17
Soleus MV
4.32
SD 1.42
4.46
SD 1.38
3.96
SD 8.05
p=.045*
ES= 0.10
Total PF MV
7.32
SD 2.25
7.30
SD 2.12
0.45
SD 7.15
p=.848
ES= 0.01
Total DF MV
1.27
SD 0.34
1.29
SD 0.32
2.64
SD 12.02
p=.529
ES= 0.05
PF strength
29.80
SD 7.62
30.46
SD 8.71
2.45
(SD 17.92
p=.277
ES=0.24
DF strength
12.04
SD 4.73
12.23
SD 3.85
1.23
SD 20.97
p=.788
ES=0.25
3.4.3 KNEE FLEXORS/EXTENSORS
In reporting the measured morphological response of the hamstring (KF) and quadriceps (KE)
muscle, the results of the 10 children (20 legs) that received BoNT-A to the gastrocnemius are
reported separately from the five children (10 legs) who received medial hamstring injections
in addition to the gastrocnemius.
3.4.3.1.1 BONT-A TREATMENT IN THE GASTROCNEMIUS (N=10 CHILDREN, 20 LEGS)
There was a non-significant change of 2.85% (SD 6.17%) in the MV of the total hamstring
muscle group (t(9)=1.788, p=.107, ES=0.10) in the 10 children who received BoNT-A in the
gastrocnemius. When considering the individual muscles of the hamstring group, we found
that whilst the biceps femoris approached a significant increase by 4.67% (SD 8.54%), (t(9)=2.221, p=0.053, ES= 0.19), the MV of the medial hamstrings (semitendinosis and
semimembranosis) remained relatively constant (t(9)=0.535, p=.606, ES= 0.04).
The antagonist to the hamstring, the quadriceps muscle (KE) group increased its total MV
significantly by 4.23% (SD 5.84%), (t(9)=2.658, p=.026, ES=0.17).
67
3.4.3.1.2 BONT-A TREATMENT IN THE GASTROCNEMIUS AND MEDIAL HAMSTRINGS
(N=5 CHILDREN, 10 LEGS)
In the group of five children (10 legs) who had BoNT-A injections in both the gastrocnemius
muscle group and the medial hamstring there was no significant change in total hamstring (KF)
muscle volume (t(4)=-1.455, p=.219, ES=0.29). However the medial hamstrings did show a
decrease of 5.89% (SD 9.23%) in MV but was not statistically significant (t(4)=-2.007, p=.076,
ES=0.45). The prime antagonists, the quadriceps muscle group (KE) displayed no significant
change in morphology (t(9)=0.190, p=.859, ES=0.01) (table 2).
Table 2 PRE and POST group averages, with the grouped average of each individuals
percentage change in muscle volumes of the thigh for 10 children (20 legs) receiving BoNT-A
to the gastrocnemius muscle group and for 5 children (10 legs) receiving BoNT-A to the
medial hamstirngs and gastrocnemius. All values are expressed as % of muscle volume
(cm3) /femur length (cm). *significance at p<0.05
BoNT-a treatment Gastroc only
(N=10 children, 20 legs)
Muscle
group MV
Medial
Hamstring
Biceps
Femoris
Total
Hamstring
Total
Quadriceps
BoNT-A treatment Gastroc + Hamstring
(N=5 children,10 legs)
Pre
Post
Mean
individual
% change
P value
ES
Pre
Post
Mean
individual
% change
P value
ES
3.52
3.56
1.80
p=.606
2.87
2.68
-5.89
p=.076
SD 0.94
SD 0.84
SD 6.86
ES= 0.04
SD 0.47
SD 0.38
SD 9.23
ES=0.45
2.60
2.71
4.67
p=.053*
2.34
2.31
-1.14
p=.674
SD 0.56
SD 0.55
SD 8.54
ES= 0.19
SD 0.39
SD 0.40
SD 8.34
ES=0.08
6.12
6.26
2.85
p=.107
5.21
4.99
-3.84
p=.219
SD 1.43
SD1.34
SD 6.17
ES= 0.10
SD 0.82
SD 0.74
SD 8.07
ES=0.29
12.51
12.96
4.23
p=.026*
12.41
12.44
-0.14
p=.859
SD 2.79
SD 2.57
SD 5.84
ES= 0.17
SD 2.21
SD 2.49
SD 2.71
ES= 0.01
3.4.3.2 MUSCLE STRENGTH AND FUNCTION
3.4.3.2.1 BONT-A TREATMENT IN THE GASTROCNEMIUS (N=10 CHILDREN, 20 LEGS)
From the 10 children (20 legs) receiving BoNT-A injections in the gastrocnemius muscles only,
there was no statistical change in the KF muscles (-2.19% SD 42.34%, t(9)=-1.155, p=.277,
ES=0.26), or the the KE muscles (11.70%, SD 33.72%, t(9)=0.389, p=.706, ES=0.05) (table 3).
68
In the 10 children having BoNT-A to the gastrocnemius muscles only, there were no statistically
significant changes after BoNT-A in function as assessed by the TUG, completing the task in
4.50 sec (SD 0.95) before BoNT-A compared with 4.66 sec (SD 0.98) after BoNT-A, a 3.94%
increase in time (SD 12.54%),(t(9)=-0.925, p=.379, ES=0.16). There was also no statistically
significant change in the distance covered in the 6-MWT; 577.49m (SD 73.53) to 559.89m (SD
72.14), a 2.89% decrease in distance (SD 6.45%),(t(9)=1.442, p=.183, ES=0.24).
3.4.3.2.2 BONT-A TREATMENT IN THE GASTROCNEMIUS AND MEDIAL HAMSTRINGS
(N=5 CHILDREN, 10 LEGS)
In the measures of muscle strength, isometric peak torque showed no statistically significant
change in the KF (t(4)=-1.088, p=.338, ES=0.57) or KE muscles (t(4)=-0.453, p=.674, ES=0.38)
(table 3).
In the five children who had gastrocnemius and hamstring injected, there were no statistically
significant changes in the TUG after BoNT-A, completing the task in 4.76 sec (SD 0.91) before
and 4.68 sec (SD 0.91) after BoNT-A, a 0.89% decrease in time (SD 11.79%), (t(4)=0.356,
p=.740, ES=0.09). Distance covered in the 6-MWT also did not statistically change after BoNTA, from 512.82 m (SD 103.65) to 517.55m (SD 99.77), A 1.34% increase (SD 8.78%) (t(4)=-0.234,
p=.826, ES=0.05).
Table 3 PRE and POST average values of knee flexor and knee extensor strength (Isometric
peak torque), with the grouped average of individual percentage changes in 10 children (20
legs) receiving BoNT-A to the gastrocnemius muscle group, and 5 children (10 legs) receiving
BoNT-A to the medial hamstrings and gastrocnemius. Values are normalised to body
weight.*significance at p<0.05
Gastroc
n=10 children (20 legs)
Isometric
Pk Torque
(Nm/Kg)
Pre
Knee
Flexion
Knee
Extension
Gastroc & HS
n=5 children (10 legs)
Post
Mean
individual
% change
P value
ES
Post
Mean
individual
% change
Pre
P value
ES
83.86
SD 47.79
72.36
SD 40.20
-2.19
SD 42.34
p=.277
ES=0.26
62.68
SD 7.94
56.09
SD 15.12
-9.75
SD 25.46
p=.338
ES= 0.57
205.86
SD112.74
211.85
SD108.44
11.70
SD 33.72
p=.706
ES= 0.05
207.10
SD 35.13
222.24
SD 44.17
8.70
SD 18.27
p=.674
ES= 0.38
69
3.5 DISCUSSION
This study has for the first time provided an in depth investigation into the immediate
morphological responses to BoNT-A injections of muscles of the lower limbs of children with
CP. In agreement with Schroeder et al’s., (2009)15 research on BoNT-A in the healthy muscle,
reports from the cosmetic industry17-19, and animal research13, 20, we also found evidence of
muscular atrophy in BoNT-A injected muscles. An average reduction of 4.5% was measured in
the gastrocnemius muscle of 15 children undergoing BoNT-A for spasticity management, whilst
five of those children who also had the medial hamstrings injected had an average decrease of
5.9% in the medial hamstring MV. These results are reassuring, in that whilst we did measure
atrophy, they appear to be much smaller than the concerning reports of almost 20% reduction
as seen in healthy adult muscles of the gastrocnmeius15, the 22-25% reduction in masseter
muscle thickness17, 18, and the changes seen in animal research of 32-50% decreases13,20. These
responses however should be viewed with perspective and compared with caution. Previous
reports of muscle atrophy use a variety of methods to measure muscle morphology, making it
difficult to draw true comparisons of results. In addition to this, the research in healthy
muscles reports the response of muscles to the first series BoNT-A injection. In our study in
pathological muscles, children had already received a minimum of 2 series of BoNT-A; the
responses reported here are likely to not be as strong as they may have been if it were to their
first injection of BoNT-A. Fortuna et al.,(2011)13 animal study on repeat injections of BoNT-A
reported that the greatest amount of atrophy occurred as the muscles first response to BoNTA. The animal studies have also indicated that muscle atrophy was not homogenous within a
muscle group exposed to BoNT-A, and could be affected by the muscle fibre type13, a factor
that could be highly variant in individuals with spastic muscle. The reality is that muscles in
children with CP are variable, and the use of BoNT-A for spasticity management is repeated
over many years. This study provides the first snapshot into morphology alterations of this
population. From here research needs to look at alterations after the muscles first BoNT-A
injection, and delve further into the muscles response following sequential series’ of BoNT-A.
In exploring the alterations of each of the injected, synergist and antagonist muscle to BoNT-A,
an interesting outcome emerged. Whilst the volume of the injected gastrocnemius muscle
decreased by 4.5%, the soleus muscle matched the decrease with nearly a 4% increase in
volume, with a consequential total volume for the PF muscle group that is relatively stable
after the BoNT-A. This is a potential indication of a compensatory reaction with synergist
hypertrophy. The prime antagonist muscle, the tibialis anterior, also did not show any changes
70
in MV, whilst increases were also measured in the hamstring and quadriceps MV (out of the
ten children not receiving BoNT-A in the hamstrings).
The quadriceps MV increase was complimented with an 11.7% increase in KE strength, in
accordance with evidence that muscle size is related to muscle strength21, 22. The KF strength
however, indicated more of a decreasing trend, possibly in part a result of the contribution of
the gastrocnemius in knee flexion, weakened as a response to BoNT-A. However with no
statistical significance, and small effect sizes, we cannot extrapolate our observations of
strength but merely speculate. The HHD measures strength for the PF and DF also showed no
significant changes, and large variations in scores. Indeed a slight increase in isometric strength
was measured in the PF and DF following the BoNT-A, possibly attributed to the participants
ease in achieving range following the BoNT-A treatment. Unfortunately, our measures of
strength are limiting in that they cannot separate out the individual contributions of each
muscle, but instead provide us with a more holistic assessment of the torque about a joint.
It was a slightly different story for the five children who had BoNT-A injected to both the
medial hamstring and gastrocnemius. As previously mentioned, there was a decreasing trend
in medial hamstring volume that approached significance; the synergist biceps femoris muscle
did not increase in response, but rather showed a small decrease in MV. This resulted in an
overall decrease of 3.8% for the total hamstring group MV that corresponded with a decrease
in KF strength, that although, was not statistically significant, had a moderate effect size of
0.57. The antagonist quadriceps MV showed no notable change, whilst the strength of the KE
showed an increasing trend but also did not reach statistical significance. Whilst these minor
alterations may be explained by the muscle strength–size relationship21, 22, we cannot rule out
the possibility of any neurological alterations as a result of BoNT-A altering innervation
patterns.
A possible confounding limitation in our study was that four other muscles in the leg in
addition to the gastrocnemius or hamstrings were targeted for injection for five of the children
included in this study which may have compromised results. This was determined by clinical
decision and was out of the researcher’s control. However, doses were minimal and only two
children received injections into an additional muscle in the gastrocnemius and hamstring
injected group. The soleus muscle, as well as the gastrocnemius muscle, was injected in two of
the children in this study; when we removed their results the increase of the soleus muscle
71
was even greater at 4.4% (with the gastrocnemius MV decrease changing to 5.4%), which
supports our premise of synergist hypertrophy of the soleus. Instituting MRI analysis in
research designs is costly and time consuming; unfortunately the addition of a control group
(no treatment or saline injected) was not feasible for this study. Our measurements of change
could be queried as many of our statistics include small effect sizes, for example the
gastrocnemius decrease in MV was significant but had a small effect size, whilst the drop in the
injected hamstring muscle approached significance yet had a moderate effect size. In addition
to this, interpretations of our results are limited by our small sample size. With this in mind, it
is important that findings within this study be viewed with some caution. Nonetheless, we
believe the new information presented in this study to be clinically important.
The morphological alterations in spastic muscle in our sample of children with CP did not show
atrophy as severe as that shown in animal studies and healthy muscle13. This is certainly
optimistic for the continued future of BoNT-A use, however as mentioned, the initial response
to BoNT-A in spastic muscle may be different. Despite this, this study also appeared to uncover
the possibility of compensatory hypertrophy in synergist muscles as a response to atrophy of
the injected muscles. With this in mind for the future application of BoNT-A, the morphological
response of muscle to BoNT-a treatment may not be limited to the injected muscle alone. The
hypertrophy is likely a product of an increased physiological demand on the synergist muscle,
the increasing work and load of the synergist muscle, leading to work-induced hypertrophy29.
In terms of muscle strength, our results showed no significant changes from BoNT-A but may
indicate potential changes, in particular in children who are having multiple muscles injected.
It is also important to note that the morphological alterations following BoNT-A did not have
any significant detrimental effects on the children’s functional performance. In the present
study the effects of BoNT-A injections where measured to correspond with the BoNT-A taking
peak effect; to get a deeper understanding, follow up assessments would provide us with a
clearer picture as to how the muscles are responding to the BoNT-A in the longer term.
3.6 CLINICAL IMPLICATIONS
This is the first study, to our knowledge, to report upon the immediate morphological
alterations in spastic muscles following BoNT-A treatment. It has demonstrated reductions in
muscle volume in the injected muscle, and hypertrophy in a synergist muscle as a
compensatory reaction in children with CP. This potentially has a role in explaining the good
clinical and functional response in children after BoNT-A injections. The atrophy measured in
72
our sample of children with CP was not as large as that reported in animal and healthy muscle
research. Whilst strength deficits were not seen following a single site injection in this study,
attention should be paid to muscle alterations of children undergoing treatment to multiple
sites on repeated occasions.
3.7 ACKNOWLEDGEMENTS
This project was supported by the Princess Margaret Hospital (PMH) Foundation Grant as well
as by the University of Western Australia’s Research and Development Awards. The authors
would like to thank the Department of Paediatric Rehabilitation, PMH for their support and
assistance with recruitment, the Department of Diagnostic Imaging, PMH for their assistance
and knowledge in data collection and the contribution of the School of Sport Science, Exercise
& Health at UWA for the use of equipment and facilities. They would also like to thank Tania
Shillington, Bree Dwyer and Martin Spits for their role with the data collection, and Associate
Professor Eve Blair (Telethon Institute for child health research) for her statistical advice in the
preparation of this manuscript.
73
3.8 REFERENCES
1.
Heinen F, Molenaers G, Fairhurst C, et al. European consensus table 2006 on
botulinum toxin for children with cerebral palsy. Eur J Paediatr Neurol. 2006;10:215-25.
2.
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9.
Graham HK. Botulinum toxin type A management of spasticity in the context of
orthopaedic surgery for children with spastic cerebral palsy. Eur J Neurol. 2001;8:30-9.
10.
11.
Mohamed KA, Moore AP, Rosenbaum L. Adverse events following repeated injections
with botulinum toxin A in children with spasticity. Dev Med Child Neurol. 2001;43:791-2.
12.
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2011;44:39-44.
14.
15.
16.
Dunne J, Singer BJ, Silbert PL, Singer KP. Prolonged vastus lateralis denervation after
botulinum toxin type A injection. Mov Disord. 2010;25:397-401.
17.
Kim J, Shin J, Kim S, Kim C. Effects of two different units of Botulinum Toxin Type A
evaluated by computed tomography and electromyographic measurements of human
masseter muscle. Plast Reconstr Surg. 2007;119:711-7.
18.
Kim N, Chung J, Park R, Park J. The use of Botulinum Toxin Type A in aesthetic
mandibular contouring. Plast Reconstr Surg. 2005;115:919-30.
19.
Han KH, Joo YH, Moon SE, Kim KH. Botulinum toxin A treatment for contouring of the
lower leg. J Dermatolog Treat. 2006;17:250-4.
20.
21.
Muscle Nerve. 2000;23:1647-66.
22.
Kinetics; 2002.
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alterations over six months of growth. Muscle Nerve. 2012;46:360-6.
24.
25.
Child Neurol. 2011;53:543-8.
26.
Bohannon R, Smith M. Interrater reliability of a modified Ashworth scale of muscle
spasticity. Phys Ther. 1987;67:206-7.
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27.
28.
Williams E, Carroll S, Reddihough D, Phillips B, Galea M. Investigation of the Timed ‘Up
& Go’ Test in children. Dev Med Child Neurol. 2005;47:518-24.
29.
Goldberg
AL.
Work-induced
growth
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skeletal
muscle
of
normal
and
hypophysectomized rats. Am J Physiol. 1967;213:1193-8.
76
CHAPTER FOUR
INTERVENTION IN CHILDREN WITH CEREBRAL PALSY: THE IMPACT ON
MUSCLE MORPHOLOGY AND STRENGTH
This manuscript was accepted for publication into Disability and Rehabilitation in July 2012.
Williams SA, Elliott CM, Valentine J, Gubbay A, Shipman P, Reid SL. Combining Strength
Training and Botulinum Neurotoxin intervention in children with Cerebral Palsy: The impact on
Muscle Morphology and Strength. Disabil Rehabi. 2012 (Accepted for publication)
The PhD candidate, Sîan A Williams, accounted for 80% of the intellectual property associated
77
FOREWORD
The first paper confirmed the presence of localised muscle atrophy following BoNT-A to the
gastrocnemius and medial hamstring muscles, but this did not significantly influence the force
output of the muscle groups. Children with CP are known to have smaller and weaker muscles
then their typically developing peers. This paper investigates the effect of a home based
strength training, added in combination with BoNT-A injections to simultaneously target
muscle weakness and spasticity. Specifically, it demonstrates the outcomes of muscle strength,
morphology and functional goal attainment. It also questions the most effective timing of the
strength training in relation to the BoNT-A, to guide clinicians in the application of this
treatment concept.
78
4.1 ABSTRACT
Purpose: Investigate the combination effects of strength training and Botulinum Toxin Type-A
(BoNT-A) on muscle strength and morphology in children with Cerebral Palsy (CP).
Methods: Fifteen children receiving BoNT-A, classified as Spastic Diplegic CP, GMFCS I-II, and
aged 5-12years were recruited for this study. Randomly allocated to 10 weeks of strength
training either before or after BoNT-A, children were assessed over 6 months. Eight of the 15
children also completed a control period. The Modified Ashworth Scale measured spasticity.
The Goal Attainment Scale (GAS) assessed achievement of functional goals. Magnetic
Resonance Imaging assessed muscle volume (MV). Instrumented dynamometry assessed
strength.
Results: Spasticity was significantly reduced following BoNT-A injection (p=.033). Children
made significant isokinetic strength gains (mean p=.022, ES=0.57) in the intervention period
compared to the control period (mean p=.15, ES=0.56). Irrespective of timing, significant
strength improvements were seen immediately (10 weeks) and over 6 months for all children.
This was also the case for improvements in the GAS (immediately: mean p=.007, ES=4.17,
6months: mean p=.029, ES=0.99), and improvements in MV in all assessed muscles.
Conclusion: The simultaneous use of BoNT-A and strength training was successful in spasticity
reduction, improving strength and achieving functional goals, over and above treatment with
BoNT-A alone. Muscles targeted for BoNT-A injection should be included in strength training.
79
4.2 INTRODUCTION
Children with Cerebral Palsy (CP), have been shown to have significantly weaker muscles than
their typically developing peers3,
4
which can contribute to significant motor impairment5.
Muscle weakness is linked with limitations in functional activities and can make activities of
daily living such as walking5,6 difficult to accomplish. The cause of muscle weakness in CP may
be attributed to a combination of abnormal muscle structure and/or altered neural
mechanisms6.
The morphological and structural properties of a muscle influence its ability to generate force7
such that a decrease in muscle volume can reasonably be associated with a diminished ability
of the muscle to produce torque and power8. A recent review in spastic CP found consistent
evidence for reduced muscle size in the lower limb8. The affected muscles of children with CP
display reduced muscle volume, cross-sectional area, thickness and muscle belly length
compared to their non-paretic limb and the muscles of typically developing children8. In
addition to these anatomical factors, individuals with CP have greater amounts of cocontraction9 and are less able to activate their muscles maximially10. Spasticity is a very
common clinical sign in children with CP and is considered the main cause of the secondary
musculoskeletal complications that arise11. Spasticity is associated with abnormalities in
muscle tone, overactive stretch reflexes and movement and/or postural control responses,
and has been suggested to contribute both to the impairment of function and reduced
longitudinal muscle growth in children with CP12. With both muscular weakness and spasticity
considered to be significantly detrimental to function in children with CP5 there is a call for
research to determine the efficacy of treatment for these motor impairments.
Strength training is now recognised as an effective intervention for improving muscular
strength in children with CP13. A growing number of studies confirm that following strength
training, people with CP can achieve significant strength improvements that are translatable to
gains in motor function13-15. Contrary to this evidence and to previous systematic reviews6, 13, 1617
, one systematic review18 suggested strength training to be neither effective nor worthwhile
in children and adolescents with the CP, however this review evaluated only (six) randomized
controlled trials, and did not suggest strength training to be harmful or that it should no longer
be administered in clinical practice for children with CP. The outcomes of this review have
been questioned, Verschuren and Colleagues (2011)17 reasoned that the conclusions of Scianni
be viewed with caution given that the training protocols of the included papers were
80
inconsistent with guidelines set for resistance training in children. Despite this particular
review, strength gains have been associated with improvements relating to walking13-15,
flexibility, posture and balance19. McNee and Colleagues (2009)20 have also reported that
alongside improvements in strength, muscles also increase in volume after 5 and 10 weeks of
strength training in children with CP. McNee’s research indicates that strength training could
amend the pre-existing muscle size and muscle strength deficit that is common with CP20.
Whilst strength training targets muscular weakness, Botulinum Toxin Type-A (BoNT-A) is an
established treatment option for spasticity management for children with CP21.
The benefits of BoNT-A treatment include a reduction in muscle tone22, increased joint range
of motion22, improved gait patterns22, and functional improvements23. However, there is a
known association between the use of BoNT-A and muscle weakness, with reports of
generalised muscle weakness24 and weakness in neighbouring non-targeted muscles24,
25
.
Recent publications have also raised concern regarding the effect of BoNT-A on muscle size
and morphology26, 27. Schroeder and Colleagues (2009)27 identified neurogenic atrophy up to 12
months following BoNT-A in healthy adults. Knowing that muscle structure and size is
associated with muscle strength5, muscle atrophy could therefore affect its ability to generate
force. In children with CP who have pre-existing weakness, added weakening could be
particularly detrimental.
With strong supportive evidence for the use of strength training to target muscular weakness,
and similarly, the use of BoNT-A for spasticity management and improved function, should we
be applying strength training concurrently with BoNT-A treatment to further improve clinical
outcome for patients? We hypothesize that with the combination of both BoNT-A and strength
training, children with CP can have improvements in muscle size and muscle strength
simultaneous with a reduction in spasticity. Furthermore we aim to determine when strength
training should occur in relation to BoNT-A treatment to optimise functional outcomes for the
patients.
4.3 METHODS
4.3.1 PARTICIPANTS
Ten boys and five girls with spastic diplegia, classified as Gross Motor Function Classification
System (GMFCS) level I-II were recruited from the Cerebral Palsy Mobility Service at Princess
Margaret Hospital (PMH) in Perth, Australia. The fifteen participating children had a mean age
81
of 8years 5mo (SD 1yr 10 mo, range 5-11yrs), an average height of 129.87cm (SD 10.92cm)
average weight of 27.97kg (SD 7.43kg) and Body Mass Index of 16.34 (SD 2.4). No child had
undergone serial casting in the previous six months and no child had a history of lower limb
surgery. Ethical approval for the study was obtained from the Ethics Committee of PMH
(1766/EP), and from the University of Western Australia. Written consent was obtained from
the parents of all the participants.
All 15 children were receiving BoNT-A treatment for spasticity management bilaterally in their
lower limbs, and had already received a minimum of two series of BoNT-A prior to the
injection series included in the study (maximum series=15, mean series=8.93). The muscle(s)
selected for injection were determined by the child’s physician based on clinical assessment
and functional goal setting, the total dose of BoNT-A (Botox®, Allergan, Irvine, CA, USA) was
empirically selected for each muscle. All participants received BoNT-A to bilateral medial
gastrocnemius' (30 legs injected; 2-6U/kg), and five participants also received BoNT-A to
bilateral medial hamstrings (10 legs; 2-4U/kg). Other muscles injected included the soleus
(4legs; 1-2U/kg) adductors (2 legs; 1U/Kg), rectus femoris (2 legs; 1U/Kg), and tibialis posterior
(1 leg; 1U/Kg). No child had more than three muscles injected per leg.
4.3.2 DESIGN AND PROCEDURES
The study design, dictated by current clinical care, utilised a repeated measures crosscomparison design with a 6month pre-intervention baseline phase serving as a control period
(Figure 1). Children in the study were block randomised by age, gender and GMFCS level into
either a PRE or POST BoNT-A strength training group. Children completed four assessments;
Assessment 1 (A1) timed approximately 12 weeks prior to their scheduled BoNT-A, Assessment
2 (A2) approximately 2 weeks prior to their scheduled BoNT-A, Assessment 3 (A3) on average 5
weeks (SD 1week, range 3-6weeks) post injection and Assessment 4 (A4) approximately 14
weeks post injection. The PRE group completed strength training in the weeks between A1-A2
and the POST group completed the training between A3-A4. In the weeks where the children
were not allocated strength training, they continued with their normal care routine, which
included their standard clinical care. Eight children completed assessments at the same time
points as A1 and A4 scheduled around their BoNT-A for a control period assessment.
82
BoNT-A
Normal Care
Routine
BoNT-A
A2 A3
A1
B
Normal Care
Routine
PRE strength
training
Normal Care
Routine
Normal Care
Routine
POST strength
training
Control Period n=8
W-26
W-12
A4
W0
Intervention period n=15
W12
W26
Figure 1 Cross-comparison study design, with a pre-intervention baseline assessment for
eight participants forming a control (Week-26 to Week0) and intervention (Week0 to Week
26) period. The dashed lines represent BoNT-A injection. In the intervention, children were
allocated to either PRE or POST BoNT-A strength training.
4.3.2.1 ASSESSMENTS
All assessments were conducted by the same assessor who was blinded to group allocation.
4.3.2.1.1 GOALS
For each child, individual goals were defined and translated into assessable tests so that
quantitative scores could be obtained. To assess each child’s outcome over the research time
points, scores were input and rated into the Goal Attainment Scale (GAS) by an independent
Occupational Therapist who was blinded to group allocation. The GAS is an individualised
criterion referenced measure that can be used to assess qualitative changes and small but
clinically significant improvements in motor development and function over time28. The scores
of all individual goals were summed and converted into a standard T-score with an equal
weight for each goal28. Converted GAS scores of 50 or more are representative of a successful
treatment outcome.
4.3.2.1.2 SPASTICITY AND SELECTIVE MOTOR CONTROL
Spasticity was assessed in each leg using the Modified Ashworth Scale (MAS)29. The Selective
Control Assessment of the Lower Extremity (SCALE) was used to measure selective voluntary
motor control30. Both measures were undertaken by an experienced Physiotherapist in
accordance with the recommended methodologies.
4.3.2.1.3 MUSCLE STRENGTH
A Biodex System-3 dynamometer (Biodex Medical Systems, Inc. Shirley, NY) was employed to
assess isometric and isokinetic strength of the knee flexors (KF) and knee extensors (KE).
Children performed three maximum isometric contractions, and three continuous maximum
isokinetic repetitions, of the KF and KE bilaterally. The order of action type and side-tested was
randomised. Isometric trials evaluated muscle peak torque normalised to body weight (PT/BW)
83
in a static posture with the knee flexed at 90°. Isokinetic trials assessed muscle peak torque
(PT/BW) and joint power throughout range of motion at 60°/s. Continual verbal
encouragement was provided throughout the assessment with adequate rest and recovery in
between contractions to minimise fatigue. The peak torque is the maximum force that a
muscle group can produce (either isometrically or isokinetically); whilst the joint power gives
us an indication of how fast the muscle can develop force. A hand held dynamometer (HHD)
(Model 01163, Lafayette Instrument Company) was used to determine maximal isometric
strength of the gastrocnemius and tibialis anterior in standardised positions by a trained
physiotherapist and provided a peak score in kilograms. For consistency of results, the same
assessor completed all measurements for all assessment time points.
4.3.2.1.4 MUSCLE MORPHOLOGY
Muscle volumes (MV) of the lower limbs were assessed using Magnetic Resonance Imaging
(MRI). Scans were performed in the morning after a nights rest to standardise against factors
such as exercise. Axial spin-echo T1-weighted MR images were acquired bilaterally from the
level of the ankle malleoli to the iliac crest while subjects lay prone in a 1.5T whole body MR
unit (Magnetom Sonata Maestro Class, Siemens Medical Solutions, Erlangen, Germany).
Subjects were positioned in neutral hip rotation, maintained passively using standard patient
positioning with foam pads. Images of the thigh and lower leg were collected using a repetition
time of 572ms, echo time of 13ms, slice thickness of 5mm, and mean inter-slice gap between
5-7mm. A matrix size of 256×160mm was used for all thigh scans, and 256x144mm for lower
leg, and the field of view (280-300mm) was varied to maximize in-plane resolution for each
scan. The mean number of axial slices for the thigh was 30.27 (SD 1.53), and for the lower leg
were 28.60 (SD 1.99). MR images were transferred to an independent workstation for digital
reconstruction. Isotropic voxel size was obtained using a trilinear interpolation routine.
Muscles were manually traced and segmented for all subjects using a digitisation tablet
(Intuos2, Wacom Technology Corp., Vancouver, WA) and Mimics software (Version 9.0,
Materialise, Leuven). The segmented muscles summed to produce hamstring (HS) values;
semitendinosis, semimembranosis, and the biceps femoris, to produce quadriceps (Quads)
values; rectus femoris, vastus lateralis and medialis, to produce plantar flexor (PF) values;
medial and lateral gastrocnemius, and soleus, and dorsi flexor (DF) values; the tibialis anterior.
Muscle volume was calculated by summing the number of voxels contained within each
muscle and multiplying by the voxel dimension (1mm3). MV was normalized to femur length
84
for the HS and Quads, and tibia length for the PF and DF, as measured from MR images with
Mimics Software, and presented as a percentage of MV (cm3) divided by bone length (cm).
In previous research by the same authors of this study a two-way random effects intraclass
correlation coefficient (ICC) was performed to quantify intra-and inter-rater reliability between
two independent raters using this method of assessing morphology, and found that both intraand inter-rater reliability were high with ICC values consistently greater than 0.92 and 0.94
(95% CI), respectively for quadriceps an hamstring muscle volume31.
4.3.2.2 TRAINING PROGRAM
Participants completed a home based strength training program, training three times a week
for 10 weeks. Program coordination and progression was conducted fortnightly by a visiting
exercise physiologist, with the remaining training sessions conducted by a trained family
member. Each training session included manual and passive stretching of the lower limb
muscle groups. The design of the strength program was based on the child’s initial strength
assessment and their functional goals. Other muscle groups, aside from those reported in this
paper, were also included in the strength programs. Strengthening exercises were progressive
with repetitions and loading levels increasing as the child’s strength increased in accordance
with the American College of Sports Medicine guidelines32. The exercises were performed in
three sets bilaterally, with adequate rest between sets. The program initially focused on motor
control; with manual resistance and the use of a Thera-band(s), and the establishment of base
strength with ankle weights, increasing in number of repetitions and then loads. Over the 10
weeks of the training, the program progressed to more complex movements and functional
tasks reflecting the child’s goals. Equipment was provided throughout the program, including
ankle weights, thera-bands, Fit balls, and Duradiscs. Participants were requested not to take up
any new activities and remain constant with regard to their usual therapy program, which was
recorded, over the course of the study.
A two-tailed paired t-test was performed using mean scores of the eight children assessed in a
control period and in the intervention period, with another paired t-test to determine if the
change was significantly different between groups. Six months separated each assessment,
with BoNT-A at 3months midway between each assessment.
85
In the intervention period, to determine changes in measures over strength training and
normal care routine periods, a series of two-tailed paired t-Tests were performed for each
pair-wise comparison over the investigated time points (i.e. PRE group measures at A1 paired
with PRE group measures at A2). To determine if there was a differential effect of timing of
strength training in relation to BoNT-A to the overall outcome, a mixed model linear ANOVA
was performed, where the ‘group’ allocation was entered as a fixed effect. All of the above
statistics were tested with a confidence interval of 95%,  level=.05. Effect sizes were
determined using Cohen’s d equation using the mean standard deviation of the two scores
beings compared.
4.4 RESULTS
4.4.1 BONT-A COMPARED WITH BONT-A AND STRENGTH TRAINING
Eight children, mean age 8yrs 3mo (SD 2yrs), (n=6 GMFCS I, n=2 GMFCS II), took part in a
control phase prior to continuing onto the intervention phase. Muscle strength and
morphology results are presented for the control and intervention phase below (Table 1).
4.4.1.1.1 KNEE FLEXOR STRENGTH
KF strength significantly increased in the intervention group in isometric PT/BW (p=.012,
ES=0.53), isokinetic PT/BW (p=.047, ES=0.43), and muscle power (p=.008, ES=0.59). KF strength
in the control group did not change significantly, however again the changes made over the
control and intervention period did not differ significantly (p>.05) (Table 1).
4.4.1.1.2 KNEE EXTENSOR STRENGTH
In the intervention group strength training was shown to increase KE strength as represented
by significant increases in isometric PT/BW (p=.003, ES=0.66), Isokinetic PT/BW significantly
(p=.002, ES=0.73) and muscle power (p=.031, ES=0.52). Comparatively, the control group
significantly increased only in the measure of muscle power (p=.033, ES=0.75). Changes made
over the control and intervention period did not differ significantly (p>.05) (Table 1).
86
4.4.1.1.3 ISOMETRIC ASSESSMENT OF MUSCLES
Gastrocnemius (p=.046, ES=0.46) and tibialis anterior (p<.001, ES=0.61) strength showed
significant increases following the strength training intervention period. However, the control
group also had significant increases in gastrocnemius (p<.001, ES=1.29) and tibialis anterior
(p=.012, ES=0.88) strength. There was a significant difference in change between groups for
the gastrocnemius (p=.030, ES=1.09), though not in the tibialis anterior (Table 1).
Table 1 Mean change in strength and muscle volume scores for eight children over a 6month
control period of BoNT-A, and over a 6month intervention period of strength training and
BoNT-A. ES=effect size, SD=standard deviation. *Denotes significance, p<.05, #Denotes
approaching significance, p<.06.
Control
T value,
P Value, ES
Strength
training
T value,
P Value, ES
Between groups
T value, P Value, ES
Knee Flexor Strength
Isometric Pk Torque
(Nm/kg)
18.60
SD 35.28
t=-2.110, p=.052,
#
ES=0.46
28.52
SD 39.68
t=-2.874, p=.012,
ES=0.53*
t=-0.660, p=.518,
ES=0.26
Isokinetic Pk Torque
60°/s (Nm/kg)
15.93
SD 34.10
t=-1.868, p=.081,
ES=0.55
16.56
SD 30.71
t=-2.168, p=.047,
ES=0.45*
t=-0.037, p=.963,
ES=0.02
Isokinetic Power
60°/s (Watts)
3.09
SD 6.64
t=-1.859, p=.083,
ES=0.61
4.04
SD 5.26
t=-3.074, p=.008,
ES=0.59*
t=-0.334, p=.742
ES=0.16
Knee Extensor Strength
Isometric Pk Torque
(Nm/kg)
4.20
SD 40.37
t=-0.219, p=.829,
ES=0.05
68.19
SD 76.75
t=-3.554, p=.003,
ES=0.66*
t=-2.09, p=.054,
#
ES=0.83
Isokinetic Pk Torque
60°/s (Nm/kg)
20.27
SD 37.25
t=-1.144, p=.271,
ES=0.35
51.75
SD 54.87
t=-3.773, p=.002,
ES=0.73*
t=-1.125, p=.278,
ES=0.50
Isokinetic Power
60°/s (Watts)
6.63
SD 11.33
t=-2.343, p=.033,
ES=0.75*
5.31
SD 8.91
t=-2.386, p=.031,
ES=0.52*
t=0.278, p=.784,
ES=0.13
Isometric Muscle strength
Gastrocnemius
(kg)
9.53
SD 6.07
t=-6.281, p<.001,
ES=1.29*
3.13
SD 5.74
t=-2.179, p=.046,
ES=0.46*
t=2.396, p=.030,
ES=1.09*
Tibialis Anterior
(kg)
3.33
SD 4.69
t=-2.839, p=.012,
ES=0.88*
1.71
SD 1.28
t=-5.356, p<.001,
ES=0.61*
t=1.276, p=.221,
ES=0.54
Muscle Volume
HS Volume
3
(cm /cm)
0.82
SD 0.58
t=-5.673, p<.001,
ES=0.60*
0.47
SD 0.44
t=-4.295, p=.001,
ES=0.32*
t=1.580, p=.135,
ES=0.69
Quad Volume
3
(cm /cm)
0.68
SD 1.00
t=-2.718, p=.016,
ES=0.23*
1.52
SD 0.88
t=-6.870, p<.001,
ES=0.53*
t=2.051, p=.058,
ES=0.88
PF Volume
3
(cm /cm)
1.04
SD 0.81
t=-5.139, p=.001,
ES=0.60*
0.75
SD 0.65
t=-4.660, p<.001,
ES=0.40*
t=0.952, p=.354,
ES=0.39
DF Volume
3
(cm /cm)
0.08
SD 0.19
t=-1.763, p=.098,
ES=0.29
0.25
SD 0.14
t=-6.875, p<.001,
ES=0.80*
t=-0.831, p=.417,
ES=1.00
87
4.4.1.2 MUSCLE VOLUME
HS volume increased significantly over the control period (p<.001, ES=0.60) and the strength
training intervention period (p=.001, ES=0.32). Correspondingly the Quads also showed a
significant increase over the control period (p=.016, ES=0.23) and the strength training period
(p<.001, ES=0.53). MV for the PF had significant increases at both the control (p=.001, ES=0.60)
and the strength training time period (p<.001, ES=0.40), whilst the MV for the DF increased
significantly only over the strength intervention period (p<.001, ES=0.80). Changes made in MV
over the control and intervention period did not differ significantly (Table 1).
4.4.2 TIMING OF STRENGTH TRAINING
Fifteen children participated in the intervention phase of this study. Seven children, with a
mean age of 8yrs 2mo (SD 1yr 9mo, three males, four females) were allocated into the PRE
group training prior to receiving BoNT-A treatment, with eight children, mean age 8yrs 3mo
(SD 2mo, five males, three females) in the POST group, training following receipt of BoNT-A
treatment.
4.4.2.1 GOALS
Following the strength training period, the mean GAS converted T-score for the PRE group
significantly increased from 24.09 (SD 1.37) up to 66.74 (SD 11.24), (t(6)=-10.457, p<.001,
ES=6.76). For the POST group the T-score increased from 29.93 (SD 11.59) to 52.68 (SD 17.26),
(t(7)=-3.329, p=.013, ES=1.58). Between A1 and A4, with both groups undergoing strength
training and BoNT-A treatment, the PRE group increased its T score by 23.69 (t(5)=-2.747,
p=.040, ES=0.41), whilst the POST group increased by 28.67 (t(5)=3.490, p=.017, ES=1.58).
4.4.2.2 SPASTICITY
Total scores from the MAS were summated to provide a representation of spasticity, with a
lower score indicating less spasticity in the lower limbs. There was no significant change in
spasticity over the course of the strength training for either group (p>.05). Each individual
decreased their spasticity score, with a significant decrease in the entire sample of children’s
measures of spasticity immediately following BoNT-A injection (t(15)=2.358, p=.033, ES=1.17).
88
4.4.2.3 MOTOR CONTROL
Total SCALE scores were summated for each assessment and averaged for both legs, with a
maximum achievable score of 10. The PRE group went from a mean SCALE of 8.14 (SD 1.49) up
to 8.21 (1.47) after strength training, whilst the POST group went from a mean SCALE of 9.43
(SD 0.79) to 9.14 (SD 0.90). Between A1 and A4, the PRE group improved their average SCALE
by 0.93, with the POST group improving by 1.23. Changes in SCALE were not statistically
significant between the groups (p<.05), however SCALE scores for the entire sample
significantly increased over the 6months from A1-A4 (t(13)=-2.686, p=.019, ES=0.56).
4.4.2.4.1 KNEE FLEXOR
As a direct result of the training program, changes in KF strength in the PRE group showed an
increase in isokinetic PT/BW, which approached statistical significance (p=.053, ES=0.69) and
reached statistical significance with an increase in muscle power (p=.004, ES=1.09) after
strength training (Table 2, Figure 2). The POST group had a significant increase in isometric
PT/BW (p=.010, ES=0.40) and muscle power (p=.002, ES=0.38). Over 6months from A1 to A4,
KF strength measures showed statistically significant increases in the PRE group for isometric
PT/BW (p=.035, ES=0.83), isokinetic PT/BW (p=.008, ES=0.88) and muscle power (p=.010,
ES=1.05) (Table 2, Figure 2). Both groups displayed a general increase in isokinetic PT/BW and
muscle power measures, between group changes did not differ statistically from each other
(p>.05).
4.4.2.4.2 KNEE EXTENSOR
The PRE group displayed no significant change in any strength variable for KE on completion of
the strength training (p>.05). The POST group displayed significant improvements in isokinetic
PT/BW (p=.033, ES=0.28) and (p=.009, ES=0.42) (Table 2, Figure 2). Over 6 months from A1 to
A4, both the POST and PRE groups showed statistically significant increases in KE isometric
PT/BW (PRE p=.017, ES=1.08, POST: p=.003, ES=0.34).
Likewise, muscle power also
approached a significant increase in the POST group (p=.052, ES=0.33), and reached
significance for the PRE group (p=.025, ES=0.28). The PRE group had a significant increase in
isokinetic PT/BW (p=.004, ES=0.86). Changes in KE strength over 6 months did not statistically
differ statistically between the POST and PRE group (p>.05) (Table 2, Figure 2), although there
was a tendency for the PRE group to display increased change scores across all variables of KE
strength.
89
Table 2 Mean change in strength and muscle volume scores for both PRE (A1-A2) and POST (A3-A4) groups over
their respective 10weeks of strength training and 6month intervention of strength training and BoNT-A (A1-A4).
#
ES=effect size, SD=standard deviation. *Denotes significance, p<.05, denotes approaching significance, p<.06.
Isometric Pk
Torque
(Nm/kg)
Isokinetic Pk
Torque 60°/s
(Nm/kg)
Isokinetic
Power 60°/s
(Watts)
Isometric Pk
Torque
(Nm/kg)
Isokinetic Pk
Torque 60°/s
(Nm/kg)
Isokinetic
Power 60°/s
(Watts)
Gastrocnemius
(kg)
Tibialis Anterior
(kg)
HS Volume
3
(cm /cm)
Quad Volume
3
(cm /cm)
PF Volume
3
(cm /cm)
DF Volume
3
(cm /cm)
PRE
POST
PRE
POST
PRE
POST
PRE
POST
PRE
POST
PRE
POST
PRE
POST
PRE
POST
PRE
POST
PRE
POST
PRE
POST
PRE
POST
Mean group
T value, P Value,
change (10 wks)
ES
Knee Flexor Strength
20.04
t=-1.243, p=.233,
SD 39.40
ES=0.64
17.23
t=-2.949, p=.010,
SD 23.39
ES=0.40*
18.02
t=-2.126, p=.053,
#
SD 37.71
ES=0.69
4.22
t=-1.298, p=.076,
SD 13.82
ES=0.13
4.19
t=-3.554, p=.004,
SD 4.41
ES=1.09*
2.59
t=-3.869, p=.002,
SD 2.68
ES=0.38*
Knee Extensor Strength
29.26
t=-1.318, p=.210,
SD 83.09
ES=0.44
17.94
t=-1.743, p=.102,
SD 41.17
ES=0.16
26.97
t=-1.555, p=.114,
SD 64.90
ES=0.53
21.04
t=-2.341, p=.033,
SD 35.95
ES=0.28*
3.44
t=-1.473, p=.164,
SD 8.74
ES=0.65
4.49
t=-3.015, p=.009,
SD 5.96
ES=0.42*
Isometric Muscle strength
2.46
t=-1.336, p=.204,
SD 3.03
ES=0.30
5.74
t=-3.299, p=.004,
SD 4.58
ES=0.83*
2.46
t=-3.037, p=.010,
SD 3.03
ES=0.91*
1.78
t=-1.819, p=.085,
SD 1.99
ES=0.67
Muscle volume
0.68
t=-4.168, p<.001,
SD 0.55
ES=0.33*
0.39
t=-3.715, p<.002,
SD 0.42
ES=0.42*
0.98
t=-4.249, p=.001,
SD 0.87
ES=0.26*
0.83
t=-7.240, p<.001,
SD 0.44
ES=0.45*
0.85
t=-5.232, p<.001,
SD 0.61
ES=0.73*
0.77
t=-8.114, p<.001,
SD 0.38
ES=0.48*
0.18
t=-4.877, p<.001,
SD 0.14
ES=1.43*
0.15
t=-5.810, p<.001,
SD 0.11
ES=0.62*
Mean group
change (A1-A4)
T value, P Value,
ES
27.72
SD 43.97
13.75
SD 29.97
22.95
SD 27.67
4.41
SD 27.42
4.11
SD 5.07
2.02
SD 5.39
t=-2.359, p=.035,
ES=0.83*
t=-1.835, p=.086,
ES=0.27
t=-3.103, p=.008,
ES=0.88*
t=-0.644, p=.530,
ES=0.12
t=-3.030, p=.010,
ES=1.05*
t=-1.499, p=.155,
ES=0.27
66.20
SD 90.32
36.41
SD 42.03
52.19
SD 56.58
21.39
SD 46.48
6.05
SD 8.69
3.47
SD 6.57
t=-2.742, p=.017,
ES=1.08*
t=-3.465, p=.003,
ES=0.34*
t=-3.452, p=.004,
ES=0.86*
t=-1.841, p=.086,
ES=0.29
t=-2.526, p=.025,
ES=0.28*
t=-2.110, p=.052,
#
ES=0.33
3.84
SD 6.70
5.95
SD 6.70
2.20
SD 2.60
3.58
SD 2.18
t=-2.921, p=.012,
ES=0.60*
t=-3.553, p=.003,
ES=0.73*
t=-3.167, p=.007,
ES=1.01*
t=-6.566, p<.001,
ES=1.18*
0.49
SD 0.46
0.60
SD 0.40
1.63
SD 0.84
1.82
SD 1.18
0.78
SD 0.99
1.01
SD 0.35
0.23
SD 0.21
0.24
SD 0.15
t=-3.962, p=.002,
ES=0.24*
t=-5.920, p<.001,
ES=0.54*
t=-7.261, p<.001,
ES=0.44*
t=5.984, p<.001,
ES=0.94*
t=-2.950, p<.011,
ES=0.35*
t=-11.591,
p<.001, ES=0.59*
t=-4.084, p=.001,
ES=0.82*
t=-6.193, p<.001,
ES=0.88*
90
4.4.2.4.3 ISOMETRIC ASSESSMENT OF TIBIALIS ANTERIOR AND GASTROCNEMIUS
As a direct result of the training program, the PRE group showed statistically significant
increases in the isometric strength tibialis anterior (p=.010, ES=0.91), whilst the POST group
had a statistically significant increase in isometric strength the gastrocnemius (p=.004,
ES=0.83)(Table 2, Figure 3). Over 6months between A1 and A4, both the PRE and POST groups
significantly increased their isometric strength of the gastrocnemius (PRE: p=.012, ES=0.60,
POST: p=.003, ES=0.73) and tibialis anterior (PRE: p=.007, ES=1.01, POST: p<.001, ES=1.18)
(Table 2, Figure 3).
4.4.2.5 MUSCLE VOLUME
The PRE group had a significant increase in normalised HS muscle volume (p<.001, ES=0.33)
and Quads muscle volume (p=.001, ES=0.26). The POST group also had a significant increase in
HS (p<.002, ES=0.42) and Quads muscle volume (p<.001, ES=0.45) after strength training (Table
2, Figure 2).
Over 6 months, both the PRE and POST group had significant increases in HS muscle volume
(PRE: p=.002, ES=0.24, POST: p<.001, ES=0.54) and in Quads muscle volume (PRE: p<.001,
ES=0.44, POST: p<.001, ES=0.94) following strength training (Table 2, Figure 2). Changes in
quads muscle volume over 6 months were significantly different between groups
F(1,14)=4.892, p=.044, ES=0.52), with the POST group showing a larger increase (Figure 2).
In the lower leg, the PRE group had a significant increase in the normalised PF (p<.001,
ES=0.73) and the DF (p<.001, ES=1.43) muscle volume after strength training. The POST group
also showed a significant increase in normalised PF (p<.001, ES=0.48) and DF (p<.001, ES=0.62)
(Table 2, Figure 3).
91
Figure 2 Mean scores for the Knee Flexor (KF) and Knee Extensor (KE) strength, and the
Hamstring (HS) and Quadriceps (Quads) muscle volumes for the PRE and POST group over
assessment time points. The dashed line represents the timing of BoNT-A injection.
*Denotes significance at p<.05, **denotes significance at p<.001.
Over 6 months both the PF and DF increase in MV was significant for the PRE group (p<.011,
ES=0.35, and p=.001, ES=0.82), and POST group (p<.001, ES=0.59, p<.001, ES=0.88), with no
overall difference in muscle volume between the groups across the 6 months.
92
Figure 3 Mean scores for Gastrocnemius and Tibialis Anterior strength, and the Plantar
Flexor (PF) and Dorsi Flexor (DF) muscle volumes for the PRE and POST group over
assessment time points. The dashed line represents the timing of BoNT-A injection.
*Denotes significance at p<.05, **denotes significance at p<.001.
4.5 DISCUSSION
In the treatment of children with CP it is becoming increasingly apparent that the impairments
of the muscle, spasticity and strength, should be considered together. A number of studies
have advocated a multidisciplinary approach to spasticity reduction and specific muscle
strengthening in the management of children with CP2,
33
however there is a paucity of
evidence available to support this approach. This study investigated the combination of BoNTA therapy and strength training for improved muscle strength and morphology outcomes for
children with CP.
Despite subject normalisation of our strength and morphology data, we frequently report high
standard deviations throughout the study; this is attributable to the large variability of
children, classified as both GMFCS I and II, included in our sample. The spasticity
measurements over the course of this study were in keeping with the current evidence
regarding spasticity management; that is that the BoNT-A injections reduced spasticity21, 22 and
the strength training did not increase it11. Furthermore, our post BoNT-A measures of muscle
strength do not appear to show significant decreases in muscle strength, an observation
reported in previous work done by our research team34. A control period, whereby children
93
continued with their normal BoNT-A treatment routine prior to entering the strength
intervention phase, was included in the study. The results from the control period indicate that
with natural growth and standard care programs, children receiving BoNT-A demonstrate
muscle growth and increases in strength. However, after the addition of strength training,
greater arrays of strength gains as well as increases in muscle volume were shown. Consistent
with previously published literature12, 13, each of the muscle groups targeted in the strength
training program had significant strength improvements. To our knowledge this is the first
study to purposefully apply strength training in conjunction with the best practice of BoNT-A
therapy, making these findings even more relevant for clinical decision making. Of particular
interest are the increases measures of the gastrocnemius and the knee flexor strength after
the strength training comparative to the control period. This is of particular importance, as the
gastrocnemius and the HS muscles are frequently targeted for BoNT-A injection in this group
of children. It is widely considered that the general principal for strength training is to weaken
the overactive spastic muscle with BoNT-A, and target the antagonist muscle for
strengthening. Given the positive response in the injected muscles to training, and
corresponding increases in morphology, perhaps future strength training should be targeting
the injected muscles.
A particular point of investigation pertinent to clinicians was the timing of strength training in
relation to the BoNT-A injections, an aspect that to authors’ knowledge, has not been formally
considered throughout the literature. The timing of strength training in relation to BoNT-A
treatment was also considered in this study. All of the children involved in this study showed
strength gains regardless of what when they received the strength training. The overall
outcomes (6 months) did not indicate any significant differences in muscle strength between
the groups; thus one training regime did not result in a statistically significant superior
improvement compared to the other. However, closer analysis of the results revealed
emerging trends between the two groups that may have future application. In the immediate
(10 week) response to strength training, the POST group consistently displayed a greater
capacity for changes of strength, having the most significant increases across the assessed
muscles. However the PRE group displayed greater changes at 6months. These two methods of
assessing change in strength, as the immediate change or the change over 6 months, indicate
opposing stories.
This can be explained when we consider the role of BoNT-A (and spasticity) over the course of
the study; with the PRE group commencing approximately 3 months after their last injection
94
(and at higher levels of spasticity) comparative to the POST group commencing approximately
4weeks after BoNT-A. Perhaps the (POST group) children who trained with BoNT-A active in
their system (and lowered levels of spasticity), had an improved ability to train, possibly a
greater range of movement, and may have also felt less fatigued at the time of training. It may
be argued that these children’s pre-training strength may have simply started at a lower level
because of the BoNT-A, but this was not the case as there were no significant drops in strength
following BoNT-A. As for the greater improvements that were seen over the 6months in the
PRE group, it is possible that after the BoNT-A had acted upon spasticity, the true strength
gains from training prior to the BoNT-A were shown, and that perhaps this group of children
were better equipped to reinforce their strength gains in activities over this time.
Although none of the children in the study undertook any new or intensive interventions
throughout the ‘normal care routine’ period, we did not control the exercise and activities they
participated in. It is common that strength training of some form is incorporated as part of a
child’s standard care, and it would have been un-ethical for us to direct them to not to do so in
this time period. Therefore changes over 6months can not only be attributable to 10 weeks of
strength training, but also from any activities and exercises undertaken in the weeks after
BoNT-A. In saying this, it should be noted that there were far fewer significant changes in
strength for children over the ‘normal care routine’ time periods.
Comprised of movement repetition and progressing loads, the strength training program in
this study addressed both neural and structural factors of muscle strength. Whilst it is likely
that improvements in motor unit recruitment could be a factor behind the strength gains, we
did not measure muscular activation per se; however our measure of selective motor control
did indicate a significant improvement over the course of the study. Muscle volume was
measured, and corresponding with strength gains were significant increases in muscle volumes
of the HS, Quads, PF and DF muscle groups. The muscle hypertrophy following strength
training is consistent with previous research20, and in addition also seen with the simultaneous
use of BoNT-A therapy. It should be noted that increased muscle volumes, most likely
attributable to natural growth, are also shown over the ‘normal care routine’ period, in
particular for the quadriceps and gastrocnemius in the POST group. What needs to be
considered is that whilst natural growth, as measured in the ‘normal care’ period, may afford
an increase in muscle volume over time, is this increase enough, and do they match those of
their typically developing peers? This is important to consider, with Barber and Colleagues
(2011)35 suggesting that deficits in muscle volume may increase in the individual with spastic
95
CP as he or she grows older. Therefore, the gains strength training may offer may be even
more advantageous in an adolescent population.
The small sample size is a limitation of this study; however a post hoc power analysis based on
the strength results in the current study revealed an average power of 0.88 to detect a
meaningful difference over the intervention (alpha = 0.05). With small numbers, the inclusion
of a larger control group (of BoNT-A only) and of an additional control group (of strength
training only) was not possible, however we encourage further research with access to a larger
sample of participants to investigate this. Our study was strongly influenced by clinical
practice, which in itself also brought about certain limitations to the study; we did not prohibit
children from participating in their usual physiotherapy (often including some form of strength
training) in the ‘normal care periods’, we could not standardise the muscles being injected
with BoNT-A, and we could not monitor each home session to ensure that training was
performed at an optimal level. However these factors are also an advantage in that it means
that our research results are highly clinically relevant.
With the combination of neural and structural factors improving muscle strength, and the
reduction of spasticity from BoNT-A, the functional outcome for children in this study was
overwhelmingly positive. Scores from the GAS demonstrate that over the 6 months of this
study, the combination of BoNT-A and strength training children were able to achieve their
functional goals, with both groups significantly increasing their measure of GAS. This is possibly
the most important outcome of this clinical study, when the overreaching aim of therapy is
commonly directed towards improved functional ability36.
Consistent with recent systematic reviews4, 11 this research has provided further evidence that
strength training can improve muscle strength in children with CP, which can be associated
with hypertrophy20. The morphology results could indicate the potential role of strength
training in altering the rate of muscle growth, in an aim to improve the failure of muscle
growth associated with CP37. What makes this study distinct is that strength training was
administered in combination with BoNT-A therapy, and demonstrated that the concurrent
treatment could achieve positive outcomes in terms of strength, spasticity and function. It has
shown that muscles injected with BoNT-A can be successfully strengthened. We endeavoured
to find if timing of strength training, in relation to BoNT-A would indicate a preference for
better outcomes, and found that both groups made significant improvement that did not differ
96
significantly between groups. However, it did appear that the POST BoNT-A training group
were able to utilise their increased muscle volume immediately, whereas the PRE group
required their spasticity to be masked before their true strength gain could become apparent.
4.6 CLINICAL IMPLICATIONS
Home based strength training, based on a child’s individual goals has been shown to be
successful in improving strength and goal attainment in this study. This has been combined
with BoNT-A therapy to target both muscle weakness and muscular spasticity in children with
CP and has confirmed that either PRE or POST BoNT-A strength training may be individually
adapted to suit the needs of the child for a successful outcome. PRE training may be more
suitable for a child scheduled to receive serial casts following BoNT-A, whereas, POST BoNT-A
training may be more appropriate in order to achieve immediate results for functional goals
for some children. The muscles targeted in the strength training should include those injected
by BoNT-A, with the results of this study demonstrating significant strength improvements in
injected muscles. CP management is a lifelong challenge that requires therapists and clinicians
to consider, and treat, the impairments affecting the child holistically. This study provides
evidence for the successful combination of both BoNT-A therapy and strength training, over
and above BoNT-A therapy alone. The potential economical benefit of combining therapies to
maximise outcome should also be considered in the future.
The authors would like to thank the Department of Paediatric Rehabilitation, PMH for their
support and assistance with recruitment, the Department of Diagnostic Imaging, PMH for their
assistance and knowledge in data collection and the contribution of the School of Sport
Science, Exercise & Health at UWA for the use of equipment and facilities. Sincere thanks to
Tania Shillington, Bree Dwyer and Martin Spits for their role with data collection, Nadine Smith
for her input, and the children and families who volunteered to participate in this study.
97
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Lippincot, Williams & Wilkins; 2006.
33.
34.
Williams SA, Reid SL, Elliott CM, Shipman P, Valentine J. Morphological alterations in
spastic muscles immediately following Botulinum Toxin Type-A treatment in children with
Cerebral Palsy. Unpublished observations. 2012.
35.
Child Neurol. 2011;53:543-8.
36.
Shepherd R, editor. Cerebral palsy in: Physiotherapy in paediatrics. Oxford:
Butterworth-Heinemann; 1995.
37.
Lampe R, Grassl S, Mitternacht J, Gerdesmeyer L, Gradinger R. MRT-measurements of
muscle volumes of the lower extremities of youths with spastic hemiplegia caused by cerebral
palsy. Brain Dev. 2006;28:500-6.
100
CHAPTER FIVE
IMPROVING THE GAIT OF CHILDREN WITH CEREBRAL PALSY USING THE
COMBINED INTERVENTIONS OF STRENGTH TRAINING AND BOTULINUM
NEUROTOXIN TYPE-A.
This manuscript was submitted for publication into the journal, Gait and Posture, in July 2012.
Williams S, Elliott C, Valentine J, Reid S. Improving the gait of children with Cerebral Palsy using
the combined interventions of strength training and Botulinum Neurotoxin Type-A. Gait
Posture. 2012. In review.
The PhD candidate, Sîan A Williams accounted for 80% of the intellectual property associated
101
FOREWORD
The previous paper provided evidence for the successful combination of both Botulinum
Neurotoxin Type-A (BoNT-A) therapy and strength training, over and above BoNT-A therapy
alone. In addition to this, it demonstrated the combination of therapies to successfully
improve the attainment of individual functional goals, set by the children in the study.
Spasticity and muscular weakness are two impairments known to negatively impact walking
ability in children with CP. This paper investigates the effect of the combined BoNT-A and
strength training intervention on walking gait, with three-dimensional motion analysis. The
Gait Deviation Index is used as a global measure of gait compared to non-pathological gait,
joint kinetics of the hip, knee and ankle joint are also compared with an age-matched typically
developing population. This paper provides novel information endorsing the combined use of
BoNT-A and strength training for superior outcomes of gait.
102
5.1 ABSTRACT
This study investigated the combined effects of strength training and Botulinum Neurotoxin
Type-A (BoNT-A) on walking gait in children with CP. Fifteen children receiving BoNT-A for
spasticity management, classified as Spastic Diplegic, GMFCS I-II, aged 5-12years (mean=8.52)
participated in the study. Children were randomly allocated to 10 weeks of strength training
either before or after BoNT-A, assessed twice over 6months. Eight of the 15 children also
completed a control period of BoNT-A treatment only. Hamstring and gastrocnemius muscles
were injected with BoNT-A as clinically indicated. Three-dimensional gait analysis determined
the Gait Deviation Index (GDI) and kinetic profiles at hip, knee and ankle joints. During the
intervention period, GDI significantly increased from 79.28 to 85.28 (p=.014, ES=0.65). Peak
power generated at the hip significantly decreased; 2.31W/Kg to 1.39W/Kg (p=.002, ES=0.88),
as did the knee peak power; 1.64W/Kg to 1.05W/Kg (p=.015, ES=0.62), with no change at the
ankle. Absorption at the knee decreased; 26.77W/Kg to 14.83W/Kg (p=.001, ES=0.92). The
combination of strength training with BoNT-A treatment indicated a positive impact on
kinematic and kinetic profiles, resulting in more efficient use of energy transfer to drive
forward locomotion.
KEYWORDS: Cerebral Palsy, strength training, Botulinum Toxin, Muscle Weakness, spasticity,
gait.
103
5.2 INTRODUCTION
Spasticity and muscular weakness are primary motor impairments associated with Cerebral
Palsy (CP). Together with increased muscle co-activation and impaired selective motor control,
these impairments are responsible for disturbed movement patterns in walking and other daily
life activities1. Inefficient ambulation, commonly targeted in therapeutic goals2, is one of the
most significant functional limitations of CP3.
Recent reports consider muscle weakness to be directly related to gross motor function and
gait4, 5. Strength training is recognised as an effective intervention for improving muscular
strength in children with CP6, with strength improvements translatable to gains in motor
function6-8. Changes in gait kinematics has been reported with improvements in strength
including; a more upright posture9, improved hip and knee extension9-12 and trends of
improved ankle dorsi-flexion11, however few studies report gait kinetics following
strengthening in the CP population. Engsberg and Colleagues (2006)11 reported inconclusive
kinetic alterations following strength training, suggesting that future research should include
the calculation of power. Defined as the work performed per unit of time, power may be used
to document the net energy generation or absorption of the muscles during activity 13.
Strengthening of the muscles is more likely to result in changes in the muscles force profiles
than to alter kinematic profiles; investigating power may be a more effective method of
evaluating the impact of strengthening.
During typical gait, the ankle plantar-flexors act as the greatest contributors to forward
propulsion14. In CP gait, particularly in kinetic variables at the ankle, muscle strength is linked
with gait patterns5. Eek and Colleagues (2011)5 have also surmised that adequate strength
around the hip and knee joints is needed for stability to allow plantar-flexor power generation
at push off5. Considering the essential nature of the bi-articular plantar-flexors in locomotion,
and the impaired function of these muscle groups in CP, it is important to understand the
potential impact of treatment interventions targeting these muscle groups.
Botulinum Neurotoxin Type-A (BoNT-A) is an established treatment for spasticity management
in CP15. Along with benefits of reduced muscle tone16, research reports improvements in range
of joint motion16, functional measures17-19, 20, and gait patterns16; with increases in ankle dorsiflexion21-23, knee extension21, and a normalisation of ankle kinetics21. Zurcher and Colleagues
(2001)21 evaluated kinetics at the ankle in children with CP after BoNT-A injections, reporting
104
increased power during gait. BoNT-A and strength training both appear to have a positive
impact on gait in children with CP, therefore it could be assumed that the combination of the
therapies would also further improve gait function. The purpose of the present study was to
investigate whether a combination of BoNT-A and strength training can improve walking gait in
children with CP.
5.3 METHODS
5.3.1 PARTICIPANTS
Ten boys and five girls with spastic diplegia, classified as Gross Motor Function Classification
System (GMFCS) level I-II participated in this study. The children had a mean age of 8years 5mo
(SD 1yr 10 mo, range 5-12yrs), average height of 129.87cm (SD 10.92cm) and weight of
27.97kg (SD 7.43kg). No child had a history of lower limb surgery, nor had undergone serial
casting in the previous six months. Ethical approval for the study was obtained from the Ethics
Committee of PMH (1766), and from the University of Western Australia. Written consent was
obtained from the parents of all the participants.
All 15 children were receiving BoNT-A treatment for spasticity management, and had already
received a minimum of two series of BoNT-A prior to the study (maximum series=15, mean
series=8.93). The muscle(s) selected for injection were based on clinical assessment and
functional goal setting, the total dose of BoNT-A (Botox®, Allergan, Irvine, CA, USA) was
gastrocnemius' (30 legs injected; 2-6U/kg), five participants also received BoNT-A to bilateral
medial hamstrings (10 legs; 2-4U/kg). Other muscles injected included the soleus (4legs; 12U/kg) adductors (2 legs; 1U/Kg), rectus femoris (2 legs; 1U/Kg), and tibialis posterior (1 leg;
1U/Kg). No child had more than three muscles per leg injected.
For comparison, average power profiles from a convenience sample of 16 typically developing
(TD) children were used. Demographic characteristics of the TD children did not differ
significantly from the CP group; 10 males, 6 females, mean age; 7yrs 5mo (SD 1yr 5mo, range
4-11yrs), average height; 122.50cm (SD 12.16), and average weight; 24.04kg (SD 5.74).
105
5.3.2 PROCEDURES
The study design, dictated by clinical care, utilised a randomised cross-comparison design with
a 6month pre-intervention baseline serving as a control period (Figure 1). For the control
period, eight children completed assessments 12-14 weeks before their scheduled BoNT-A
injection (B) and continued to receive normal clinical care both before and for 12 weeks after
that injection. These eight, together with a further seven children were block randomised by
age, gender and GMFCS level into either a PRE or POST BoNT-A strength training group. The
PRE group completed strength training in the 10 weeks leading up to BoNT-A, and the POST
group completed the training after BoNT-A, commencing approximately 5 weeks (SD 1week,
range 3-6 weeks) after the injection. In the alternative weeks they continued with their normal
care routine. Children completed two assessments; Assessment 1 (A1) timed approximately 12
weeks prior to their scheduled BoNT-A injection and Assessment 2 (A2) approximately 14
weeks post injection.
A1
BoNT-A
B
Normal Care
Routine
Normal Care
Routine
Control Period n=8
W-26
W-12
W0
A2
BoNT-A
PRE strength
training
Normal Care
Routine
Normal Care
Routine
POST strength
training
W12
W26
Figure 1 Cross-comparison study design, with a pre-intervention baseline assessment (B) for
8 participants forming a control period, and 15 children completing the intervention period.
Vertical dashed lines represent the timing of Botulinum Toxin injections
5.3.2.1 3D CLINICAL GAIT ANALYSIS (3DGA)
Three-dimensional gait analysis (3DGA) was performed using two AMTI force platforms
(2000Hz) and Vicon® (250Hz, MX system Oxford metrics, UK), allowing for the collection of
kinematic and kinetic data. Retro-reflective markers were placed on each participant in
accordance with the University of Western Australia’s lower limb 3DGA protocol24. Participants
were asked to walk barefoot in their usual manner along a 10 meter walkway to capture five
successful trials (upon where a clean foot strike on a force platform was achieved)
representative of the child’s usual gait pattern.
The Gait Deviation Index (GDI)25 utilises information from 3DGA to provide a better global
understanding of the overall gait pathology. The GDI compares nine kinematic variables of a
106
subject's gait against those of a control group. This method of comparison aims to reflect the
extent of gait variation; a GDI score of 100 (+/- 10) denotes non-pathological gait, and each 10
point decrement below 100 indicates 1 standard from normal kinematics25. All graphs obtained
from 3DGA were normalised as a percentage of the gait cycle; a representative trial for each
participant was input into the electronic addendum provided with the GDI paper (using the
control data provided)25.
Joint kinetics (power) was calculated using inverse dynamics, and normalised to body weight
to permit between subject comparisons. Power profiles for hip, knee and ankle joints in the
sagittal plane were calculated for bilaterally. Peak power generation (maximum positive value)
and power absorption were used for analysis. Power absorption was defined as the sum of the
area under the curve (using the Trapezoidal Rule for integration26) in the stance phase of the
gait cycle.
5.3.2.2 TRAINING PROGRAM
Participants completed a home based progressive strength training program, training three
times a week for 10weeks. Program coordination and progression was conducted fortnightly
by a visiting exercise physiologist, with remaining sessions conducted by a trained family
member. Each session included manual and passive stretching of the lower limb muscle
groups. The design of the program was based on the child’s initial strength assessment and
individual functional goals and was progressed in accordance with guidelines27. Exercises were
performed in three sets bilaterally, with adequate rest between sets. Further details of the
strength program are detailed elsewhere28.
5.3.3 DATA ANALYSIS
Analysis A: To estimate changes in gait over the control period (B to A1), the mean and 95%
confidence interval of within-subject change of each outcome score was calculated. A
descriptive comparison of measures of joint power between the CP and TD children is also
included. Statistical significance was assessed with a 2-tailed T-test, and considered significant
if p<0.05.
Analysis B: To estimate whether the timing of the strength training preceding or following
BoNT-A resulted in a differential outcome, the mean within-subject change of each score over
107
the intervention period for the PRE group was compared with the POST group. The mean
within-subject change of each score over the intervention period for the total cohort of
children was calculated to estimate the effect of strength training, independent of timing. A
descriptive comparison of measures of joint power for the CP and TD sample of children is also
included. Effect sizes were determined using Cohen’s d equation29.
5.4 RESULTS
5.4.1 ANALYSIS A: CONTROL GROUP (N=8 CHILDREN)
5.4.1.1 GDI
During the control period there was no statistically significant change in group mean GDI score
(t(15)=0.413, p=.685, ES=0.01); from an average of 84.77 (SE 2.12, range: 69.25-97.92), to
83.72 (SE 2.41, range: 69.64-98.23).
5.4.1.2 POWER PROFILE
5.4.1.2.1 HIP JOINT
Peak power generated at the hip joint increased significantly over the control period (t(15)=2.518, p=.023, ES=1.09), bringing the group average from 1.44W/Kg (SE 0.15), to 2.45W/Kg (SE
0.32), higher than the TD average hip peak joint power (2.05W/Kg, SE 0.25). Power absorption
did not change significantly (t(15)=1.452, p=.167, ES=0.66), and was larger than the TD average
(8.82W/Kg, SE 0.87) (Figure 2).
5.4.1.2.2 KNEE JOINT
Peak power generated at the knee joint increased significantly over the control period (t(15)=3.293, p=.005, ES=1.39), bringing the group average from 0.97W/Kg (SE 0.09) to 2.11W/Kg (SE
0.33), larger than that of the TD (1.53W/Kg, SE 0.10). Power absorption had an increasing
trend, from 18.36W/Kg (SE 2.26) to 29.36 (SE 4.36), but was not statistical significance
(t(15)=1.946, p=.071, ES=0.83), yet was evidently larger than the TD average (8.91W/Kg, SE
0.87) (Figure 2).
108
5.4.1.2.3 ANKLE JOINT
Peak power generated at the ankle joint increased significantly over the control period (t(13)=2.763, p=.016, ES=0.61), from 1.78W/Kg (SE 0.33), to 2.55W/Kg (SE 0.32), below the TD
average (3.45 W/Kg, SE 0.13). Power absorption at the ankle joint showed no significant
change (t(15)=0.056, p=.956, ES=0.02), but was higher than the TD value (8.04W/Kg, SE 0.66)
(Figure 2).
Figure 2 Average power generation (peak), and power absorption (area) at the hip, knee and
ankle joints through stance, before and after a control period (of BoNT-A with normal clinical
care) for eight children. Dashed vertical lines represent the BoNT-A injection, horizontal solid
lines indicate the average from the typically developing population and the * denotes a
signifcant increase p<.05
109
5.4.2 ANALYSIS B: INTERVENTION GROUP (N=15 CHILDREN)
5.4.2.1 GDI
Over the intervention, the grouped mean GDI scores significantly increased (t(29)=-2.601,
p=.014, ES=0.65), as did scores for the POST group (t(15)=-2.165, p=.047, ES=0.49). The PRE
group did not increase significantly, (t(13)=-1.493, p=.159, ES=0.65) (Table 1).
Table 1 Mean within-subject changes of the Gait Deviation Index (GDI), and the Hip, Knee
and Ankle joint power generation and absorption over 6months of the PRE group (training
before BoNT-A), of the POST group (training after BoNT-A), and of the entire CP cohort.*
Significance at p<.05. Relative scores for our typically developing sample (TD) of children are
also included for reference.
TD score
(SE)
GDI
Hip
Joint
Knee
joint
Ankle
joint
Power
Generation
(W/Kg)
Power
Absorption
(W/Kg)
Power
Generation
(W/Kg)
Power
Absorption
(W/Kg)
92.29
(1.28)
2.05
(0.25)
8.82
(0.87)
1.53
(0.10)
8.91
(0.87)
Power
Generation
(W/Kg)
3.45
(0.13)
Power
Absorption
(W/Kg)
8.04
(0.66)
Group
Initial score (SE)
Change after
6months (SE)
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
81.34 (2.64)
77.48 (3.47)
79.28 (2.22)
1.85 (0.22)
2.74 (0.30)
2.31 (0.20)
10.85 (1.46)
12.00 (1.70)
11.44 (1.13
1.39 (0.23)
2.04 (0.33)
1.74 (0.30)
24.06 (1.17)
29.15 (0.79)
26.77(3.08)
2.35 (0.36)
2.12 (0.26)
2.24 (0.22)
8.09 (0.09)
9.03 (0.27)
8.59 (1.10)
5.59 (3.75)
6.34 (2.93)*
5.99(2.30)*
-0.83 (0.31)*
-0.98 (0.43)*
-0.91 (0.26)*
-3.66 (2.57)*
-5.80 (1.52)
-4.43 (1.53)*
-0.42 (0.44)
-1.01 (0.33)*
-0.72 (0.27)*
-12.94 (4.47)*
-11.77 (4.58)*
-11.58 (3.26)*
-0.61 (0.66)
-0.57 (0.32)
-0.59 (0.36)
0.54 (1.71)
-1.97 (1.55)
-0.63 (1.19)
5.4.2.2 POWER PROFILE
5.4.2.2.1 HIP JOINT
The cohort mean peak hip power decreased significantly (t(29)=3.434, p=.002, ES=0.88) over
the intervention period to below the TD average. Both the PRE (t(13)=2.652, p=.020, ES=1.13)
and POST (t(15)=2.279, p=.039, ES=0.88) groups significantly decreased hip joint power
generation.
110
Power absorption significantly decreased at the hip joint (t(29)=3.044, p=.005, ES=0.85) for the
entire cohort, to an average below the TD sample. The PRE group displayed a significant
decrease in hip joint power absorption (t(13)=3.808, p=.002, ES=1.44), however the POST
group did not (t(15)=1.426, p=.174, ES=0.58) (Table 1, Figure 3).
5.4.2.2.2 KNEE JOINT
At the knee joint, a significant decrease in joint power generation for the entire cohort was
observed over the intervention (t(29)=2.585, p=.015, ES=0.62), to an average below the TD
score. The PRE group did not show a significant change in knee peak power generation
(t(15)=0.943, p=.363, ES=0.38), whilst the POST group significantly decreased over the
intervention (t(15)=2.916, p=.011, ES=0.88).
Knee power absorption significantly decreased for the entire cohort over the intervention
(t(29)=-3.668, p=.001, ES=0.92), but remained comparatively larger than the TD average.
The POST group significantly decreased power absorption at the knee joint (t(15)=-2.41,
p=.029, ES=0.79), as did the PRE group (t(13)=-2.706, p=.018, ES=1.17) (Table 1, Figure 3).
5.4.2.2.3 ANKLE JOINT
There was no significant change in peak ankle power generation for the entire cohort
(t(29)=1.653, p=.110, ES=0.36), the PRE (t(13)=1.811, p=.093, ES=0.38) or POST group
(t(15)=0.931, p=.369, ES=0.33).
Power absorption at the ankle joint did not change significantly over the intervention period
for the entire cohort (t(29)=0.670, p=.508, ES=0.12), PRE (t(13)=-0.293, p=.774, ES=0.09) or
POST group (t(15)=1.269, p=.244, ES=0.27),(Table 1,Figure 3).
111
Figure 3 Average power generation (peak), and average power absorption (area) at the Hip,
Knee and Ankle joints through the stance phase of gait for the children in the PRE and POST
group, and of all the children in the study grouped together. Dashed vertical lines represent
the BoNT-A injection, whilst the solid horizontal line indicates the average of the typically
developing group.
5.5 DISCUSSION
This paper has investigated the outcomes of the combined treatments of BoNT-A and strength
training on walking gait. Whilst children showed no change in GDI over the control period,
significant increases were measured over the intervention. Initial GDI scores reveal that our
sample of children, classified as GMFCS I’s and II’s, were already walking at a high functional
level, with an average score of 79.28 (SE 2.22), where 100 (+/-10) denotes non-pathological
gait25. The fact that these children could show significant improvements in this global measure
of gait is positive, highlighting the possibilities for interventions in higher functioning children
with CP. We believe the changes in GDI from the combined interventions, though small, to be
112
clinically important. Whilst the GDI provides a practical global reflection of gait calculated from
kinematic variables, the use of kinetic variables can provide a better understanding of how
each joint is functioning during gait.
Previous research has linked muscle strength and kinetics in the CP population, with a focus on
the ankle at toe-off (power generation)5. This study showed the combination of lower limb
strength training with BoNT-A treatment to alter joint power outputs at the hip and knee. In
contrast to increasing trends over the control period, levels of power generated at the hip joint
decreased over the intervention, as did levels of power absorption at the knee joint, to levels
more closely matching the TD population. Matched with the measured improvements in GDI,
perhaps this indicates an improved efficiency of muscles working to facilitate gait, and that the
intervention may have promoted better motor recruitment and activation strategies. Strength
training, coupled with the BoNT-A treatment in the plantar flexors may have served to increase
dorsi-flexion and knee extension range of motion21-23, resulting in better limb positioning for
more effective absorption and production of power. This theory is supported by the reduced
power absorption measured at the knee joint, possibly reflective of reduced knee flexion
throughout gait9, 10, 11. Unlike the hip and ankle, the role of the knee joint in gait is not for
driving forward locomotion, but rather to act as a power transfer agent between the ankle and
hip; a reduction in loading at the knee may be protective against longer term injury and pain.
In light of the decreases in both knee power generation and absorption over the intervention
period, compared to the increasing trends over the control period, we suggest that the
combination of strength training and BoNT-A facilitated a more efficient power transfer
through the muscles of the lower limb.
Within the CP population, literature has observed a general shift in power generation from the
ankle to the hip joint through walking gait5, 30. Similar to Eek et al.,(2011)5, this study measured
decreased power generation (peak power in at terminal stance) around the ankle joint in the
children with CP, but in contrast we did not measure greater values of peak power generation
at the hip joint5. However, here we have reported values of peak power, whereas Eek et al.,
(2011)5 reported power summation.
The combined interventions of BoNT-A and strength did not alter power generation at the
ankle joint. This is not altogether unexpected, reflective of the strength training administered
in this study and the muscles targeted for BoNT-A. Due to varying degrees of contracture, and
113
personalised goals, muscles around the ankle were not targeted as frequently for
strengthening, whereas every child trained muscles around the hip and knee. Whilst strength
in the ankle plantar flexors is important in gait14, and are a commonly targeted muscle group
for BoNT-A treatment in diplegic CP, the strength of the muscles around the hip and knee
joints are also considered to be important for improving gait, providing stabilisation for
effective push off at the ankle5, 31.
The timing of strength training in relation to BoNT-A was also considered; in terms of
improvement in the GDI, the POST group measured the greatest changes over the
intervention. We suggest that children training with BoNT-A active in their system (and
lowered levels of spasticity) were able to achieve a greater range of movement throughout
exercises16, and perhaps a better ability to train. In terms of the power produced around the
joints, both groups showed similar declines in power generated at the hip joint, to levels below
our TD sample. The results from this study suggests to clinicians that training after BoNT-A
injections may be more beneficial for achieving a style of walk closer resembling the TD
population, however there appears to be no difference in terms of power generation or
absorption.
5.6 CONCLUSION
These results demonstrate positive changes in gait profiles and kinetics from the combination
of strength training and BoNT-A injections compared with BoNT-A alone. Children with CP
significantly improved their GDI’s, without the need to increase the levels of power generated
at the hip, knee and ankle joints suggesting an improved efficiency of the muscles. Knee
absorption was also significantly reduced during the stance phase of gait. The intervention
improved power profiles at hip and knee joints to levels closely matching the TD sample.
Minimal kinetic changes were demonstrated at the ankle joint, a reflection of the muscles
targeted for strength training. Administering strength training after BoNT-A treatment can
result in superior outcomes for gait.
This project was supported by Princess Margaret Hospital (PMH) Foundation Grant. The
authors would like to thank the Department of Paediatric Rehabilitation, PMH for their support
and assistance with recruitment. Authors would also like to acknowledge the contribution of
114
the School of Sport Science, Exercise & Health at UWA for the use of equipment and facilities.
Sincere thanks go to the children and families who volunteered to participate in this study and
to Nadine Smith (Physiotherapist, PMH) for advice and assistance with the strengthening
program.
115
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118
CHAPTER SIX
THE COMBINATION OF STRENGTH TRAINING AND BOTULINUM
NEUROTOXIN TYPE-A IN CHILDREN WITH CEREBRAL PALSY: THE EFFECT
ON ACTIVITY, PARTICIPATION AND QUALITY OF LIFE
This manuscript was submitted for publication into the journal, Disability and Rehabilitation, in
July 2012.
Williams S, Reid S, Valentine J, Blair E, Smith N, Shillington T, Elliott C. The combination of
strength training and Botulinum Neurotoxin Type-A in children with Cerebral Palsy: The effect
on activity, participation & quality of life. Disabil Rehabil. 2012. In Review
The PhD candidate, Sîan A Williams accounted for 80% of the intellectual property associated
.
119
FOREWORD
The previous two papers have demonstrated the combination of BoNT-A and strength training
to be effective in improving outcomes at the level of body structure and function of the ICF,
over and above BoNT-A therapy in the normal care routine. Chapter four demonstrated
increases in muscle strength and reductions in spasticity, with improved attainment of
individually set functional goals. This was important in that it reflected the success of our
home based strength training (combined with BoNT-A) in the area of body functions and
structures being targeted in the intervention. Chapter five continued within the domain of
body structures and function, and demonstrated the positive effect of the combined
interventions leading to improvements in walking gait. Employing three-dimensional motion
analysis, children demonstrated gait profiles closer resembling that of the non-pathological
populations’ gait, without increases in the required power generated at the hip, knee and
ankle joints. This suggested an improved efficiency of the muscles working to execute gait. The
final paper of this thesis investigates whether the positive changes measured in the body
structures and function level of the ICF, extends to improvements in other aspects of the ICF,
namely in measures of activity, participation and quality of life.
120
6.1 ABSTRACT
Aim: To investigate the combined effects of strength training and Botulinum Neurotoxin typeA (BoNT-A) treatment on activity, participation and quality of life (QoL) in children with
cerebral palsy (CP).
Method: Fifteen children, aged between 5-12 years (mean= 8years 5mo, SD 1yr 10 mo) with
spastic diplegic CP, GMFCS I-II, currently receiving BoNT-A for spasticity management took part
in the study. Children undertook a 10 week individualised lower limb strength training
program, based on the child’s goals. They completed up to 3 sessions weekly, and were
assessed four times over 6 months based around their scheduled BoNT-A injections. Hamstring
and gastrocnemius muscles were injected with BoNT-A as clinically indicated by goal setting
and clinical assessment. Eight of the 15 children took part in a 6month pre-intervention
baseline phase which served as a control group. Activity was assessed via the Timed-Up-andGo (TUG) and the Six Minute Walk Test (6MWT), participation was assessed with the
Assessment of Life Habits for children (LIFE-H), the Canadian Occupational Performance
Measure (COPM) assessed goal attainment across both activity and participation, and the
Cerebral Palsy Quality of Life Questionnaire for Children (CP-QoL) measured QoL.
Results: The intervention resulted in a significant improvement in the TUG (p=.043, ES=0.55),
but no effect on the 6MWT at the level of activity. The LIFE-H indicated increased domains of
relationships (p=.043, ES=1.44), nutrition (p=.017, ES=0.44), and education (p=.037, ES=0.16).
The COPM showed a clinically significant improvement (a score of 2 or above) in parent rated
performance, but not in satisfaction. CP QoL indicated increases in the areas of family health
(p=.023, ES=0.30) and emotional well-being and self-esteem (p=.053, ES=0.29).
Interpretation: By targeting two primary motor impairments of CP; spasticity and muscular
weakness with combined interventions of strength training and Botulinum Toxin Type-A, this
study has demonstrated some positive effects at the levels of activity, participation and QoL. In
view of reports of decreasing participation and QoL over time for children with CP, these
results are encouraging.
KEYWORDS: Muscle weakness, Spasticity, Cerebral Palsy, The ICF, Activity, Participation,
Quality of Life.
121
6.2 INTRODUCTION
In children with cerebral palsy (CP), spasticity and muscular weakness are considered to be
two primary impairments related to motor dysfunction1, which, along with increased muscle
co-activation and impaired selective motor control, are responsible for disturbed movement
patterns in walking and other daily life activities2. Children with CP are also reported to
experience a lower quality of life (QoL)3, 4, and it is suggested they are at risk of experiencing
participation restrictions5, greater activity limitations and are less physically active then their
typically developing peers6-8. The International Classification of Functioning, Disability and
Health (ICF) framework9 across dimensions of body function, activity and participation allows
for a holistic approach to evaluating current and future treatment options. Understanding the
impact of therapeutic interventions on all dimensions of the ICF is imperative for determining
the optimal management of the impairments associated with CP.
For people with diplegic CP, therapeutic goals are often directed towards improving the ability
to walk10. Impairment of walking is significantly associated with reduced participation in most
domains of the Assessment of Life Habits (LIFE-H) questionnaire11. Consistent with previous
literature12-14, a recent study by Calley and Colleagues (2012)15 reported that compared with
typically developing peers, children with CP had difficulties participating in activities across
home, school and in the wider community as a result of restrictions in physical functioning and
mobility, with concomitant reductions in QoL15. Of particular concern to parents and clinicians
is that well-being, a ‘broad notion’ used by researchers that considers QoL16, is generally
reported to be lower amongst children with CP16. Therefore QoL, relating to a person’s
individual perception or feelings of well-being across a number of domains (e.g. physical,
social, emotional, spiritual)17, is an important outcome that needs to be considered in
treatment evaluation.
Botulinum Neurotoxin Type-A (BoNT-A) is an established and commonly utilised treatment for
spasticity management for children with CP18-23
24
with
the reported improvements in muscle
24
tone , range of joint motion and functional measures25, 26, 27. However, BoNT-A treatment
has a limited effect on daily activities28, and there is little information concerning its effects on
participation and QoL. Similarly, little information is available on the effects of strength
training on the activity and participation29. Research has confirmed the benefits of strength
training in children with CP to improve muscle strength29-31, flexibility, posture and balance32,
and has been associated with improvements relating to walking29,
30, 33-36
. Despite this, the
effect of strength training programs on mobility, function, or the ability to participate in
122
normal societal roles remain undetermined29, whilst the impact on QoL, to our knowledge, has
not yet been subjected to controlled assessment. Consequently there is a call for health care
providers to investigate the outcomes of strength and BoNT-A at the ICF levels of activity,
participation and QoL.
Whilst strength training targets muscular weakness, BoNT-A targets muscle spasticity23. Our
previous research has investigated the combined effects of BoNT-A and strength training at
the level of impairment, reporting improvements in spasticity, muscle strength, muscle
morphology, functional goals31 and three-dimensional outcomes of gait37. However, it is
unknown if these benefits at the impairment level translate to improvements in other aspects
of the ICF. Therefore, this study aims to investigate the combination of BoNT-A and strength
training at the activity, participation and QoL domains of the ICF. Furthermore, we investigated
the effects of varying timing of strength training in relation to BoNT-A, administered either
before or after the injection.
6.3 METHODS
6.3.1 PARTICIPANTS
Ten boys and five girls with spastic diplegic CP, classified as Gross Motor Function Classification
System (GMFCS) level I-II were recruited from the Cerebral Palsy Mobility Service (CPMS). All
children matching our inclusion criteria (aged 5-12, GMFCS I-II, classified as spastic diplegic CP,
free of any history of surgery and cognitively able to follow instructions) were identified and
contacted by CPMS to ask if they would like to be contacted about participation in research.
Families that responded were then contacted by the researchers, provided information on this
study and invited to participate. The fifteen participating children had a mean age of 8years
5mo (SD 1yr 10 mo, range 5-12yrs), an average height of 129.87cm (SD 10.92cm) average
weight of 27.97kg (SD 7.43kg) and Body Mass Index of 16.34 (SD 2.4). No child had undergone
serial casting in the previous six months and no child had a history of lower limb surgery.
Ethical approval for the study was obtained from the Ethics Committee of PMH (# 1766), and
from the University of Western Australia. Written consent was obtained from the parents of all
the participants.
All 15 children were receiving BoNT-A treatment for spasticity management bilaterally in their
lower limbs, and had already received a minimum of two series of BoNT-A prior to the
injection series included in the study (maximum=15 series, mean=8.93 series). The muscle(s)
123
selected for injection were determined by the child’s physician based on clinical assessment
and functional goal setting, the total dose of BoNT-A (Botox®, Allergan, Irvine, CA, USA) was
gastrocnemius' (30 legs injected; 2-6U/kg), and five participants also received BoNT-A to
bilateral medial hamstrings (10 legs; 2-4U/kg). Other muscles injected included the soleus
(4legs; 1-2U/kg) adductors (2 legs; 1U/Kg), rectus femoris (2 legs; 1U/Kg), and tibialis posterior
(1 leg; 1U/Kg). No child had more than three muscles injected per leg.
6.3.2 PROCEDURES
The study design, dictated by current clinical care, utilised a repeated measures crosscomparison design with a 6month pre-intervention baseline phase serving as a control period
(Figure 1). For the control period, eight children completed a baseline (B) assessment 12 (+/- 2)
weeks before their next scheduled BoNT-A injection and continued to receive normal clinical
care both before and for 12 weeks after that injection when they were again assessed at
Assessment 1 (A1). These eight, together with a further seven children were block randomised
by age, gender and GMFCS level into either a PRE or POST BoNT-A strength training group.
Children completed four assessments; (A1) timed approximately 12 weeks prior to their
scheduled BoNT-A injection, Assessment 2 (A2) approximately 2 weeks prior to their scheduled
injection, Assessment 3 (A3) on average 5 weeks (SD 1week, range 3-6weeks) post injection
and Assessment 4 (A4) approximately 14 weeks post injection. The PRE strength training group
completed strength training in the weeks between A1-A2 and the POST strength training group
completed the training between A3-A4 (Figure 1). In the weeks where the children were not
allocated strength training, they continued with their normal care routine, without
participating in any new activities.
BoNT-A
Normal Care
Routine
Normal Care
Routine
Control Period n=8
W-26
W-12
BoNT-A
A2 A3
A1
B
A4
PRE strength
training
Normal Care
Routine
Normal Care
Routine
POST strength
training
W0
W12
W26
participants forming a control period, and 15 children completing the intervention period. Vertical
dashed lines represent the timing of Botulinum Neurotoxin injections.
124
6.3.2.1 ACTIVITY
6.3.2.1.1 FUNCTIONAL MOBILITY
The 6-minute Walk Test (6MWT) and the Timed-up-and-Go test (TUG) were used to measure
functional walking capacity38 and were selected as common standard assessments for clinical
assessment. For the 6MWT, the total distance walked was recorded. Children performed the
TUG assessment from an adjustable-height chair in accordance with the test protocol39 (with
the fastest of 3 trials being recorded). Both assessments were completed barefoot. Reliability
and validity of TUG has been examined in children with physical disabilities, with high levels of
test-retest reliability (ICC = 0.83), and shown to be responsive to change39, whilst the 6MWT
has been shown as a reliable test for independently ambulant children with CP40.
6.3.2.2 P ARTICIPATION
6.3.2.2.1 THE CANADIAN OCCUPATIONAL PERFORMANCE MEASURE (COPM)
The Canadian Occupational Performance Measure (COPM)41 defined individual goals by an
experienced occupational therapist. The COPM is based on an interview, which allows
individuals to identify goals, based on activities they consider important but find difficult to
perform. Goals were both activity and participation based. Participants were then required to
rate their performance, and satisfaction with that level of performance for each of their selfselected goals. Both performance and satisfaction are rated on a 1-10 numeric rating scale (1=
not able to perform at all, or not satisfied at all, 10= able to perform extremely well, or
extremely satisfied). Whilst both the child and parent were interviewed for goal setting only
the parent scores were used in the analysis. The COPM scores collected before and after the
child’s strength training period are reported.
6.3.2.2.2 THE ASSESSMENT OF LIFE HABITS, CHILD SHORT FORM (THE LIFE-H)
Participation was assessed with the Assessment of Life Habits, children short form (LIFE-H)42,
which was completed by the parent due to time constraints. The LIFE-H considers the way in
which the young person accomplishes their life habits at home, at school and in the wider
community. The LIFE-H comprises 62 items grouped into 11 domains covering both daily
activities and social roles. One question about sexual relations was omitted as it was not age
appropriate for the children in this study. The LIFE-H can be used for children with a variety of
disabilities aged between 5–13 years42. It has moderate to high intra and inter-rater reliability
(0.78 or higher for 10 out of 11 categories—interpersonal relationships scored an intra-rater
correlation coefficient of 0.58) and has been validated for children with CP42. The scoring
125
system scores participation as lower not only if the child has greater difficulty in participation
but also if more assistance is needed.
6.3.2.3 QUALITY OF LIFE
6.3.2.3.1 CEREBRAL PALSY QUALITY OF LIFE QUESTIONNAIRE FOR CHILDREN (CP QoL-CHILD)
Quality of life was measured with the parent proxy version of the Cerebral Palsy Quality of Life
Questionnaire for Children (CP QoL-Child)43, suitable for children aged 4 to 12 years. The CP
QoL-Child assesses seven domains of QoL including social well-being and acceptance, feelings
about functioning, participation, and physical health, emotional well-being, access to services,
pain and feeling about disability and family health. This tool is considered to be
psychometrically sound44, and a recent review of the QoL measures for children with CP, found
the CP QoL-Child to be one of the strongest measures of QoL in children with CP and the only
one to wholly fulfil the definitional criteria of QoL45. Both the LIFE-H and the CP-QoL
questionnaires were completed by the same parent at each assessment time point.
6.3.3 TRAINING PROGRAM
Participants completed a home based strength training programme, training three times a
week for 10 weeks (completing a minimum of 20 sessions). Programme coordination and
progression was conducted fortnightly by a visiting exercise physiologist, with the remaining
training sessions conducted by a trained family member. Each training session included manual
and passive stretching of the lower limb muscle groups. The design of the strength program
was based on the child’s initial strength assessment and the functional goals. The program
initially focused on motor control; with manual resistance and the use of a thera-band(s), then
establishing base strength with ankle weights, increasing first the number of repetitions and
then loads. During the 10 weeks of the training, the program progressed to more complex
movements and functional tasks reflecting the child’s goals (e.g. running, stepping up kerbs,
kicking a ball etc.). Participants were requested not to take up any new activities but to
maintain, and record, their usual therapy program throughout the study.
Analysis A: To estimate the effect of strength training with respect to BoNT-A injection, the
mean and 95% confidence interval of within subject change of each outcome score over the
control period (B to A1) was compared with changes for the same eight subjects over the
126
intervention period (A1 to A4). Statistical significance was assessed with a 2-tailed t-test, and
considered statistically significant if p<0.05.
Analysis B: To estimate whether the timing of the strength training was important, the mean of
within subject change of each score over the strength training period for those in the PRE
group (A1-A2) was compared with those of the POST group (A3-A4). Similarly, mean within
subject changes were also calculated over the entire intervention period for both groups (A1A4). Effect sizes were determined using Cohen’s d equation46.
6.4 RESULTS
6.4.1 ANALYSIS A: CONTROL AND INTERVENTION GROUP, INDEPENDENT OF TIMING
(N=8 CHILDREN)
6.4.1.1. ACTIVITY
6.4.1.1.1 FUNCTIONAL MOBILITY (TUG, 6MWT)
Children completing the control period had no statistically significant changes in TUG or 6MWT
over the control period (Table 1), however the same group of children were significantly faster
in performing the TUG (t(7)=2.464, p=.043, ES=0.55) after the intervention period, with an
average within subject improvement of 0.54sec (SE 0.22).
6.4.1.2.1 THE ASSESSMENT OF LIFE HABITS (THE LIFE-H)
Over the control period there was no statistical significance change in levels of participation
(Table 1). Over the intervention period, changes in levels of participation were more likely to
be positive (6 domains) than in the control period, with improvements reaching statistical
significance in the domains of nutrition (t(6)=-3.283, p=.017, ES=0.44), relationships (t(6)=2.550, p=.043, ES=1.44) and education (t(6)=-2.669, p=.037, ES=0.16), albeit with a small effect
size.
Children showed no statistically significant change in QoL over the control period. Over the
intervention period the average within subject change of 5.47 (SE 1.75) was statistically
significant with respect to QoL in family health (t(6)=-3.041, p=.023, ES=0.30). For emotional
well-being and self-esteem the average within subject change of 4.17 (SE 2.84) approached
statistical significance but with a small effect size (t(6)=-2.397, p=.053, ES=0.29).
127
Table 1 Mean within-subject change of scores for outcome measures of activity,
participation and QoL for the control and intervention period (n=8). *Significance at p<.05.
#
Approaching significance at p<.06.
ICF level
Outcome measure
Mean within subject change (SE)
Control
Intervention
TUG (sec)
0.18 (0.27)
-0.54 (0.22)*
6MWT distance (m)
10.64(14.01)
12.29 (16.44)
Nutrition
0.31 (0.22)
0.79 (0.38)*
Fitness
-0.07 (0.33)
0.60 (0.74)
Personal care
-0.07 (0.40)
0.55 (0.70)
Mobility
0.76 (0.25)
0.52 (0.39)
Responsibilities
0.38 (1.12)
-0.08 (1.19)
Relationships
-0.61 (0.27)
0.77 (0.30)*
Education
-0.46 (0.56)
0.42 (0.26)*
Recreation
-0.41(0.45)
-0.23(0.17)
Social well-being and acceptance
0.00 (1.77)
1.28 (2.01)
Functioning
-0.84 (1.14)
-0.12 (1.54)
Participation & physical health
3.98 (2.34)
-3.27 (2.39)
Emotional well being & self esteem
-3.39 (2.23)
4.17 (2.84)
Access to services
-6.45 (4.64)
5.60 (3.52)
Pain & disability
9.07 (5.75)
-0.08 (5.19)
Family health
-0.39 (3.89)
5.47 (1.75)*
Activity
Participation
(LIFE-H)
QoL
(CP-QoL)
#
6.4.2 ANALYSIS B: INTERVENTION GROUP (N=15 CHILDREN), WITH TIMING OF
TRAINING CONSIDERED.
6.4.2.1 ACTIVITY
6.4.2.1.1 FUNCTIONAL MOBILITY (TUG, 6MWT)
The PRE group had a statistically significant decrease of 0.42 sec (SE 0.13) in TUG time
following (A1-A2) 10 weeks of strength training (t(6)=3.251, p=.017, ES=0.45). The POST group
significantly decreased in TUG time by an average change of 0.62sec (SE 0.17) over 10 weeks
of strength training (A3-A4), (t(7)=3.579, p=.009, ES=0.81) (Table 2).
128
Over the 6 month intervention period (A1-A4), there was a significant decrease in TUG time for
all 15 children, with an average within subject decrease of 0.59sec (SE 0.13) (t(14)=4.623,
p<.001, ES=0.68). Both the PRE (t(6)=3.208, p=.018, ES=0.56) and POST (t(7)=3.123, p=.017,
ES=0.80) group performed the TUG significantly faster over the 6months (PRE: 0.58sec, SE
0.18, POST: 0.59sec, SE 0.19) (Table 2).
There were no significant changes made in distance covered in the 6MWT for either group
over the entire 6month intervention period (p>.05). However, over the 10weeks of strength
training, the increase in the distance covered by the PRE group approached statistical
significance, mean=46.86m, (t(6)=-2.828, p=.060, ES=0.63), and the POST group, mean=37.79m
(t(7)=-2.687, p=.031, ES=0.35) reached statistical significance (Table 2).
6.4.2.2.1 THE CANADIAN OCCUPATIONAL PERFORMANCE MEASURE (COPM)
A change of two points or more on the COPM is considered clinically significant41. A total of 16
goals were set by the children participating in the PRE group, of these, 11 (69%) had a clinically
significant improvement in the parent score for satisfaction and 13 (81%) demonstrated a
clinically significant improvement in the parents score for performance. As a group the PRE
group displayed a mean within subject change of 2.17 and 2.61 for performance and
satisfaction respectively. In the POST group a total of 15 goals were set; of these 11 (73%)
showed a clinically significant improvement in satisfaction and 8 (53%) demonstrated a
clinically significant improvement in performance. As a group, the POST group displayed a
mean change of 1.64 and 1.50 for satisfaction and performance.
The COPM scores for the entire cohort grouped together increased by 1.90 for the parent
score of satisfaction, and 2.05 for the parent score of performance.
6.4.2.2.2. THE ASSESSMENT OF LIFE HABITS (THE LIFE-H)
Neither the PRE or POST group showed significant changes in level of participation either over
10 weeks or over 6 months across the domains of the LIFE-H (p>.05). Nor were significant
changes evident for the entire cohort over the 6months of the study on the LIFE-H (Table 2).
129
Table 2 Mean within-subject changes for outcome measures of Activity, Participation and
QoL, with changes shown over the 10 weeks of strength training and 6 months.*Significance
at p<.05, #Approaching significance at p<.06.
ICF Level
Outcome measure
TUG (sec)
Activity
6MWT (m)
Nutrition
Fitness
Personal care
Mobility
Participation
(LIFE-H)
Responsibilities
Relationships
Education
Recreation
Social well-being
and acceptance
Functioning
Participation &
physical health
QoL
(CP-QoL)
Emotional well
being & self esteem
Access to services
Pain & disability
Family health
Group
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
PRE
POST
All
Initial score
(SE)
4.71 (0.38)
4.91 (0.23)
4.82 (0.21)
537.03 (31.16)
493.35 (26.32)
515.33 (20.66)
6.19 (1.12)
7.87 (0.73)
7.09 (0.67)
8.33 (0.71)
9.06 (0.27)
8.72 (0.36)
6.33 (1.03)
7.57 (0.51)
6.99 (0.56)
7.64 (0.96)
7.34 (0.87)
7.50 (0.63)
6.65 (1.21)
7.66 (0.68)
7.19 (0.66)
9.10 (0.33)
8.64 (0.70)
8.85 (0.40)
5.83 (0.99)
8.19 (0.64)
7.09 (0.64)
6.49 (1.28)
8.13 (1.11)
7.37 (0.84)
83.28 (11.06)
86.79 (4.18)
85.15 (2.63)
77.90 (4.16)
87.26 (4.66)
82.89 (3.29)
74.35 (4.72)
81.53 (4.37)
78.18 (3.24)
77.02 (3.52)
88.80 (3.92)
83.31 (3.56)
69.97 (7.58)
82.19 (2.86)
76.48 (4.04)
38.07 (8.10)
20.20 (4.09)
28.54 (4.82)
67.86 (6.71)
84.38 (4.92)
71.04 (4.61)
Change after
10weeks (SE)
-0.42 (0.13)*
-0.62 (0.17)*
#
46.86 (20.53)
37.79 (11.83)*
1.90 (0.66)
0.01 (0.49)
0.32 (0.63)
-0.56 (0.45)
0.24 (0.69)
0.00 (0.27)
0.16 (0.46)
1.43 (0.73)
-0.77 (0.83)
-0.91 (0.85)
0.52 (0.28)
-0.13 (0.08)
0.84 (0.62)
-0.32 (0.16)
0.19 (0.35)
1.02 (0.40)
2.60 (2.96)
-1.38 (2.86)
5.90 (1.67)*
-0.46 (1.49)
4.38 (3.18)
-1.58 (2.74)
4.76 (5.61)
-2.08 (2.43)
8.15 (3.07)*
-10.98 (10.91)
-7.05 (4.21)
-2.15 (3.10)
4.76 (6.13)
2.73 (3.20)
Change after
6months (SE)
-0.58 (0.18)*
-0.59 (0.19)*
-0.59 (0.13)*
32.44 (32.26)
56.09 (34.20)
45.05 (23.02)
1.98 (0.60)
0.34 (1.08)
1.16 (0.64)
0.63 (0.82)
0.16 (0.41)
0.40 (0.44)
0.66 (0.69)
-0.25 (0.53)
0.20 (0.44)
0.20 (0.16)
2.06 (0.93)
1.13 (0.52)
0.60 (1.37)
0.59 (0.77)
0.59 (0.75)
0.79 (0.31)
1.36 (0.82)
1.07 (0.43)
1.42 (0.53)
0.58 (0.40)
1.00 (0.34)
0.85 (0.55)
1.93 (1.22)
1.39 (0.66)
5.19 (2.99)
-3.41 (3.35)
0.61 (2.47)
3.83 (2.38)
-2.67 (1.39)
0.32 (1.56)
3.57 (3.56)
-1.99 (2.51)
0.61 (2.18)
9.29 (3.87)#
-1.30 (4.90)
3.64 (3.38)
0.86 (4.05)
-12.39 (9.28)
-6.20 (5.42)
-3.25 (4.70)
-0.86 (4.42)
-1.98 (3.12)
6.70 (2.20)*
16.41 (12.07)
11.88 (6.44)
130
Children in the PRE group had significant within subject increases of 5.90 (SE 1.67) in
functioning (t(6)=-3.525, p=.012, ES=0.51) and of 8.15 (SE 3.07) (t(6)=-2.655, p=.038, ES=0.41)
in access to services over the 10 weeks of strength training (A1-A2) (Table 2).
When assessed over 6 months, the PRE group showed a significant increase in score of 6.70 (SE
2.20) in family health (t(6)=-3.041, p=.023, ES=0.42) and the increase in emotional well-being
and self-esteem of 9.29 (SE 3.87), (t(6)=-2.397, p=.053, ES=0.70) approached statistical
significance. The POST group showed no significant changes in QoL over the course of the
study (p>.05) (Table 2).
As a whole, the 15 children in the intervention group showed no significant changes in within
subject changes QoL over the intervention period p>.05) (Table 2)
6.5 DISCUSSION
This study combined two commonly used treatment interventions, BoNT-A and strength
training, to target two primary motor impairments of CP; spasticity, and muscular weakness 1.
Previously published work from this project successfully demonstrated a simultaneous
decrease in spasticity and increases in muscle strength, which had associations with improved
performance in functional goals31 and gait37. However, a comprehensive treatment approach
needs to consider all levels of functioning, not just target impairments. This study found
children with CP showed some improvements in the activity, participation and QoL domains of
the ICF after treating both spasticity and muscle weakness at the impairment level.
There was no change in the TUG times for (eight) participants over the 6month control phase,
but during the intervention period there were significant improvements seen immediately
after 10 weeks (of strength training) and over 6 months. Separately, BoNT-A injections and
strength training have each been shown to result in improvements in the TUG47, 48 within the
adult population. A potential mechanism for BoNT-A could be reduced co-activation
patterns48, whilst the strength training may have increased muscle size31, 49, and improved
inter-muscle coordination50. The TUG test measures components of the ICF; including the
ability to change and maintain body position and walking51, changes in TUG scores may reflect
alterations in muscle strength. The 6MWT, which reflects functional endurance, however was
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not altered by the addition of strength training. Thus, our strength training intervention
improved coordination, maintenance of body position and walking initiation but did not affect
functional endurance capacity. Future strength training interventions perhaps should
endeavour to include components of fitness and endurance to increase walking endurance.
The LIFE-H assessment of participation in daily and social activities, demonstrated no
significant changes in participation following the combined intervention when all fifteen
children in the study were considered. However, it should be noted that for the eight children
who also participated in a control period, levels of participation were more likely to be positive
after the intervention, and were significantly improved in the domains of nutrition, education
and (most notably) relationships. Being a home based strength intervention whereby the
parents were responsible for assisting and supervising at least one (more commonly two) of
the three sessions each week, it could be suggested that the additional interaction between
the parents and the child played a role in the increases seen in the relationship domain of
participation. This was an unplanned but positive secondary outcome of the intervention
program, however this result should be viewed with caution as the ‘relationships’ category of
the LIFE-H is reported to have a lower intra–rater reliability (0.58) than other categories of the
LIFE-H. As for improvements in participation within the domains of nutrition and education,
perhaps by participating in the strength training there was an increased awareness of the
child’s capabilities or even an increased encouragement for participation in these areas from
the parent after first completing the questionnaire. These reasons are more likely to explain
perceived improvements rather than the actual intervention itself. The results from the COPM
indicated a clinically significant improvement in performance of goals as perceived by the
parent, and a trend for improvement in scores for satisfaction. The measurement of
satisfaction is possibly confounded by the parent’s expectations and their level of comparison
with the typically developing population, and there may also be an element of a ceiling effect.
Few intervention studies have looked at participation as an outcome, and those that have,
have used different measures of participation. Looking at the effect of BoNT-A alone, Bjornson
et al., (2007), reported no effect as measured by COPM satisfaction scores and the Goal
Attainment Scale52. Two studies looking at the effect of exercise programs have reported
increases in participation (as measured by a semi structured interview, and The Children’s
Assessment of Participation and Enjoyment)32, 53. Changes measured in the group completing
both control and intervention periods (n=8) agree with the exercise program literature.
However, the results of all 15 children in the study are conflicting, with no significant changes
shown over the intervention period. This may be a chance effect due to the small sample size.
Or perhaps the parents of the control-intervention group perceived better results after being
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involved in the study for longer period before receiving strength training. Research with larger
sample sizes would be beneficial in producing greater statistical power and confidence in
interpreting changes. A limitation of this study was the use of the LIFE-H instrument to
measure participation as it does not capture frequency of participation; a measure including
frequency would have provided greater detail and may be more sensitive to change. This study
supports the inclusion of a participation measurement for intervention outcome; however it
also highlights the need for more precise measures of participation in the CP population.
As with participation, there is little research pertaining to the effect of either BoNT-A or
strength training on QoL. Whilst one study found no effect of BoNT-A injections on QoL54
(using the Pediatric Quality of Life Inventory), a number of studies have indicated a positive
impact of strength training on QoL in children with CP36, 53,55 (as measured by the Pediatric
Quality of Life Inventory, the Children’s Health-Related Quality of Life, the Pediatric Outcomes
Data Collection Instrument and the Child Caregiver Questionnaire). That being said, these
results are difficult to compare with the present study as different measures of QoL were used,
and were not condition specific. Tsoi et al., (2012)56 suggested that if improvements in QoL are
to be expected in the management of CP, there is a need for comprehensive treatment
approaches. In this study, QoL improvements were indicated in domains of family health, and
emotional well-being and self esteem after the intervention that were not seen in the control
period. The increase in time that the child and parent spent together, as necessitated by the
nature of the intervention, may be accountable for the improved QoL for family health and
perhaps even in the improved emotional well-being and self esteem. The latter may also be
attributed to the positive changes occurring at the level of impairment, possibly leading to
improvements in functional ability. This is an especially interesting outcome, with previous
research reporting children with CP experience a lower QoL across all domains, in particular
physical and emotional wellbeing3, 4. Whilst this study did not result in improvements in the
participation and physical health domains of the CP-QoL, the intervention implemented in this
study was targeted at the impairment level, and not at participation or QoL. Whilst we do
report (limited) positive effects on participation and QoL, future research should investigate
implementing additional interventions directly targeting the participation and QoL. A limitation
of this study was that the children themselves did not complete the CP-QoL, LIFE-H or score
the COPM. However, lengthy questionnaires were inappropriate for children as young as five.
Despite these limitations, these results are positive, and demonstrate potential for combining
treatment modalities for improving participation and QoL for children with CP.
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The majority of outcome measures did not differ by the timing of strength training with
respect to BoNT-A. The exceptions were the perceived level of performance of and satisfaction
with clinical goals, as assessed by the COPM, and the domains of family health and emotional
well-being and self esteem from the CP-QoL, which all favoured the PRE group. In contrast to
the PRE group, the POST group did not show any clinical improvements in either satisfaction or
performance with defined COPM goals over the strength training period. The assessment of
the COPM after BoNT-A for the POST group, may have modified parental perception; the
parents scored the child higher to begin with because they felt the BoNT-A was in effect
(therefore there was less room for improvement for these children). In terms of the PRE
group’s superior performance in the CP-QoL, it is suggested that participating in strength
training prior to the injection of BoNT-A allowed the participants parents’ more time for
reflection of the changes made from the intervention, comparative to the POST group. A
follow up assessment may have confirmed or refuted this reasoning.
The results of this study are limited by our small sample size, and it should be noted that this
study included a group of highly motivated and proactive families; to enrol in such an
extensive study in the first place is reflective of this. It is likely that within such a family,
outcomes such as participation may already be higher than in children of those families who
declined involvement in this study. Comparisons of our sample of CP children to typically
developing (TD) children were not formally performed, however previous research in a similar
population of children with CP (GMFCS I-II) has reported this, and found children with CP to
generally experience lower QoL in domains such as social well-being and acceptance,
emotional wellbeing and self esteem and family health, and were statistically lower with
respect to functioning and participation and physical health15. This was similar to levels of
participation, with generally lower levels of participation compared to a TD population across
most domains of the LIFE-H15. This tells us that relatively high functioning children with CP (as
reflected by their GMFCS level) still require attention for improvements in these aspects of
functioning.
6.6 CONCLUSION
The combination of BoNT-A and strength training provided a comprehensive treatment
targeting two key impairments of CP. This study made a holistic investigation of the impact of
combined interventions on the activity, participation and QoL domains of the ICF. A positive
effect on activity, as assessed by the TUG was observed, however no effect was observed on
the 6MWT. Some improvements were observed in participation, measured by the LIFE-H, in
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the areas of nutrition, education and relationships, whilst QoL improved in the areas of family
health and emotional well-being and self esteem (assessed by the CP-QoL). The COPM
indicated a clinically significant improvement in performance of functional goals. It is
suggested that these positive results are a consequence of both reducing impairments
(spasticity and muscle weakness), and increasing the time the parent spent with their child.
This study supports the use of a multidimensional assessment of treatment interventions.
Future research should continue to develop more effective measurement outcomes
particularly for participation, and endeavour to consider assessments at all levels of the ICF to
determine optimal treatment planning.
This project was supported by Princess Margaret Hospital (PMH) Foundation Grant. The
authors would like to thank the Department of Paediatric Rehabilitation, PMH for their support
and assistance with recruitment. Authors would also like to acknowledge the contribution of
the School of Sport Science, Exercise & Health at UWA for the use of equipment and facilities.
Sincere thanks go to the children and families who volunteered to participate in this study.
135
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139
CHAPTER SEVEN
SYNTHESIS OF RESULTS AND CONCLUSION
7.1 SUMMARY
Cerebral Palsy (CP) is one of the most common childhood physical disabilities in the world1.
With no known cure, the aim of many current treatment modalities is to manage outward
expressions of the disorder2. For most children with CP, the associated motor impairments
affect many aspects of the child’s life, and many different management strategies are
required. Spasticity and muscular weakness are two major motor impairments associated with
CP3, both receiving substantial attention throughout the literature. Botulinum Neurotoxin
Type-A (BoNT-A) is a commonly used treatment for spasticity management, whilst strength
training is shown to be an effective therapeutic option for targeting muscle weakness4-8. Whilst
a number of studies have advocated a multifaceted approach to spasticity reduction and
specific muscle strengthening in the management of children with CP9, 10, apart from one
recent pilot study11, no research has formally combined BoNT-A therapy and strength training
in multiple muscles of the lower limb in children with CP.
The International Classification of Functioning Disability and Health (ICF)12 is a theoretical
classification framework, devised by the World Health Organisation, that incorporates all
aspects of functioning, and captures the breadth of difficulties experienced by those with CP13.
The ICF promotes a broad application of outcome measures to ensure interventions and
rehabilitation programs are being evaluated, not only at the level of the organ system
(impairments), but also at the individual (activity limitations) and societal levels (participation
restrictions)14. Therefore to provide a comprehensive evaluation of the combination of lower
limb strength training in children with CP receiving BoNT-A injections, the use of the ICF is of
great relevance. Therefore this research aimed to evaluate the effects at all levels of the ICF of
a home based, goal directed, and individualised strength training program combined with
BoNT-A injections for spasticity management for children with CP. Specific outcome measures
include muscle strength, spasticity, muscle morphology, gait, activity, participation, quality of
life, and the attainment of functional goals. A secondary aim of this study was to determine
the best practice in terms of timing of a strength training intervention in relation to reception
of BoNT-A for children with CP. Specifically to establish whether outcomes are most improved
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if training is undertaken in the weeks preceding the BoNT-A injection, or in the weeks after the
injection.
The research questions outlined above were addressed using four interrelated studies. This
chapter will summarise the findings of each of these studies with respect to the hypotheses
developed in Chapter One, draw conclusions based on the results of each of these studies, and
make recommendations for clinical implications and future research.
7.1.1 CHAPTER THREE
MORPHOLOGICAL ALTERATIONS IN SPASTIC MUSCLES IMMEDIATELY FOLLOWING
BOTULINUM NEUROTOXIN TYPE-A TREATMENT IN CHILDREN WITH CEREBRAL PALSY.
Children with CP have a good functional response following BoNT-A treatment15-17, however
there is evidence for an atrophic effect of BoNT-A documented in typically developing muscles
in human18 and animal19, 20 research. To the authors’ knowledge, this change in muscle size has
not yet been investigated in pathological muscles. Chapter Three aimed to provide the first
known documentation of the morphologic alterations of spastic muscles in response to BoNTA. To report the comprehensive effect of the neurotoxin, we also aimed to investigate the
morphologic response in synergist and antagonist muscle to BoNT-A treatment in spastic
muscle, and finally, we aimed to increase understanding of the effect of BoNT-A treatment on
muscle strength in children with CP.
The first hypothesis that;
‘Muscles injected with BoNT-A will undergo a reduction in muscle volume’
is supported. The injected gastrocnemius muscles showed an average of 4.5% atrophy, a
statistically significant decrease in the 15 children in the study. For five children receiving
BoNT-A into the medial hamstrings, there was an average decrease of 5.9% in muscle volume,
however this did not reach statistical significance. Interestingly, the synergist for the
gastrocnemius muscle, the soleus, displayed statistically significant increase in muscle volume
of almost 4%, which appeared to compensate for the atrophy of the gastrocnemius, to result
in no change in the entire plantar flexor muscle group volume (the sum of the gastrocnemius
and soleus muscle volume). There was no change in muscle size of the antagonist muscles.
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The second hypothesis that;
‘BoNT-A induced muscle atrophy would also result in a reduced force generating capacity’
was partially supported. Measures of gastrocnemius atrophy were not concurrent with a
reduction in our measure of plantar flexor muscle strength, however i) as already stated,
whole plantar flexor muscle volume did not change, and ii) the use of the hand-held
dynamometer to measure for plantar flexor strength may have provided insufficiently reliable
results. Isokinetic knee flexor strength did demonstrate a significant reduction in torque
generation, it is suggested that this may have been a result of the gastrocnemius contribution
in knee flexion, which would in fact support our hypothesis. In the group of five children who
had both the gastrocnemius and medial hamstring muscle targeted for injection, there were
decreases in torque generation; however the decrease was not sufficiently large to attain
statistical significance.
To the knowledge of the authors, this was the first study to report upon the immediate
morphological, and strength alterations in spastic muscles following BoNT-A treatment. The
atrophy measured in our sample of children with CP was not as large as that reported in
animal and healthy muscle research. However it must be noted that this was not the muscles
first response to BoNT-A, as children had already received a minimum of two series of BoNT-A
prior to the study. Whilst strength deficits were not seen following a single site injection in this
study, and there were no detrimental effects on the children’s functional performance,
attention should be paid to muscle alterations of children undergoing treatment to several
sites on multiple occasions.
7.1.2 CHAPTER FOUR
INTERVENTION IN CHILDREN WITH CEREBRAL PALSY: THE IMPACT ON MUSCLE
MORPHOLOGY AND STRENGTH.
Consistent evidence has demonstrated reduced muscle volume in affected muscles for
children with CP21, potentially influencing the ability of muscle to generate torque22 and
power21. Strength training in the CP population is shown to be a successful intervention for
muscular weakness4-8, and may also increase muscle size23. With both muscular weakness and
spasticity considered to be significantly detrimental to function in children with CP24, it seems
logical to administer strength training concurrently with BoNT-A treatment to further improve
clinical outcome for patients.
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Chapter Four aimed to combine a 10 week, home based, strength training program with BoNTA injections and measure the effects on muscular weakness and spasticity in CP. The papers’
primary aim was to determine if the combined interventions would be more successful in
improving muscle strength than BoNT-A and normal care. Secondly, this paper aimed to
determine if changes in muscle strength could be attributed to alterations in muscle
morphology. And thirdly, to report if the combination of therapies would successfully improve
individual functional goals set by the children (with parental assistance) in this study. Clinical
funding structures, family life, and other treatment plans all inhibit year-round strength
interventions, therefore it is also of importance to determine if the timing of strength training,
whether it be administered before or after BoNT-A injections, affects outcome.
‘The combination of strength training and BoNT-A will result in the simultaneous increase of
muscle strength and reduction in muscle spasticity’
was supported. The results demonstrated a significant reduction in spasticity scores, with
significant increases in our measures of muscle strength of the knee flexors and extensors, and
the gastrocnemius and tibialis anterior. However, the strength improvements are tempered by
some strength gains also indicated by children over the control period (BoNT-A with standard
clinical care). This may be in part due to normal growth, but it is also common that strength
training of some form is incorporated as part of a child’s standard clinical care.
‘The 10 week strength intervention will evoke increases in the muscle size of targeted muscles’
was partially supported. Significant increases in muscle volume were shown in all assessed
muscle groups (including those injected by BoNT-A), measured directly over the 10 weeks of
strength training, and over 6 months including BoNT-A injections. However, increases in
hamstring, quadriceps and plantar flexor volume were also measured in the control period,
and were not dissimilar to changes measured over the intervention period. Again, the change
in the control period may be attributable to normal growth and to uncontrolled activities as
part of the children’s standard clinical care.
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The third hypothesis that;
‘The combined intervention program, including individual goal-directed strength exercises, will
result in functional goal-attainment, as measured by the Goal Attainment Scale (GAS).’
was supported. Scores from the GAS demonstrate that over the 6months of the study, with the
combination of BoNT-A and strength training, children were able to achieve their functional
goals, with all children achieving a statistically significantly increase in their GAS score.
However, these results are limited by a lack of direct control data.
The final hypothesis that;
‘Children undertaking strength training in the weeks after BoNT-A treatment will have better
outcomes of muscle strength, morphology and functional goals than those receiving strength
training before BoNT-A treatment’
was not supported. The overall outcomes (6months) did not indicate any significant
differences in muscle strength between the PRE (training prior to BoNT-A) or the POST
(training after BoNT-A) groups. However, the results did reveal an emerging trend; in the
immediate (10week) response to strength training, the POST group consistently displayed
greater increases in strength, having the most significant increases across the assessed
muscles, whilst the PRE group displayed greater changes at 6months.
The outcomes from this paper report the combination of a home based strength training
program, applied either before or after BoNT-A injections, to be successful in improving
muscular strength, decreasing spasticity and in achieving functional goal attainment for
children with CP. What makes this study novel, and particularly pertinent to the CP population,
is that it has demonstrated these positive changes simultaneously in the lower limb, by
combining the use of these two common therapies targeting two major motor impairments for
children with CP. This is one of the first studies to purposefully apply strength training in
conjunction with the best practice of BoNT-A therapy, making these findings even more
relevant for clinical decision making. With recent publications of two separate pilot studies
pertaining to this topic this year25, 11, it is evident that this direction of research has potential
for future therapy for the CP population. Elvrum and Colleagues (2012)25 investigated the
combination of resistance training and BoNT-A in the hand25, whilst Bandholm and Colleagues
(2012)11 included progressive resistance training in their physical rehabilitation program
following BoNT-A treatment of the ankle plantar flexors11. Both studies reported positive
144
outcomes of strength training, with the latter also indicating trends of improvements in
function11 and the former concluding that more task-related resistance training may be
required25.
In the present study, the strength training was a home based program, centred on each child’s
individually set goals, and focused on multiple muscles of the lower limb. Whilst improvements
were seen in all of muscles targeted for training, of distinct interest were the increases
measured in the gastrocnemius and the knee flexor strength after the strength training
(comparative to the control period). This is of particular importance, as the gastrocnemius and
the hamstring muscles are frequently targeted for BoNT-A injection in this group of children.
Given the positive strength increases in the injected muscles following training, and
corresponding increases in morphology, the results suggest that perhaps future strength
training should be targeting the injected muscles.
Finally, this study also questioned the timing of strength training, whether it be more effective
if administered before or after BoNT-A injection. There appeared to be no distinction in the
timing of the strength training, however PRE training may be more suitable for a child
scheduled to receive other interventions following BoNT-A (i.e. serial casting) as they had the
better longer term outcomes, whereas, POST BoNT-A training may be more appropriate in
order to achieve immediate results for functional goals for some children. This study supports
the future application of combined BoNT-A treatment with strength training for children with
spastic CP. As a home based, individualised and goal directed strength program, it also
provides clinically relevant evidence that should be considered as a potential treatment
direction, and transitioned into clinical care.
7.1.3 CHAPTER FIVE
IMPROVING THE GAIT OF CHILDREN WITH CEREBRAL PALSY USING THE COMBINED
INTERVENTIONS OF STRENGTH TRAINING AND BOTULINUM NEUROTOXIN TYPE-A.
Commonly targeted in therapeutic goals26, inefficient ambulation, is one of the most significant
functional limitations of CP27. Muscular weakness is considered to be directly related to gross
motor function and gait24,
28
in children with CP, and strengthening programs have
demonstrated improvement in gait kinematics29-32. Lower limb muscle strength has been
linked with gait patterns in CP gait28, particularly in kinetic variables at the ankle. Yet, there
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have been minimal investigations into alterations in joint power in gait following
strengthening, and of the limited studies available, results have been inconclusive31.
Separately, BoNT-A treatment and strength training both appear to have a positive impact on
gait in children with CP, therefore it could be assumed that the combination of the therapies
would also further improve gait function. The primary aim of this paper was to measure the
effects of combining a 10 week, home based, strength training program with BoNT-A injections
in CP on walking gait, evaluated with the Gait Deviation Index (GDI) and kinetic power profiles.
The decision to include the GDI was made to provide a global measure of the kinematic
variables of gait, rather than reporting on a multitude of variables. A secondary aim of this
paper was to determine if the timing of strength training, affects outcomes, thereby indicating
whether there is an optimal timing of strength training. Finally, with this information this paper
aimed to provide guidelines for further rehabilitation planning to enhance therapy outcomes
for children with CP.
The hypothesis that;
‘The combination of strength training and BoNT-A will improve measures of the GDI.’
was supported. Following the combination of therapies, children in our study demonstrated a
significant increase in GDI. In contrast, the children in the control period showed no significant
change in GDI.
The secondary hypothesis that;
‘The 10 week strength intervention will improve kinetic power profiles at the hip, knee and
ankle joints so that they more closely resemble those of typically developing peers.’
was partially supported. In terms of power generation, peak values significantly decreased at
the hip and knee joint to below the average calculated for our typically developing sample of
children. This is in contrast to the significant increases measured in power generation at the
hip, knee and ankle joints over the control period. Over the intervention period, power
absorption also significantly decreased at the hip joint, to levels below the typically developing
average, whilst power absorption at the knee joint also significantly decreased, to a level closer
matching, yet still higher, than the typically developing average. This may have an effect on
protecting the joint from long term injury and pain. No changes in power generation or
absorption were measured at the ankle joint. This was not altogether unexpected however, as
146
the muscles around the ankle joint were not targeted in the strength training as commonly as
other muscles, such as those around the hip and knee joints.
The last hypothesis that;
‘Children undertaking strength training after BoNT-A treatment will have better GDI outcomes
than children undertaking strength training in the weeks preceding BoNT-A treatment’
was supported. Whilst both the PRE and POST group achieved significant increases in the GDI,
children in the POST group demonstrated a greater increase in GDI.
The results from this paper demonstrate positive changes in gait profiles and kinetics from the
combination of strength training and BoNT-A injections compared with BoNT-A alone. The GDI
indicated children with CP to be walking in a style closer matching the non-pathological
population following the intervention; this is in contrast with the children in the control group,
demonstrating no change in GDI. The fact that the children in this study were already walking
at a relatively high functional level prior to the intervention (a GDI of 79), and were still able to
achieve an improvement from the combined therapies is positive, highlighting the possibilities
for interventions in higher functioning children with CP.
Previous research has linked muscle strength and kinetics in the CP population, with a focus on
the ankle at toe-off (power generation)28. This study showed the combination of lower limb
strength training with BoNT-A treatment to alter joint power outputs at the hip and knee. In
contrast to increasing trends over the control period, levels of power generated at the hip joint
decreased over the intervention, as did levels of power absorption at the knee joint, to levels
more closely matching the TD population. It is suggested that these results indicate an
improved efficiency; that the combination of strength training and BoNT-A facilitated a more
efficient power transfer through the muscles of the lower limb.
Similar to Chapter Four, this paper also endeavoured to determine the more effective timing of
strength training in relation to the BoNT-A injection: Neither group showed any distinction in
the kinetic measures of power at the hip, knee or ankle, and both groups showed significant
increases in the GDI. However the POST group, training with BoNT-A active in their system,
appeared to show the greatest improvements in GDI. With this, it is recommended to clinicians
147
to endeavour to apply strength training after BoNT-A injections, however, it does not appear
to be a critical difference.
7.1.4 CHAPTER SIX
THE COMBINATION OF STRENGTH TRAINING AND BOTULINUM NEUROTOXIN TYPE-A
IN CHILDREN WITH CEREBRAL PALSY: THE EFFECT ON ACTIVITY, PARTICIPATION AND
QUALITY OF LIFE.
The International Classification of Functioning, Disability and Health (ICF) framework33 allows
for a holistic approach to evaluating current and future treatment options. Understanding the
impact of therapeutic interventions on all dimensions of the ICF is imperative for determining
the optimal management of the impairments associated with CP. Chapter Six completes the
evaluation of the combination effects of strength training and BoNT-A therapy, by evaluating
the effect on activity, participation and QoL.
Children with CP are reported to experience greater activity limitations and are less physically
active then their typically developing peers34-36. In addition to this, literature has reported
children with CP to report difficulties in participation37-40, and to experience a lower QoL than
children who are typically developing35,
40-42
across all domains, in particular physical and
emotional well-being41, 42.
Very little research has investigated the effect of BoNT-A on activity, participation or QoL in
children with CP. Those that have, demonstrated improvements in some measures of activity43,
44
, indicated a possible positive effect on QoL45 (however with mixed results46, 47), but have not
reported an effect on participation48, 49. Similarly, few studies have included effects of strength
training in this area; literature has demonstrated a positive impact of strength training on
QoL31,
49
, with some examples of improved participation48,
50
, and little support for
improvements in activity8, 51,. The combination of therapies has not been evaluated from this
perspective. Therefore, this paper aimed to determine if a combined 10 week, home based,
strength training program with BoNT-A injections can evoke changes at the activity,
participation or QoL domains of the ICF, compared with BoNT-A injections and normal care.
Similar to the previous two papers, this paper also aimed to determine if the timing of the
strength training program, administered around scheduled BoNT-A injections would produce
different outcomes on the activity, participation and QoL domains of the ICF.
148
‘The combined interventions will improve measures of activity, as assessed by the Timed Up
and Go (TUG) and the Six-Minute Walk Test (6MWT)’
was partially supported. Results from the TUG support this hypothesis; with a statistically
significant improvement over the intervention period, whilst there was no change over the
control period. The 6MWT, however was not altered by the addition of strength training with
BoNT-A. It is reasoned that the 6MWT reflects functional endurance, whereas the TUG moreso reflects changes made in strength.
‘Children with CP will have improved outcomes of participation following their involvement in
the study (as assessed by the Assessment of Life-Habits, the LIFE-H, for children, and the
Canadian Occupational Performance Measure, COPM).’
was not completely supported. There were no significant changes in participation following the
combined interventions when the entire cohort (n=15) was evaluated. However, the control
group of children (n=8), reported significant improvements after completing the intervention
in the LIFE-H domains of nutrition, education and relationships. In addition to this, for the
entire cohort, the COPM indicated a clinically significant improvement in the parent score for
performance of goals, but not for satisfaction.
The final hypothesis that;
‘Children with CP will have improved outcomes of QoL following their involvement in the study
(as assessed by the Cerebral Palsy Quality of Life Questionnaire for Children, CP QOL)’
was supported. The domains of family health and emotional well–being/self-esteem of the CPQoL showed improvements after the intervention period that was not measured in the control
period.
This paper completed a holistic evaluation of the impact of combined interventions on the
activity, participation and QoL domains of the ICF. A positive effect on activity, as assessed by
the TUG was observed, however there was no effect on the 6MWT. Some improvements were
observed in participation, measured by the LIFE-H, in the domains of nutrition, education and
relationships, whilst QoL improved in the areas of family health and emotional well-being and
149
self-esteem. The increase in time that the child and parent spent together, as necessitated by
the nature of the intervention, may be accountable for the improved QoL for family health and
perhaps even in the improved emotional well-being and self-esteem, as well as the improved
‘relationship’ domain in participation. The COPM indicated a clinically significant improvement
in performance of functional goals. It is suggested that these positive results are a
consequence of both reducing impairments (spasticity and muscle weakness), and increasing
the time the parent spent with their child.
7.2 CONCLUSIONS
This thesis has, for the first time, provided an in depth investigation into the immediate
morphological responses to BoNT-A injections of muscles of the lower limbs in children with
CP. This confirmed our hypothesis that BoNT-A therapy would lead to atrophy of injected
muscles in children with CP, however the degree of atrophy, and concomitant reductions in
muscle strength were not as large as the literature has suggested may occur. It is likely that the
multiple number of BoNT-A injections our participants had received prior to this study may
have been a mediating factor for the small changes measured. Despite this, with the
knowledge that children with spastic diplegic CP i) experience spasticity3 ii) are typically
weaker9, (iii) have smaller muscles21 than their typically developing peers and that iv) both
spasticity and muscular weakness are reported as significant motor impairments effecting
function52-55, the new information presented in this thesis is particularly pertinent to the future
application and research of BoNT-A. Whilst the results of this study are optimistic for the
continued future of BoNT-A use, essential research investigating the response of naive muscles
to initial BoNT-A injections is needed.
Combined, these studies have also been the first study to investigate the comprehensive effect
of the combined therapies of BoNT-A and strength training across all levels of the ICF in
children with CP. With this, it is also the first to question the timing of strength training in
relation to BoNT-A injection.
Irrespective of timing, the combination of BoNT-A injections, and a home based, goal directed
strength training program was effective in increasing muscular strength that was simultaneous
to spasticity reduction. Concurrent with the increases in muscle strength were increases in
muscle volume, however it should be noted that children in the control period also displayed
150
increases in measures of muscle strength and muscle volumes for some of the muscle groups.
Functional improvements were shown over the intervention (BoNT-A and strength training)
period, with clinically significant improvements in the attainment of functional goals (GAS),
and with significant improvements in walking gait. Using the GDI, children with CP were shown
to significantly improve patterns of walking gait, walking in a pattern resembling nonpathological gait after the intervention. This outcome was further supported by the lack of
change in GDI by children over the control period. Kinetic (power) gait profiles demonstrated
that this improved walking gait was achieved with reduced power profiles at the hip and knee,
resembling that of the TD population. These results may be indicative of improved efficiency of
the muscles, and may also implicate a reduced risk of joint injury and pain in the long term and
in the adult CP population. With improvements demonstrated across the level of body
structures and function, the combination of BoNT-A and strength training also indicated some
improvements in activity and participation measures; the TUG demonstrated significant
improvements, however, the 6MWT, more a measure of functional endurance rather than
muscular strength, was not affected. Participation, as measured from the parents’ perspective
(using the LIFE-H), was shown to improve in domains of nutrition, education and relationships,
whilst the results from the COPM indicated a clinically significant improvement in performance
of goals as perceived by the parent, and a trend for improvement in scores for satisfaction. The
combination of therapies also evoked improvements in the parents perception of their child’s
QoL in the domains of family health and emotional well-being and self-esteem. From these
results, it can be concluded, and recommended to clinicians, that strength training, targeting
muscular weakness, be applied simultaneously with BoNT-A therapy for spasticity
management to improve outcomes for patients across all levels of the ICF.
With regards to the most effective timing of strength training in relation to BoNT-A injections,
neither training PRE or POST can be definitively stated as the preferred time. The PRE training
group generally displayed superior results in the perceived level of performance of and
satisfaction with clinical goals, as assessed by the COPM, and the domains of family health and
emotional well-being and self-esteem from the CP QoL. The PRE training option also appeared
to result in greater changes in measures of strength when assessed over the 6month
intervention. However, in terms of improving muscle strength over the 10weeks of strength
training, what is referred to in Chapter Four as the ‘immediate’ response to strength training,
the POST training option consistently displayed a greater capacity for changes of strength,
having the most significant increases across the assessed muscle groups. POST training also
appeared to result in larger improvements on the GDI. It appears that applying strength
151
training either before or after BoNT-A can positively impact a child with CP at all levels of the
ICF. It is up to the clinician, parents and child to individually determine the more appropriate
timing for them depending on their individual situations, until further research can confirm
otherwise.
7.2.1 FUTURE RESEARCH
In regards to the effect of BoNT-A on muscle morphology, muscular strength and function, it is
highly recommended that further research investigate the response of spastic muscles to the
first (and subsequent) series of BoNT-A. Ideally, muscles should be assessed prior to having
received any BoNT-A, providing a baseline measure, that could be referred to over each
subsequent injection of BoNT-A. Furthermore, measurements should be taken at differential
timing of the BoNT-A’s effect; this study assessed the muscles response at a time
corresponding with the BoNT-A’s peak effect, future longitudinal research would follow this
with repeat assessments over time as the effect of the BoNT-A wears off.
Based on the positive results of this thesis, the combination of strength training and BoNT-A
needs to be translated into standard clinical care; it is strongly recommended that further
research with larger sample sizes are conducted. This can provide further evidence for funding
for clinic services to include strength training for children with CP who are receiving BoNT-A for
spasticity management. This study has shown that strength training can be applied around
BoNT-A injections, as suitable for each individual circumstance. In terms of future research into
combining strength training and BoNT-A, an obvious recommendation would be to conduct
this study with a larger sample size. This could potentially allow for a randomised controlled
study with three control groups; BoNT-A with normal care, strength training with normal care,
and a no-intervention normal care group (however these groups would likely involve ethical
implications). The effects of each control group could be compared with the combination of
strength training (either PRE or POST) to provide a more thorough understanding on how each
intervention is impacting on each aspects of the child’s function. Following up with further
assessments (i.e. of at least 6 months after) would provide a better idea of changes in areas
such as participation and QoL, whereby the timeframe in this study is likely to have been too
short to look at changes in these areas. With changes predominantly seen at the level of
impairment and activity from this study, it would be interesting to also implement an aspect of
participation into the intervention program, in an aim to evoke greater changes in
participation. For example, the functional goals targeted throughout the program should then
152
be applied at the end of the program into a form of participation, whereby the child is assisted
with the development of their functional goals into the community.
We strongly recommend future research to include outcome measures across all levels of the
ICF, however in doing so, to carefully select appropriate measures. For a childhood population,
and one such as CP, finding the right selection of measures is a challenging one, we encourage
researchers to strive to determine more effective measures that can be used in this
population, in particular for measures of muscle strength and activity. It would also be useful
to investigate the economical benefit of a home based strength program around BoNT-A; if an
affordable and effective option of therapeutic intervention can be offered, perhaps more
families will have the opportunity to implement the program. Expanding the program to
include an investigation of the associated short term and long term health economics may also
provide stronger support for this intervention. Based on the results of this study, with evidence
of atrophy of injected muscles and indications of synergist hypertrophy, we suggest that future
research and clinical practice consider targeting muscles that have been injected with BoNT-A
into strength training programs, which may result in greater benefits of strengthening.
7.2.2 SIGNIFICANCE OF THIS RESEARCH
CP management is a lifelong challenge that requires a coordinated approach to treat the
impairments affecting the child holistically, involving both clinicians and the child’s family.
Treating spasticity and muscular weakness simultaneously is an obvious step in the right
direction for children with CP. This research has outlined the efficacy of implementing a home
based, goal directed strength training program for children with CP receiving BoNT-A injections
for spasticity management. Positive outcomes were achieved across numerous levels of
functioning, over and above BoNT-A alone (with standard clinical care). By including an
evaluation of the timing of strength training, this research indicated that significant
improvements in different dimensions of function could be achieved whether the training be
applied before or after BoNT-A injections. These findings have the potential to greatly impact
the prescription of strength training in combination with BoNT-A therapy in children with CP,
not only supporting its application, but also providing clinicians, and families, with an optional
time in treatment application. For example, a child scheduled to receive serial casting after
BoNT-A, now has the option to undertake strength training prior to their scheduled injection.
In CP, management in the childhood population not only involves the clinician and the child,
but also involves the family. Allowing more options for effective treatment can only serve to
153
increase the number of families able to be included in the future. Furthermore, the potential
affordability of this program also supplements this suggestion.
A limitation, and strength, of this study is how closely it matches clinical reality. The fact that a
home based strength training program, with sessions predominantly supervised by the
parents, and relatively basic equipment, is shown to successfully improve a children’s function
across all levels of the ICF is incredibly promising for the future therapy for children with CP. In
addition to this, it also demonstrates how important the role a family can play in their child’s
therapy. The real significance of this research is clearly portrayed by the children and parents
who made some impacting statements in their post strength training interviews;
“We could see progress/strengthening as the program went on – it was good for
confidence, and desire to do more! We would definitely recommend”.
Another parent stated;
“It’s been great, he has definitely benefited from the program, other people have
noticed that he must have been doing something different. He played a full game
of Rugby, on a full sized pitch; at the beginning of the program he would never
have done that. There is natural getting stronger with age, but this has brought
him to another level. He could see some tangible benefits.”
Whilst one of the children commented;
“It really showed in the sports carnival when I came a higher place than usual; I came
fifth... I usually get last.”
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APPENDICES
APPENDIX A- PUBLISHED MANUSCRIPT
A COMPARISON OF ACTIVITY, PARTICIPATION AND QUALITY OF LIFE IN CHILDREN WITH AND
WITHOUT SPASTIC DIPLEGIA CEREBRAL PALSY.
159
160
161
162
163
164
APPENDIX B- ACCEPTED ABSTRACTS
Presented at the American Academy of Cerebral Palsy and Developmental. AACPDM 66th
Annual Meeting. 2012, Toronto, ON, Canada.
Combining Strength Training and Botulinum Neurotoxin intervention in children with
CP: The impact on Muscle Morphology and Strength.
S WilliamsA, C ElliottB, J ValentineB,C, A GubbayC, P ShipmanD, S ReidA.
A
School of Sport Science, Exercise & Health, The University of Western Australia, Perth,
Australia.
B
School of Paediatrics and Child Health, The University of Western Australia, Perth, Australia.
C
Department of Paediatric Rehabilitation, Princess Margaret Hospital, Perth, Australia.
D
Department of Diagnostic Imaging, Princess Margaret Hospital, Perth, Australia.
Background/Objectives: Spasticity and weakness are significant impairments for children with
Cerebral Palsy (CP). Strength training is an effective intervention for improving muscular
strength, whilst Botulinum Toxin Type-A (BoNT-A) is an established treatment for spasticity
management. This study investigated combined effects of strength training and BoNT-A on
strength and muscle morphology in children with CP.
Study Design: A repeated measures cross-comparison randomised trial.
Study Participants: 15 children with CP receiving BoNT-A for spasticity management. Children
were classified as Spastic Diplegic, GMFCS I-II, & aged 5-12 years (m=8.52, SD 1.59).
Study setting: Tertiary paediatric hospital.
Materials/Methods: Spasticity was assessed using the Modified Ashworth Scale. The Goal
Attainment Scale (GAS) assessed achievement of functional goals. Muscle volume (MV) was
assessed using Magnetic Resonance Imaging (1.5T Sonata, Siemens). Lower limb muscle
strength was assessed using instrumented (Biodex Medical Systems) and hand held (Lafayette
Instrument Company) dynamometry.
Children were randomly allocated to 10weeks of home based lower limb strength training
either before (PRE) or after (POST) receipt of BoNT-A, children completed 3 supervised
sessions weekly. Strength training was progressive, initially focussing on motor control and
base strength, through to complex movements and functional goals. Eight children also
165
completed a 6month control period of BoNT-A without strength training. All children were
assessed four times over 6months. T-Tests and a mixed model ANOVA determined significant
differences between assessment points and groups.
Results: During the intervention period children made significant strength gains (mean p=.02,
ES=.58) compared to the control period (mean p=.22, ES=.46). Significant strength
improvements were seen immediately (e.g. mean gluteus: p=.011, ES=.83), and over 6months
(mean gluteus: p=.009, ES=.71) for both groups, but did not differ significantly between groups
(p=0.795). The POST group showed greater immediate strength gains, whilst the PRE group
incurred greater strength gains over 6months.
MV significantly increased in assessed muscle groups immediately after training (mean p<.001,
mean ES =.58) and over 6months (mean p<.001, mean ES=.60) for both groups. Both training
groups showed significant improvements in GAS scores immediately after training (mean
p=.007, ES=4.17) and over 6months (mean p=.029, ES=.99), GAS outcome did not differ
significantly between groups (p=0.35). Spasticity significantly reduced following BoNT-A
(p=.011, ES=-1.17).
Conclusions/Significance: The simultaneous use of BoNT-A and strength training was
successful in spasticity reduction, improving strength, and achieving functional goals for
children with CP, over and above treatment with BoNT-A alone. Adaptations in MV suggest
that the strength gains may be attributable to hypertrophy. The results suggest that strength
training after BoNT-A may enhance immediate muscle strength, however children who receive
PRE BONT-A training may have better long-term improvements in strength.
166
Presented at the Australasian Academy of Cerebral Palsy and Developmental. AusACPDM 6th
Biannual conference. 2012 Brisbane, QLD, Australia
Strength Training Results in Stronger but not necessarily bigger Muscles for Children
with Cerebral Palsy.
S WilliamsA, C ElliottC, J ValentineB, N SmithB, T ShillingtonB, M SpitsB, S ReidA,
A
School of Sport Science, Exercise and Health, University of Western Australia, Perth, Australia.
Princess Margaret Hospital for Children, Perth, Australia
C
School of Paediatrics and Child Health, Australia
B
Objective: To investigate how a 10 week strength program impacts muscular strength and
morphology for children with CP.
Study design: A randomised controlled intervention study.
Study Participants: Fifteen children diagnosed with Spastic Diplegic Cerebral Palsy GMFCS I-II,
aged between 5-12 years (mean age= 8.52yrs, ±1.59) were enrolled in the study. Children were
block randomised by age, gender and GMFCS level to the training group (n=7) or control group
(n=8).
Methods: The training group undertook a 10 week home-based supervised strength training
program focusing on their lower limbs. Children completed up to 3 supervised sessions weekly.
The program was progressive, initially focussing on motor control and the establishment of
base strength and progressed to more complex functional movements reflecting the child’s
goals.
Isometric and isokinetic strength assessments of the knee flexor/extensor muscle groups were
completed using a Biodex System3 dynamometer (Biodex Medical Systems, Inc. Shirley, NY). A
1.5-T whole body MR unit (Sonata, Siemens) was used to acquire bilateral transverse plane
images. MR images were transferred to Mimics software (Version 9.0, Materialise, Leuven) for
manual digitisation of each muscle of the quadriceps and hamstring along the length of the
muscle, to ascertain muscle volume (MV) and cross sectional area (CSA).
Results: Children in the training group showed significant (p<0.05, ES=-0.84) increases in
quadriceps (m=26.97±64.90) and hamstring (m=18.02±31.71) isokinetic strength compared to
the control group (quadriceps m=-16.68 ±34.51; hamstring m=-8.57±34.63). Hamstring MV
increased significantly in the training group (change = 0.75cm3/cm) compared with the control
group (change = 0.25cm3/cm) (p=0.01, ES=-0.91). However, no significant difference in
167
quadriceps morphology was observed between the training and control groups (p>0.05; quads
MV ES=-0.44, CSA ES=-0.16).
Conclusion: Strength training resulted in significant improvements in isokinetic strength. The
improvements in strength may reflect improved patterns of muscle fibre recruitment and
utilisation, suggesting that short term strength training programmes alter muscle innervation,
not necessarily muscle morphology.
168
Presented at the Australasian Academy of Cerebral Palsy and Developmental. AusACPDM 6th
Biannual conference. 2012 Brisbane, QLD, Australia
The Immediate Effect of Botulinum Toxin Type-A on Muscle Morphology and Strength
in Children with Cerebral Palsy.
S WilliamsA, C ElliottC, J ValentineB, A GubbayB, M SpitsB, S ReidA.
A
School of Sport Science, Exercise and Health, UWA, Perth, WA, Australia.
Princess Margaret Hospital for Children, Perth, WA, Australia
C
School of Paediatrics and Child Health, UWA, Australia
B
Objectives: To investigate whether BoNT-A injections have an immediate effect on muscle
morphology and strength of the lower limbs in children with CP.
Study design: Single group repeated measures design.
Study Participants: Fifteen children with CP currently receiving BoNT-A for spasticity
management. All children were classified as Spastic Diplegic, GMFCS I-II, aged between 5-12
years (mean age= 8.52yrs, ±1.59, ten males and five females).
Methods: Children completed two assessments; 1) approximately 2 weeks prior to BoNT-A and
2) approximately 4-6weeks post injection. Children underwent strength assessments and a
muscle MRI at each time point. All children received BoNT-A treatment to the gastrocnemius
and a subset of five children also received treatment to the hamstrings.
A 1.5-T whole body unit (Sonata, Siemens) was used to acquire bilateral transverse images
from the ankle malleoli to iliac crest. MR images were transferred to Mimics software (Version
9.0, Materialise, Leuven) for manual digitisation of each muscle of the hamstring and
plantarflexor groups, to ascertain muscle volume (MV) and cross sectional area (CSA).
Isometric and isokinetic strength assessments of the knee flexor muscle group were completed
using a Biodex System3 dynamometer (Biodex Medical Systems, Inc. Shirley, NY). A hand held
dynamometer (HHD) (Model 01163, Lafayette Instrument Company) was used to determine
isometric strength of the plantarflexors.
Results: A significant decrease in isokinetic muscle work (p=0.03) was observed following
hamstring BoNT-A injection. However, no change in isometric strength was evident in the
plantarflexors. Whilst total muscle group morphology remained unchanged, individual muscle
alterations were evident. A significant decrease in medial gastrocnemius MV (p=0.001) and
significant increase in soleus MV (p=0.024) was observed following BoNT-A treatment.
169
Following hamstring treatment the CSA of semitendinosis was observed to decreased
significantly (p=0.01).
Conclusion: BoNT-A injections do not appear to have an immediate effect on total muscle
group morphology as assessed via MV and CSA. This work provides some evidence of
individual muscle decline and synergist compensation following treatment. Results reveal a
potential effect of BoNT-A on decreasing the muscles ability to perform work for some
children.
170
Presented at the American Academy of Cerebral Palsy and Developmental. AACPDM 65th
Annual meeting. 2011 Las Vegas, Nevada, USA.
*Received Mac Keith Press Promising Career Award for best paper.
The Immediate Effect of Botulinum Toxin Type-A on Muscle Morphology and Strength
in Children with Cerebral Palsy.
S WilliamsA, C ElliottC, J ValentineB, A GubbayB, M SpitsB, P ShipmanB, S ReidA.
A
School of Sport Science, Exercise & Health, University of Western Australia, Perth, WA,
Australia.
B
Princess Margaret Hospital for Children, Perth, WA, Australia
C
School of Paediatrics and Child Health, WA, Australia
Background/Objectives: Both spasticity and muscular weakness are significant impairments on
the ability to function for children with spastic Cerebral Palsy (CP). The application of
Botulinum Toxin Type-A (BoNT-A) in the management of spasticity is an established treatment
option for children with CP. Due to the mechanisms of BoNT-A, muscle weakness in the
targeted muscle is to be expected; however it is unknown if this weakness is related to altered
muscle morphology. This research aims to investigate whether BoNT-A injections have an
immediate effect on muscle morphology and strength of the lower limbs in children with CP.
Study design: Single group repeated measures design.
Study Participants: Fifteen children with CP currently receiving BoNT-A for spasticity
management. All children were classified as Spastic Diplegic, GMFCS I-III, aged between 5-12
years (x age= 8.52yrs, ±1.59, ten males & five females).
Study settings: Tertiary paediatric hospital setting.
Materials/Methods: Muscle morphology (muscle volume (MV) & cross sectional area (CSA)) of
the lower limb was assessed using Magnetic Resonance Imaging (MRI). A 1.5-T whole body unit
(Sonata, Siemens) was used to acquire bilateral transverse plane images from the ankle
malleoli to iliac crest. MR images were transferred to Mimics software (Version 9.0,
Materialise, Leuven) for digitisation. The slice areas of each muscle in the hamstring & plantar
flexor (PF) muscle groups were manually traced along the length of the muscle.
Strength assessments of the knee flexor muscle group were completed using a Biodex System3
dynamometer (Biodex Medical Systems, Inc. Shirley, NY). The assessments involved isometric
contractions with the knee flexed at 90°, & a series of isokinetic contractions at velocities of
171
60o/s & 90o/s. A hand held dynamometer (HHD) (Model 01163, Lafayette Instrument
Company) was used to determine maximal isometric strength of the PF in standardised
positions. Children completed two assessments; 1) approximately 2 weeks prior to BoNT-A &
2) approximately 4-6weeks post injection. Hamstring & gastrocnemius muscles were injected
with BoNT-A as clinically indicated through goal setting & clinical assessment.
Results: Minimal decreases in strength were evident after BoNT-A, but did not approach
statistical significance (p>0.05, x work & Isometric ES=0.29). No change in strength was evident
in the PF, however small changes occurred at the hamstrings particularly in measures of
isokinetic strength for some children with decrements of 9-12%.
There were no significant differences (p<0.05) in muscle morphology (MV or CSA) for the
hamstring or PF muscle groups across the two time points.
Conclusion/significance: This research indicates that BoNT-A injections are safe and do not
have an immediate effect on muscle morphology as assessed via MV and CSA. Similarly, no
significant decrease in strength is reported after BoNT-A, however results may reveal a
potential effect of BoNT-A on decreasing the muscles ability to perform work through range
for some children. Changes observed in work capacity are not a result of change in muscle
morphology, but instead signal the neurological effect of BoNT-A.
172
Presented at the American Academy of Cerebral Palsy and Developmental. AACPDM, 64th
annual meeting. 2010 Washington, DC, USA.
Does MRI-derived muscle size relate to strength in children with and without CP?
C ElliottA , C PitcherB, S WilliamsB, A KuenzelA, P ShipmanA, J ValentineA, S ReidB
A
Princess Margaret Hospital, Western Australia
B
School of Sports Science Exercise and Health, University of Western Australia
Background / Objective: Measures of muscle size are directly proportional to the maximum
force-generating capacity of muscles in adults (Akagi et al., 2009). However this relationship is
yet to be established in children. The aim of this study was to compare strength to muscle size
in typically developing children (TD) and children with spastic diplegic CP.
Study Design: A prospective cross sectional study with a normative comparison population.
Study participants and setting: Ten participants with spastic diplegia CP age range 6 – 10 years
(mean age 7.2y [SD 1.32y], GMFCS I-III) and twenty TD aged 5 to 11 years (mean age 7.5y
[SD1.74y] were recruited.
Exclusion criteria were orthopaedic surgery, neurosurgery or
Botulinum toxin injections within 5 months of testing.
Materials/Methods: Strength assessments were completed using a Biodex System-3
dynamometer (Biodex Medical Systems, Inc. Shirley, NY). Participants performed isometric
trials and a series of isokinetic concentric trials at 60° and 90°/sec. Axial spin-echo T1-weighted
MR images were acquired bilaterally from the level of the ankle malleoli to the iliac crest while
subjects lay prone in a 1.5T whole body magnetic resonance unit (Magnetom Sonata Maestro
Class, Siemens Medical Solutions, Erlangen, Germany). Muscles were manually segmented
using Mimics software (Version 9.0, Materialise, Leuven); these included the rectus femoris,
vastus lateralis, vastus medialis, semitendinosis, biceps femoris, and semimembranosis.
Muscle volume (MV) and muscle cross-sectional area (CSA) defined muscle size.
Results: Children with CP were weaker than their TD peers on all strength variables (p>0.003).
CSA of the hamstrings (t=3.34; p<.000) and quadriceps (t=6.18; p <.000) were smaller in
children with CP than their TD peers. A significant difference was established between the two
groups for hamstring MV (t=3.436; p <.002) but not for the quadriceps MV (t=2.976; p <.006).
The strongest relationship existed between isometric strength and MV for both the quadriceps
(CP r=.793, TD r=.77) and the hamstrings (CP r=.738, TD r=.84).
173
Conclusions / Significance: This research concurs with evidence that children with CP are
weaker and have smaller muscles than TD children. MRI-derived MV better predicts strength
capacity in both CP and TD children. Whilst TD children display the same size strength
relationship as adults, children with CP do not. Children with CP appear to be underpowered
relative to their muscle size. This data provides an understanding of muscle strength and size,
and further investigation is required of pathology of the muscles of children with CP
References: Akagi R, Takai Y, Ohia M, Kanehisa H, et al.; Muscle volume compared to crosssectional area is more appropriate for evaluating muscle strength in young and elderly
individuals. Age and Ageing 2009; 38: 1-6
Acknowledgments: The authors would like to acknowledge the support of; The Raine Medical
Research Foundation and UWA Research Development Awards.
174
Presented at the Australasian Academy of Cerebral Palsy and Developmental Medicine
(AusACPDM) Conference, Christchurch, New Zealand, 2010
The Relationship between Muscle Morphology and Strength in Children with and Without
Cerebral Palsy
Elliott C1, Reid S2 Pitcher C1&2, William, S1&2 Kuenzel A3, Valentine J1.
1
Department of Paediatric Rehabilitation, Princess Margaret Hospital for Children, Perth, WA,
Australia
2
Australia
3
Department of Diagnostic Imaging, Princess Margaret Hospital for Children, Perth, WA,
Australia
Objective: This research aims to establish the nature of the relationship between measures of
muscle morphology (muscle cross-sectional area-CSA and muscle volume as determined via
MRI) and measures of muscular strength (evaluated through isokinetic dynamometry) in
children with and without CP.
Design: Cross-sectional cohort study.
Method: Eight children with CP GMFCS level II & III aged 5 – 11 years (mean 6.38 years, SD
1.3), including 6 male and 2 females participated.
This data was compared to that of 18
typically developing children aged 5-11 years (mean 7.5 years, SD 1.72), including 8 males and
10 females.
Written informed consent was provided by all participating families. Bilateral
axial T1 MRI images of the thigh were performed using a 1.5T whole body magnetic resonance
unit (Signa, General Electric Medical Systems, Milwaukee). MR images were transferred and
isotropic voxel size obtained using a trilinear interpolation routine. The hamstrings were
manually traced and segmented in single slices and re-sampled using bilinear and cubic
interpolation to calculate muscle volume and cross-sectional area (CSA). CSA of each muscle
group was defined as the mean area of the three slices exhibiting the greatest muscle area.
Children performed strength assessments of knee flexors and extensors bilaterally using a
Biodex Dynamometer (System 3). Isokinetic assessments were completed at 60° and 90°/sec,
and children completed three consecutive trials at each velocity. Variables of interest included
peak torque/body mass (PT/BM), work/body mass (W/BM) and average power.
Results: The correlation between muscle volume and PT/BM was strong for typically
developing children (0.72), and weaker for children with CP (0.38). Similar correlations were
established between muscle CSA and PT/BM (typically developing=0.66; CP=0.44).
The
175
correlations between muscle morphology (volume and CSA) and muscle strength (W/BM and
power) were consistently higher in typically developing children compared to children with CP.
Conclusion: The moderate to strong correlation between muscle volume and torque in
typically developing children reflects the relationship identified in the adult population. This
relationship is not as strong in the population of children with CP indicating that children with
CP are under powered relative to the size of their muscle bulk.
176
Poster displayed at the Australian and New Zealand Society for Paediatric Radiology (ANZSPR),
2010, Margaret River, Western Australia
The Effectiveness of Pre-MRI Practice to Prepare Children for MRI Scans.
Williams S1&2, Reid S2, Valentine J1, Dwyer B3, Shipman P1, Elliott C1
1
Department of Paediatric Rehabilitation, Princess Margaret Hospital for Children, Perth, WA,
Australia
2
Australia
3
Department of Diagnostic Imaging, Princess Margaret Hospital for Children, Perth, WA,
Australia
Objective: To prepare children to complete successful MRI scans using MRI practice, thereby
reducing the need for general anaesthetic or sedation.
Method: Forty one children, 15 with Cerebral Palsy (mean 7.4 years, SD 1.6; 5 females, 10
males) and 26 typically developing children (mean age 7.4 years, SD 1.9; 14 females, 12 males)
aged 3-11 years took part in pre-MRI practice, prior to undergoing a lower limb anatomical
MRI at PMH. Participants received pre-MRI preparation within one week of having their MRI
scan. The training took 45minutes, and centred on familiarising the child with the procedure
using age appropriate play and education. The session included a short video that featured
other children explaining what happens and what to expect in an MRI. Children were
familiarised to the sound of the MRI machine, as well as developed other competencies
required for an MRI scan such as lying still for a period of time. The child’s learning was
reinforced with an individualised storybook and activity sheets.
Results: All Forty-one children successfully completed MRI’s without the need for sedation.
The children were able to lay still for a readable scan. Children were required to lay still for
6minutes at a time for scans. Twenty-one typically developing children and 9 children with
Cerebral Palsy have since returned for follow up scans, without the need for further training,
just re-familiarisation with the individualised story-book.
Conclusion: Anxiety related associations with MRI scans can be experienced in patients of all
ages, not just children24. However, for younger children, the unfamiliar environment, people,
equipment and the noise can be so overwhelming that scans are either not begun, are
incomplete or are unsuccessful because of movement artefact25. Patient preparation has
177
become commonplace for many medical procedures. MRI preparation with practice has the
potential to greatly reduce anxiety, and the need for expensive sedation and increase the
success rate of the MRI scans. Overall, practice MRI created a positive hospital experience for
the child and there family, and allows the development of skills which can be employed in
other areas of their life.
178
APPENDIX C- SUPPLEMENTARY DATA FOR CHAPTER THREE
MORPHOLOGICAL ALTERATIONS IN SPASTIC MUSCLES IMMEDIATELY FOLLOWING BOTULINUM NEUROTOXIN
TYPE-A TREATMENT IN CHILDREN WITH CEREBRAL PALSY.
MUSCLE MORPHOLOGY
Table 1 PRE and POST individual muscle volumes of the lower leg for 15 children (30 legs) receiving
BONT-A to the gastrocnemius muscle group. All values for muscle volume (MV) are expressed as %
of muscle volume (cm3) divided by tibia length (cm).
ID
WL _R
WL_L
TR_R
TR_L
TK_R
TK_L
SB_R
SB_L
RM_R
RM_L
MR_R
MR_L
MH_R
MH_L
LS_R
LS_L
LD_R
LD_L
JZ_R
JZ_L
JC_R
JC_L
JB_R
JB_L
DJ_R
DJ_L
ER_R
ER_L
DM_R
DM_L
Average
Gastroc.
1.88
1.43
3.71
3.67
2.97
2.76
2.35
2.16
2.64
2.64
5.05
4.54
3.04
2.59
2.27
1.57
1.93
1.99
4.47
3.97
2.57
3.08
3.49
3.48
2.39
2.25
3.86
4.06
3.62
3.49
3.00
Pre- BoNT-A injection
Soleus
PF total
2.57
4.45
2.09
3.52
4.22
7.93
4.26
7.93
3.49
6.46
3.78
6.55
2.21
4.55
2.76
4.93
4.30
6.93
4.45
7.09
6.40
11.45
7.59
12.13
3.94
6.98
4.35
6.94
4.70
6.97
2.80
4.38
2.83
4.76
3.24
5.23
5.25
9.73
5.55
9.52
3.62
6.19
3.88
6.96
4.01
7.50
4.23
7.71
3.77
6.17
3.90
6.15
5.71
9.58
6.84
10.90
6.36
9.98
6.62
10.11
4.32
7.32
DF
0.86
0.72
0.97
1.20
0.99
1.17
0.56
0.89
1.30
1.27
1.41
1.80
1.24
1.26
0.93
1.18
0.82
1.05
1.44
2.00
1.47
1.72
1.62
1.63
1.15
1.40
1.62
1.71
1.30
1.53
1.27
Gastroc.
1.97
1.40
3.35
2.92
2.45
2.67
2.27
2.14
2.42
2.78
4.50
4.36
2.71
2.50
1.93
1.35
2.56
2.09
3.81
3.70
2.58
3.13
3.55
3.58
2.08
1.79
3.77
4.20
3.65
3.09
2.84
Post BoNT-A injection
Soleus
PF total
2.55
4.51
2.03
3.43
4.58
7.93
4.42
7.35
4.15
6.60
3.53
6.20
2.41
4.68
2.78
4.92
4.28
6.69
4.17
6.95
6.49
10.99
8.11
12.47
3.82
6.54
5.06
7.57
4.85
6.78
2.86
4.21
3.61
6.17
3.67
5.76
4.97
8.78
5.60
9.30
3.86
6.44
4.23
7.36
4.14
7.69
4.30
7.87
4.16
6.24
4.37
6.16
5.73
9.50
6.74
10.94
6.09
9.74
6.28
9.37
4.46
7.30
DF
0.88
0.67
1.19
1.14
1.20
1.34
0.67
0.91
1.27
1.26
1.37
1.79
0.94
1.31
0.96
1.00
1.06
1.21
1.62
1.82
1.61
1.77
1.47
1.53
1.10
1.42
1.40
1.75
1.35
1.70
1.29
179
Table 2 PRE and POST individual muscle volumes of the thigh for 10 children (20 legs) receiving
BoNT-A to the gastrocnemius muscle group. All values are expressed as % of muscle volume (cm 3)
/femur length (cm).
ID
TR_R
TR_L
TK_R
TK_L
MR_R
LMR_L
MH_R
MH_L
LS_R
LS_L
LD_R
LD_L
JZ_R
JZ_L
JC_R
JC_L
JB_R
JB_L
DM_R
DM_L
Average
Med HS
3.00
2.85
2.81
2.62
5.34
5.22
3.21
3.01
3.00
2.49
2.82
2.74
5.28
5.07
3.63
3.53
3.28
3.29
3.71
3.52
3.52
Biceps
Total HS
Femoris
2.37
5.37
2.52
5.37
1.85
4.67
1.54
4.16
3.77
9.11
3.40
8.62
2.71
5.92
3.04
6.05
2.24
5.24
1.67
4.16
2.36
5.18
2.18
4.92
2.87
8.15
3.28
8.35
2.39
6.02
2.70
6.23
2.62
5.90
2.79
6.08
2.70
6.42
3.03
6.55
2.60
6.12
Quads
Med HS
10.60
12.95
10.91
11.03
18.05
18.41
11.82
12.05
11.49
9.53
8.61
8.26
15.67
15.01
10.15
11.46
12.39
13.03
14.26
14.45
12.51
3.43
2.88
3.10
2.81
5.18
5.30
3.04
3.14
3.08
2.43
2.95
2.89
4.61
5.11
3.91
3.64
3.35
3.62
3.33
3.33
3.56
Biceps
Total HS
Femoris
2.79
6.22
2.61
5.49
2.15
5.25
1.72
4.53
3.54
8.71
3.75
9.05
2.59
5.63
3.03
6.17
2.64
5.71
1.57
4.00
2.35
5.30
2.47
5.36
3.21
7.83
3.51
8.62
2.60
6.51
2.80
6.44
2.48
5.84
2.53
6.15
2.77
6.10
3.05
6.38
2.71
6.26
Quads
11.56
13.49
12.55
12.34
17.96
18.32
12.47
12.97
11.55
9.15
9.62
9.26
15.28
15.54
10.99
10.76
12.45
13.43
14.67
14.75
12.96
Table 3 PRE and POST individual muscle volumes of the thigh for 5 children (10 legs) receiving BoNTA to the medial hamstrings and gastrocnemius. All values are expressed as % of muscle volume
(cm3) /femur length (cm).
ID
WL _R
WL_L
SB_R
SB_L
RM_R
RM_L
DJ_R
DJ_L
DM_R
DM_L
Average
Med HS
2.54
2.42
2.67
2.57
3.30
2.87
2.49
2.62
3.71
3.52
2.87
Biceps
Total HS
Femoris
2.02
4.56
2.17
4.59
1.81
4.48
1.85
4.42
2.66
5.95
2.48
5.35
2.30
4.80
2.35
4.97
2.70
6.42
3.03
6.55
2.34
5.21
Quads
Med HS
10.29
10.06
10.40
10.82
11.60
11.44
15.86
14.92
14.26
14.45
12.41
2.20
2.47
2.65
2.55
2.37
2.83
2.53
2.56
3.33
3.33
2.68
Biceps
Total HS
Femoris
1.69
3.90
2.22
4.70
2.00
4.64
1.91
4.47
2.34
4.71
2.26
5.09
2.43
4.96
2.37
4.93
2.77
6.10
3.05
6.38
2.31
4.99
Quads
9.80
9.93
9.95
10.75
11.60
11.59
16.30
15.03
14.67
14.75
12.44
180
MUSCLE STRENGTH
Table 2 PRE and POST isometric peak torque for knee flexor and knee extensor strength, in 10
children (20 legs) receiving BoNT-A to the gastrocnemius muscle group. Values are normalised to
body weight.
Knee
Flexion
Knee
Extension
Knee
Flexion
Knee
Extension
TK_R
TK_L
TR_R
TR_L
MR_R
LMR_L
MH_R
MH_L
LS_R
LS_L
LD_R
LD_L
JZ_R
JZ_L
JC_R
JC_L
JB_R
JB_L
ER_R
ER_L
40.3
33.3
66
68.9
30
31.1
72.2
62.1
58.3
30.3
71.7
82.6
151.7
126.3
61.9
167.5
132.2
164.4
142.6
109.4
84.6
148.6
155.4
53.7
77.2
221.8
210.8
158.9
120
165.9
157.7
185.4
177.7
316
252.2
463.8
421.9
364.5
271.7
54.4
44.2
81.1
82.2
49
63
56.3
51.6
38.5
19.5
61.3
56.5
131.5
24.5
59.46
168.3
150.4
82
101.1
174.0
89.0
168.1
133.7
103.5
136.0
182.3
245.6
133.1
111.8
196.3
169.4
253.0
228.1
253.0
237.7
478.7
502.5
242.4
198.8
Average
83.86
205.86
72.36
211.85
ID
Table 3 PRE and POST isometric peak torque for knee flexor and knee extensor strength, in 5
children (10 legs) receiving BoNT-A to the medial hamstrings and gastrocnemius. Values are
normalised to body weight.
ID
Pre- BoNT-A
injection
Post BoNT-A
injection
Knee
Flexion
Knee
Extension
Knee
Flexion
Knee
Extension
WL _R
WL_L
SB_R
SB_L
RM_R
RM_L
DM_R
DM_L
DJ_R
DJ_L
65.4
60.0
67.1
58.9
68.8
57.4
52.6
53.8
63.6
79.2
261.3
179.7
193.8
208.2
180.1
214.0
167.1
170.3
240.5
256.0
78.6
50.4
48.2
28.6
51.5
42.2
64.4
59
75.1
62.9
197.6
250.2
185.4
175.1
248.5
260.4
173.6
181.1
294.8
255.7
Average
62.68
207.10
56.09
224.98
181
Table 4 PRE and POST values for plantar (PF) and dorsi flexor (DF) strength, in 15 children (30 legs)
receiving BoNT-A to gastrocnemius. Values are presented in kilograms.
ID
PF
DF
PF
DF
WL _R
WL_L
TR_R
TR_L
TK_R
TK_L
SB_R
SB_L
RM_R
RM_L
MR_R
MR_L
MH_R
MH_L
LS_R
LS_L
LD_R
LD_L
JZ_R
JZ_L
JC_R
JC_L
JB_R
JB_L
DJ_R
DJ_L
ER_R
ER_L
DM_R
DM_L
21.5
24.3
25.7
20.2
20.2
23.4
26.7
28.5
32.2
25
26.9
32.8
31
31.7
18.1
16.4
22.3
25
28.5
28.7
36.9
40.4
40.6
41.2
43.1
42.1
33.4
36.5
38.9
31.9
9.5
10.1
14.2
10.4
7.1
5.9
12.4
12.4
15.2
14.2
16.1
17.7
12.9
14.2
0
0
9.4
9.4
10.6
10.7
17.1
20.5
13
11.2
20.5
15.9
12.7
11.1
12.3
14.4
28.9
22.3
24.3
19.3
20.9
23.5
17.4
21.2
31.3
33
33.6
35.8
35.1
33.1
15.9
12.8
31.9
29.9
26.4
29.3
40
45.5
38.2
42.4
43.1
38.4
36.6
43.6
29.6
30.4
11.7
11.1
9.1
9.5
6.8
7.9
8.2
7.3
16.2
15.8
16.7
17.4
15.5
13.8
4.4
5.1
11.8
12.4
12.6
8.9
16.5
15.6
11.5
9.7
16.8
15.5
17.9
14.9
12.6
13.6
Average
29.8
12.0
30.5
12.2
.
182
FUNCTION
Table 5 PRE and POST values for the Timed Up and Go (TUG) (seconds) and the 6Minute Walk Test
(6MWT) (meters), in 10 children (20 legs) receiving BoNT-A to the gastrocnemius.
ID
TUG
6MWT
TUG
6MWT
JB
LD
TK
LS
JC
MH
TR
ER
MR
JZ
3.98
6
5.41
4.73
3.68
5.79
4.05
3.2
4.26
3.89
652
508
496.5
447.8
633
627.5
590.6
672
564
583.5
3.98
5.55
5.26
5.47
3.75
5.79
4.98
3.17
5.26
3.37
612.2
497.9
491.5
420.5
621.5
552
538
631
607.3
627
Average
4.50
577.49
4.66
559.89
Table 6 PRE and POST values for the Timed Up and Go (TUG) (seconds) and the 6Minute Walk Test
(6MWT) (meters), in 5 children (10 legs) receiving BoNT-A to the medial hamstrings and
gastrocnemius.
ID
TUG
6MWT
TUG
6MWT
SB
WL
DM
DJ
RM
6.16
4.46
3.95
4.08
5.14
407.5
500
649.4
583.9
423.3
5.76
3.88
4.68
3.98
5.09
392
559.16
653.9
525.7
457
Average
4.76
512.82
4.68
517.55
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APPENDIX D- PRINCESS MARGARET HOSPITAL ETHICAL APPROVAL
184
185
APPENDIX E- THE UNIVERSITY OF WESTERN AUSTRALIA ETHICAL APPROVAL
186
APPENDIX F- PARENT AND PARTICIPANT INFORMATION AND CONSENT FORMS
187
School of Sport Science, Exercise and Health
M408
The University of Western Australia
35 Stirling Highway Crawley
Western Australia 6009
Phone
Fax
Web
+61 8 6488
+61 8 6488 1039
www.sseh.uwa.edu.au
CRICOS Provider Code: 00126G
Parkway (Entrance No 3) Nedlands
Participant information Sheet
Strength Training for Children with Cerebral Palsy who are having Botox®
WHY?
Botulinum toxin helps to improve muscle tightness in children with cerebral palsy. Reduced muscle tightness makes it
easier to walk, and join in with activities with friends and family. Strong muscles are also just as important, and doing
special strength exercises can help to make walking and these activities even easier. This study will help us understand
how Botulinum toxin and strength training can help children with cerebral palsy.
WHO CAN HELP?
Children with cerebral palsy between the ages of 5 and 10 years
WHAT WILL HAPPEN?
You and your parent / guardian will come to the School of Sport Science, Exercise and Health at the University of Western
Australia to do lots of fun and interesting things. A physiotherapist will look at how tight your leg muscles are and how
much they move. Then you will have shiny markers put on your legs, so we can understand how you walk. You will do
some short walks and you will get to see yourself walking on the special computer. You will then sit in a big chair and
move your legs so we can see how strong your legs are. You will get to see what some of your leg muscles look like with a
special machine called an Ultrasound. And finally you will get to know about what will happen when you go to have an
MRI at the Children’s Hospital. With the help of your parent / guardian you will fill out two forms about the different
activities you do. You will spend about two-three hours at the University of Western Australia.
These are the
shiny markers
your will wear
on your legs
while you walk
This is the chair
you sit in when
we test how
strong
your
legs are
188
Then on another day you will actually get to have an MRI. An MRI takes lots of really great pictures of all the muscles in
your legs. It takes about 20mins, so you can even bring your favourite DVD to watch at the same time.
STRENGTH TRAINING
After your first visit, you will get your very own set of strength training exercises especially made for you to help you get
stronger. You will be able to do your exercises at your own home, with help from us as you go through your program. The
exercises will take about 30min, and you will need to do them 3 times a week to get the best out of your program.
WILL ANYTHING HURT?
Some children, but not many, find the shiny markers itchy. The tape used to stick the markers is special and if it does itch
it will not last for long. Sometimes you might find that you have slightly sore muscles the next day after working your leg
muscles really hard, this won’t last more than a day. The MRI makes a loud noise when it takes its pictures, but you get to
wear headphones that let you listen to your DVD, and your Mum or Dad can stay with you the whole time.
WHAT ELSE DO I NEED TO KNOW?
You do not have to participate in this research. You are free to pull out from the study at any time for any reason. You do
not need to give a reason for pulling out. All your information will only been seen by us, we will not share it with other
people. If we publish the results of this research your name or identity will not be revealed.
PARTICIPANT BENEFITS
If you participate in this study you will be provided with a report of your muscle tightness, muscle strength and how much
your legs move. You will also get your very own set of strength exercises that will help to make you stronger in the
muscles that are important for you. Your results will also help improve our understanding of how Botulinum toxin and
strength training can help other children with cerebral palsy.
If you would like any more information about this study please feel free to contact one of the research team. We are
happy to answer your questions.
Yours sincerely,
Sîan Williams
PhD Candidate
Ph: **********
[email protected]
Dr. Siobhán Reid
Research Supervisor
Dr. Catherine Elliott
Research Supervisor
Ph: **********
[email protected]
Ph: **********
[email protected]
Dr. Anna Gubbay
Clinical Supervisor
Ph: **********
[email protected]
Nadine Williams
Clinical Supervisor
Ph: **********
[email protected]
189
School of Sport Science, Exercise and Health
M408
The University of Western Australia
35 Stirling Highway Crawley
Western Australia 6009
Phone
Fax
Web
+61 8 6488
+61 8 6488 1039
www.sseh.uwa.edu.au
CRICOS Provider Code: 00126G
Parkway (Entrance No 3) Nedlands
INFORMATION SHEET
Lower Limb Strength Training for Children with Cerebral Palsy receiving Botulinum Toxin
Purpose
Botulinum Toxin (Botox) has been proven to be a safe and effective treatment of spasticity in children
with Cerebral Palsy (CP). Botox® has been used at Princess Margaret Hospital for the past ten years to
help children with CP.
Muscular weakness has been identified as an area of concern for children with CP, with links to
impaired functional ability. Strength training has been shown as an effective method of addressing
this, with reported benefits to muscular strength extending to functional and psychosocial benefits.
With both spasticity and muscular weakness acting as significant impairments on functional ability,
this research will investigate the effects of combining Botox® therapy and targeted lower limb strength
training for children with CP.
This study aims to look at strength, tone, muscle morphology, function and quality of life of all
children with CP. Finally, this study will investigate the most effective timing of strength training
relative to children having Botox®. The data from these children will be compared to see if targeted
lower limb strength training a) should be implemented into future therapy for children with CP, and b)
when it should be implemented relative to Botox® injections.
PARTICIPANT INCLUSION CRITERIA
All participants must meet the following inclusion criteria to be eligible for this study:
Be diagnosed with Cerebral Palsy
Be between the ages of 5 and 10 years
Have the ability to follow simple instructions
Be able to walk indoors and outdoors on a level surface (with or without the use of a mobility device).
Benefits
It is anticipated that the addition of targeted strength training to current Botox® treatment
regimens will result in benefits to strength, gait, functional ability and overall quality of life for
children with CP. Your child will receive an individualized lower limb strength training program,
which will be monitored and adjusted to suit your child’s needs. In addition to this, your child will
receive additional clinical assessments that will be passed on to their hospital records and
provide valuable information in monitoring your child’s progress.
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This research will help with the development of ‘best practice’ standards of care for the long term
use of Botox® in children with CP. The research has the potential to improve current treatment
options available to children with CP.
PROCEDURES
Your child’s participation will require you and your child to attend four assessments, each
involving a session at the University of Western Australia (UWA) and a visit to Princess Margaret
Hospital (PMH) over a 26 week time period. Sessions at UWA will take approximately 3 hours,
with the visit to PMH taking less than 30minutes. The visit to UWA and PMH will be within 1 week
of each other. Assessment schedule is as follows:
Assessment 1: 10 weeks before your child’s scheduled upcoming Botox® injection,
Assessment 2: Within 1 week before receiving Botox®,
Assessment 3: 1-2 weeks after receiving Botox®
Assessment 4: 10 weeks after Assessment 3
UWA
At the testing session at The University of Western Australia, strength assessments, gait motion
analysis and clinical assessments will be performed.
Strength will be assessed on a specialized piece of equipment which records muscle strength.
Gait motion analysis will be assessed using a specialized infrared camera system. Reflective markers
will be placed on your child’s skin at selected landmarks of the trunk and lower limb. Your child will
then be asked to walk for 10 meters (a number of trials will be conducted) in a testing area with 7
infrared cameras recording their lower limb movement.
Ultrasound measures of the size and length of two of your child’s leg muscles will be recorded. The
ultrasound pictures are taken with a probe above the muscles on the skin surface. Your child will get
to lie down and rest during this procedure which will take about 15-20mins. Most children find it
relaxing, rather like a muscle massage.
Lower limb anthropometric measures (lengths, breadths and circumferences), range of movement and a
clinical assessment of spasticity will all be completed in the manner of a full physiotherapy clinical
assessment.
You and your child will be asked to complete a series of questionnaires relating to the physical abilities of
your child and relate to quality of life, participation and activity.
Also at UWA, your child will be familiarized with what will happen for their Magnetic Resonance Image
(MRI) scan. This will be done by discussion of pictures in a storybook about having an MRI, and an
opportunity to practice skills required in an MRI through play and simulation. The session includes
listening to the sounds of the MRI unit, wearing headphones and watching a DVD of a child having an MRI.
As a parent you will have the opportunity to ask questions during the practice session and discuss
whether you would like to be in the room with your child when they have their MRI scan.
PMH
Following the session at UWA, the same person who did the MRI training will meet you at PMH for your
child’s MRI scan. MRI is an advanced technology that lets your doctors see muscles and joints. The MRI
scan will be used to provide excellent quality images of your child’s muscles. Your MRI appointment in the
Department of Radiology at PMH will take approximately 30mins. Your child can take along a favourite CD
or DVD to watch whilst the scan is happening, and you can stay in the room the whole time. You child will
have two scans each taking approximately 6 minutes, during this time your child will have to lie very still.
One scan will take pictures of the top of the legs, and the second scan will take pictures of the bottom of
the legs
Strength Training
Your child will be provided with an individualized strength training program that will target specific
muscles of lower limb including those injected with Botox®. The strength training will be a home based
program that will take no longer than 30 minutes per session. Your child will be required to complete 3
sessions per week (e.g. Mon, Wed, Fri), for a total of 10 weeks. The program will be developed either
between assessment 1 and 2, OR between assessments 3 and 4. You and your child will receive regular
contact and assistance with the program to help with progression of the training exercises and any
problems should they arise.
RISKS / RESTRICTIONS
Strength training
Strength training may result in slight muscular soreness; however this will be temporary and minimal.
Gait analysis
There is a slight risk of skin irritation from the adhesive tape that attaches markers to the skin. The tape is
low-allergenic and any irritation experienced will be short term. A very small percentage of children
experience these skin reactions.
Magnetic Resonance Imaging
MRI is very safe; in fact it makes use of natural forces and has no known harmful effects. It’s important to
know that MRI will not expose you or your child to radiation.
Because MRI machines use a strong magnetic field metal objects can interfere with the exam. It is
important that your child does not have any jewellery on them when they do the scan or any metal on
their clothing (zips, studs or glittery writing). You will complete a formal sheet that asks whether or not
your child has any other forms of metal that may be interfered with in the MRI e.g. pacemaker, metal
implants, cochlear implants etc.
192
If you would like to be in the room with your child while they have a scan you must also let the doctor
know if you have any of the above and make sure you have no metal objects on. There are no restrictions
for your child after the scan and they can go right back to their everyday activities. Often children will feel
very well rested after an MRI as they have been lying down doing absolutely nothing.
PARTICIPANT RIGHTS
Participation in this research is voluntary and you are free to withdraw your child from the study at any
time and for any reason, without prejudice in any way. You need give no reason or justification for such a
decision. However, all research data has to be retained even in the event of withdrawal from a study.
If you withdraw from the study this will not prejudice your status and rights as a patient of Princess
Margaret Hospital. Your child’s participation in this study does not prejudice any right to compensation,
which you may have under the statute of common law.
Participant confidentiality will be respected at all times. The results of this research may be published,
however neither your child’s name nor identity shall be revealed, all data will be coded so as to preserve
the identity and confidentiality of your child.
If you have any queries or questions regarding this information, please do not hesitate to contact us to
discuss. If you would like to make a complaint about the conduct of this study please contact Dr Geoff
Masters, Executive Director of Medical Services on 9340 8245.
Thank you for your time and consideration.
Yours sincerely,
Sîan Williams
PhD Candidate
Ph: **********
[email protected]
Dr. Siobhán Reid
Research Supervisor
Ph: **********
Dr. Catherine Elliott
Research Supervisor
Ph: **********
[email protected]
[email protected]
Dr. Anna Gubbay
Clinical Supervisor
Ph: **********
[email protected]
Nadine Williams
Clinical Supervisor
Ph: **********
[email protected]
193
FORM OF CONSENT
PLEASE NOTE THAT PARTICIPATION IN RESEARCH STUDIES IS VOLUNTARY AND SUBJECTS
CAN WITHDRAW AT ANY TIME WITH NO IMPACT ON CURRENT OR FUTURE CARE.
I ............................................................................................ have read the information explaining the study entitled
Given Names
Surname
Lower Limb Strength Training for Children with Cerebral Palsy receiving
Botulinum Toxin
I have read and understood the information given to me. Any questions I have asked have been
answered to my satisfaction.
I agree to allow......................................................................................................................................................................................
(full name of participant and relationship of participant to signatory)
to participate in the study.
I understand my child may withdraw from the study at any stage and withdrawal will not interfere
with routine care.
I agree that research data gathered from the results of this study may be published, provided that
names are not used.
Dated ...........................................
Parent or Guardian’s Signature ....................................................
Child’s Signature .............................................................................
(Where appropriate)
I, ........................................................................... have explained the above to the signatories who stated that
(Investigator’s full name)
he/she understood the same.
Signature ...............................................................................................
The Human Research Ethics Committee at the University of Western Australia requires that all
participants are informed that, if they have any complaint regarding the manner, in which a research
project is conducted, it may be given to the researcher or, alternatively to the Secretary, Human
Research Ethics Committee, Registrar’s Office, University of Western Australia, 35 Stirling Highway,
Crawley, WA 6009 (telephone number 6488-3703). All study participants will be provided with a copy of
the Information Sheet and Consent Form for their personal records.
194
APPENDIX G- SELECTIVE CONTROL ASSESSMENT OF THE LOWER EXTREMITY (SCALE)
APPENDIX H- CANADIAN OCCUPATIONAL PERFORMANCE MEASURE (COPM)
195
196
197
198
APPENDIX I- ASSESSMENT OF LIFE HABITS (LIFE-H)
199
200
201
202
203
204
205
APPENDIX J- CEREBRAL PALSY QUALITY OF LIFE QUESTIONNAIRE (CP-QOL)
206
207
208
209
210
APPENDIX K - EXAMPLE OF A 10 WEEK HOME BASED STRENGTH PROGRAM
1) You are aiming to do this 3 times each week! Perhaps set aside 3 days that you will do every week (e.g.
Monday, Wednesday and Friday)
2) Remember to do your stretches before EVERY session!
3) Follow the exercises set out for you for the week that you are up to, if you have trouble doing any of
the sets, write down what you did manage to do.
4) At the end of every session, you can put a sticker on your chart to show that you have completed your
session. You can see all the hard work you have done by how many stickers your have at the end!
5) Have lots of fun!
If you get stuck or need any help at all please call Sîan on ************
211
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I aim to improve on ….
1)
How fast I can run over short distances (sprinting)
2)
How fast I can run for longer distances (endurance running)
3)
The distance that I can kick the ball for ruby
The main muscles I will be working on are……
 The muscles in my legs that will help me run fast.
 The muscles in my legs that will help me run fast over a long distance.
 The muscles in my legs that will help me kick a ball further.
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Each week, put a sticker on the days you do your strength exercises
Week
1
2
3
4
5
6
7
8
9
10
Sunday
June
Monday
Tuesday
Wednesday
27th
28th
29th
30th
July
4th
5th
6th
July
11th
12th
July
18th
July
Thursday
July
Friday
Saturday
1st
2nd
3rd
7th
8th
9th
10th
13th
14th
15th
16th
17th
19th
20th
21st
22nd
23rd
24th
25th
26th
27th
28th
29th
30th
31st
st
2nd
3rd
4th
5th
6th
7th
th
9th
10th
11th
12th
13th
14th
August
1
August
8
August
15th
16
th
17th
18th
19th
20
August
22nd
23rd
24th
25th
26th
27
August
29th
30th
31st
1st
2nd
Sep
th
21
st
th
28th
3rd
4th
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Stretches: To be done before every session!!!
Hips
The helper supports the leg at the knee and heel, and brings the knee
toward the chest. Hold for 15-20sec. Return the leg to starting position and
repeat with the other leg.
Hamstrings
The person who is helping place one hand above the knee to keep it
straight and the other hand under the heel. Keeping the leg straight, slowly
raise the leg until a stretch is felt at the back of the thigh. Be sure to keep
the other leg flat and hips down during the stretch. Hold for 15-20sec.
Return the leg to starting and repeat with the other leg.
Quadriceps
Lie on your stomach, with legs together bend your knee. Hold your ankle
with one hand and pull your heel to your bottom. Hold for 15-20sec.
Return the leg to starting and repeat with the other leg.
Plantar/Dorsi
Sit on the floor with the knee bent and the heel on the floor. Pull up on
your toes, or get your helper, to stretch the arch of the foot. Hold for 1520sec. Repeat, with a straight leg.
Flexors
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214
******* Strength Program Week 1
*Tip* When applying manual resistance, you want him to be able to push all the way through his range, but he has to work for it!
Exercise
Description
Repetitions
Resistance/ weight
Hip flexion
(Hip
bends)
Performed one leg at a time. Lay on back, with legs out straight.
Slowly bring knee up to chest, and lower.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
Manual resistance applied
against the thigh as they
bring the knee up to the
chest.
Performed one leg at a time. Lying on stomach, bend knee to
bring foot up to bottom, then lower back down to ground.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
Manual resistance with hand
on the back of the lower leg
as they push up, and then on
the front of the leg (pushing
up) as they push down.
Hamstring
curl
Seated Leg
Extension
Performed one leg at a time. Sit up straight in a chair, with feet
flat on the floor. Keeping knees together, straighten out one leg
all the way out, tightening your thigh muscles. Slowly lower foot
back down to the floor.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
Manual resistance with hand
pressing down on the leg (at
the ankle) as it rises up.
‘Superman’
Performed one leg at a time Lying on stomach, keep legs straight,
slowly raise leg of ground, trying to keep the hips square on the
ground. Hold for 3sec then lower.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
No resistance.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
No resistance.
Side Leg
Raises
Lay on your side on the floor, with the top leg raised up on a
chair/step. Lift the bottom leg off the floor as high as possible,
keeping the knee straight. Slowly lower the leg back to the
starting position.
215
Lay on your side with legs straight. Lift the top leg completely
away from the lower leg. Careful not to roll over onto your front
or back. Hold and return to the starting position.
215
**** ****Strength Program Week 2
Exercise
Description
Repetitions
Resistance/ weight
Hip flexion
(Hip bends)
Performed one leg at a time. Lay on back, with legs out straight. Slowly bring
knee up to chest, and lower.
.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
Attach weights
around ankles.
1kg
Performed one leg at a time. Lying on stomach, bend knee to bring foot up to
bottom, then lower back down to ground.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
Attach weights
around ankles.
1kg
Seated Leg
Extension
Performed one leg at a time. Sit up straight in a chair, with feet flat on the
floor. Keeping knees together, straighten out one leg all the way out,
tightening your thigh muscles. Slowly lower foot back down to the floor.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
Attach weights
around ankles
1kg
‘Superman’
Lying on stomach, keep legs straight, slowly raise one leg of ground, trying to
keep the hips square on the ground. Hold for 3sec then lower.
3x12
Hamstring
curl
Lay on your side on the floor, with the top leg raised up on a chair/step. Lift
the bottom leg off the floor as high as possible, keeping the knee straight.
Slowly lower the leg back to the starting position.
Side Leg
Raises
3x10
Lay on your side with legs straight. Lift the top leg completely away from the
lower leg. Careful not to roll over onto your front or back. Hold and return to
the starting position.
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**** ***** Strength Program Week 3
Exercise
Description
Repetitions
Resistance/ weight
Seated Hip
flexion
(hip bends)
Sitting on a chair with feet square on the ground, one leg at a time, slowly
raise knee up to chest, hold for 3 sec, lower.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
Attach weights around
ankles. (1kg)
Seated Leg
Extension
Performed one leg at a time. Sit up straight in a chair, with feet flat on the
floor. Keeping knees together, straighten out one leg all the way out,
tightening your thigh muscles. Slowly lower foot back down to the floor.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
ankles. (1.5kg)
Hamstring
curl
3x12
ankles. (1kg)
Pelvis bridge
Lay on back with knees bent up, feet are on the ground. Keeping shoulder
blades on the ground. Slowly lift your bottom pushing through your feet,
until your knees, hips & shoulders are in a straight line. Tighten your bottom
muscles as you do this. Hold for 3 seconds then slowly lower your bottom
back down.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
No weights.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
0.5kg
Side Leg
Raises
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Exercise
Description
Repetitions
Resistance/ weight
Seated Hip
flexion (hip
bends)
Sitting on a chair with feet square on the ground, one leg at a time, slowly
3x12
ankles. (1kg)
3x15
Low weights (0.5kg)
Hamstring
curl
Seated Leg
Extension
Sit up straight in a chair, with feet flat on the floor. Keeping knees together,
straighten out one leg all the way out, tightening your thigh muscles. Slowly
lower foot back down to the floor.
3x15
Low weights (1kg)
Pelvis bridge
until your knees, hips & shoulders are in a straight line. Tighten your bottom
muscles as you do this. Hold for 3 seconds then slowly lower your bottom
back down.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
Weights resting on
tummy.
1kg
3x12
0.5kg
Side Leg
Raises
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Exercise
Description
Repetitions
Resistance/ weight
Seated hip
flexion
(Hip bends)
Sitting on a ball with feet square on the ground, one leg at a time, slowly
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
Attach weights
around ankles (1kg)
Hamstring
curl
Performed one leg at a time. Lying on stomach, bend knee to bring foot up
to bottom, then lower back down to ground
3x6
Heavy weights
(1.5kg)
Seated leg
extension
3x6
Heavy weights
(1.5kg)
Pelvic bridge
until your knees, hips and shoulders are in a straight line. Tighten your
bottom muscles as you do this. Hold for 3 seconds then slowly lower your
bottom back down.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
Lift and extend one
leg so that it is
straight out, hold,
lower and repeat
with the other leg.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
1kg
Side leg
raises
Lay on your side with legs straight. Lift the top leg completely away from
the lower leg. Careful not to roll over onto your front or back. Hold and
return to the starting position.
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Exercise
Description
Repetitions
Resistance/ weight
Seated Hip
flexion
(Hip bends)
Sitting on a ball with feet square on the ground, one leg at a time, slowly
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
ankles. (1kg)
3x15
Low weights (0.5kg)
Hamstring
curl
Seated Leg
Extension
3x15
Low weights (1kg)
Pelvis bridge
Lay on back with knees bent up, feet are on the ball. Keeping shoulder blades
on the ground. Slowly lift your bottom pushing through your feet, until your
knees, hips and shoulders are in a straight line. Tighten your bottom muscles
as you do this. Hold for 3 seconds then slowly lower your bottom back down.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
No weights.
Standing
Theraband
hip flexion.
Standing at a bench or chair for balance, with Theraband around your ankle
so that it is pulling leg back. Keeping your back & knee straight, slowly take
your leg forwards, like you are kicking a ball. Hold position &lower back to
starting position.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
Theraband. Attached
around ankle to pull leg
backwards.
Standing Hip
Abduction
Begin by standing at a bench or table for balance. Keeping your back & knee
straight and foot facing forwards, slowly take your leg to the side tightening
the muscles at the side of your thigh. Hold for 3 seconds & lower.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
0.5kg
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221
Exercise
Description
Repetitions
Resistance/ weight
Swiss ball
squat
Standing against a wall with the Swiss ball between back and the wall, and legs
slightly in front of the body. Keeping it slow and controlled, lower down to a squat
(knees ~90°) and then rise back up to a standing position. Knees should stay in line
with the legs.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
No weights. Keep it
slow.
Standing
Hamstring
curl
Standing at a bench or chair for balance, one leg at a time, bend knee so that foot
comes as high as you can up to your bottom. Hold for 3 sec, lower.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
1kg
Seated Leg
Extension
straighten out one leg all the way out, tightening your thigh muscles. Slowly lower
foot back down to the floor.
3x6
Heavy weights
(2kg)
Pelvis bridge
Lay on back with knees bent up, feet are on the ball. Keeping shoulder blades on
the ground. Slowly lift your bottom pushing through your feet, until your knees,
hips and shoulders are in a straight line. Tighten your bottom muscles as you do
this. Hold for 3 seconds then slowly lower your bottom back down.
3x12
No weights.
Standing
Theraband
hip flexion.
Standing at a bench or chair for balance, with Theraband around your ankle so
that it is pulling leg back. Keeping your back & knee straight, slowly take your leg
forwards, like you are kicking a ball. Hold position &lower back to starting
position.
3x12
Theraband.
Attached around
ankle to pull leg
backwards.
Standing Hip
Abduction
Begin by standing at a bench or table for balance. Keeping your back & knee
straight and foot facing forwards, slowly take your leg to the side tightening the
muscles at the side of your thigh. Hold for 3 seconds & lower.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
1kg
221
Exercise
Description
Repetitions
Resistance/ weight
Swiss ball
squat
Standing against a wall with the Swiss ball between back and the wall, and legs slightly
in front of the body. Keeping it slow and controlled, lower down to a squat (knees ~90°)
and then rise back up to a standing position. Knees should stay in line with the legs.
3x12
No weights. Keep it
slow.
Lunges
Begin standing with one leg positioned in front & one leg behind as shown in the
picture. Slowly lower your body until your front knee is at a right angle. Try to keep your
knee in line with your middle toe & your feet facing forward. Keep the movement slow
& controlled.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
No weight
Standing
Hamstring
curl
Standing at a bench or chair for balance, one leg at a time, bend knee so that foot
comes as high as you can up to your bottom. Hold for 3 sec, lower.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
1kg
Standing.
Leg flexion
‘kicks’
Standing at a bench or chair for balance, with weights attached at the ankle. Standing
up as straight as you can, kick as high up as you can. As if you are kicking a big ball as far
away as you can.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
Attach weights
around ankles. 1kg
Pelvis
bridge
Lay on back with knees bent up, feet are on the ball. Keeping shoulder blades on the
ground. Slowly lift your bottom pushing through your feet, until your knees, hips and
shoulders are in a straight line. Tighten your bottom muscles as you do this. Hold for 3
seconds then slowly lower your bottom back down.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
Weights on tummy
1kg
Side step
Standing up nice and tall with feet facing forwards, take a side step without twisting
your body to the side. Repeat side steps in both directions.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
1kg
Obstacle
course
222
15m x 10m area
1: Sit to stand  x3
2: Sprint run
2x
3: Jumps
4: Sprint Run
5: High Knee Walking
6: Run 1 whole lap
Sprint run

High knee
Walking
Jumps
Sprint run
222
Exercise
Description
Repetitions
Resistance/ weight
Swiss ball
squat
Standing against a wall with the Swiss ball between back and the wall, and legs slightly in
front of the body. Keeping it slow and controlled, lower down to a squat (knees ~90°) and
then rise back up to a standing position. Knees should stay in line with the legs.
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
Holding on to
weights
Lunges
Begin standing with one leg positioned in front & one leg behind as shown in the picture.
Slowly lower your body until your front knee is at a right angle. Try to keep your knee in
line with your middle toe & your feet facing forward. Keep the movement slow &
controlled.
3x12
No weight
Pelvis
bridge
3x12
Weights on tummy
1kg
Standing.
Leg flexion
‘kicks’
Standing at a bench or chair for balance, with weights attached at the ankle. Standing up
as straight as you can, kick as high up as you can. As if you are kicking a big ball as far
away as you can.
3x12
Attach weights
around ankles. 1kg
Duradisc
Side step
with squat
Obstacle
course
Stand with both feet on Duradisc and try to stay balanced for 30 seconds!
Standing up nice and tall with feet facing forwards, take a side step without twisting your
body to the side and square. Repeat side steps in both directions.
223
15m x 10m area
2: Sprint run
3x
3: Jumps
4: Sprint Run
6: Run 1 whole lap
3 x30sec
Day 1: 3x6
Day 2: 3x8
Day 3: 3x10
1kg
Sprint run

High knee
Walking
Jumps
Sprint run
223
Exercise
Description
Repetitions
Swiss ball
squat
Standing against a wall with the Swiss ball between back and the wall, and legs slightly in
front of the body. Keeping it slow and controlled, lower down to a squat (knees ~90°) and
then rise back up to a standing position. Knees should stay in line with the legs.
3x12
Holding on to
weights
Pelvis
bridge
3x12
Weights on
tummy
1kg
Kicks
with
Weights
Standing at a bench or chair for balance, with weights attached at the ankle. Standing up as straight as you
can, kick as high up as you can. As if you are kicking a big ball as far away as you can.
Duradisc
Stand with both feet on Duradisc and try to stay balanced for 30 seconds!
Side step
with
squat
Obstacle
course
Standing up nice and tall with feet facing forwards, take a side step without twisting your
body to the side and square. Repeat side steps in both directions.
15m x 10m area
2: Sprint run
4x
3: Jumps
4: Sprint Run
6: Run 1 whole lap
Resistance/ weight
3x 12
Attach weights
around ankles. 1kg
3 x30sec
3x12
1kg
Sprint run

High knee
Walking
Jumps
Sprint run
224
224

Lower Limb Strength Training for Children with Spastic Diplegic

Transcription

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