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This Is the Title of My Thesis A Systematic Review of the Effectiveness of Interventions (Pharmaceutical and Psychosocial) for Cognitive and Learning Impairments in Children Diagnosed with a Brain Tumour Lisa-Jane Keegan Submitted in accordance with the requirements for the degree of Doctor of Clinical Psychology (D. Clin. Psychol.) The University of Leeds School of Medicine Academic Unit of Psychiatry and Behavioural Sciences September 2014 The candidate confirms that the work submitted is her own and that appropriate credit has been given where reference has been made to the work of others This copy has been supplied on the understanding that it is copyright material and that no quotation from the thesis may be published without proper acknowledgement. © 2014 The University of Leeds and Lisa-Jane Keegan (Optional) The right of Lisa-Jane Keegan to be identified as Author of this work has been asserted by her in accordance with the Copyright, Designs and Patents Act 1988 2 ACKNOWLEDGEMENTS I am sincerely grateful for the help of Professor Stephen Morley and Dr Matthew Morrall, without their support, time and patience this thesis would never have been possible. A big thank you to Miss Rosa Reed-Berendt (Research Assistant), Mr Paul Farrington (Psychologist in Forensic Training), Miss Elizabeth Neilly – Health Faculty Team Librarian, Ms Janet Morton – Education Faculty Team Librarian, Drs Picton, Wilkins and Elliott - Consultant Paediatric Oncologists, Dr Livingston - Consultant Paediatric Neurologist at The Leeds Teaching Hospitals NHS Trust, Miss Helen Stocks, Miss Kate Ablett and Dr Stanley, Consultant Child & Adolescent Psychiatrist, Leeds Community Healthcare NHS Trust, Suzanne Donald (Honorary Research Assistant) and Michael Ferriter- Lead for Research, Forensic Division, Nottinghamshire Healthcare NHS Trust; who have supported me to achieve my goal. A huge thank you to David, Lucy, Lee Lou and Colin; for their constant support, understanding and unconditional love. Without their motivation this thesis would never have been completed. Finally I would like to dedicate this thesis to my late father and mother, who never saw my dream become a reality. 3 ABSTRACT Tumours of the brain and the central nervous system (CNS) account for a quarter of all childhood cancers. Despite being a rare condition, it is the most frequent cause of death from disease in children aged 1-14 years, and accounts for just under a fifth of all bereavements in childhood. Recent medical advancements together with improvements in neurosurgery, radiation therapy and chemotherapy have facilitated earlier diagnosis. This has resulted in an increase in the aggregated survival rates of children diagnosed with brain tumours. As a result, children are living longer with greater neurocognitive morbidity. Statistics indicate that 40-100% of long-term survivors of a brain tumour will demonstrate some degree of cognitive dysfunction. Hence, the National Health Service (NHS) and other international health care providers are increasingly focusing on the rehabilitation needs and quality of survivorship of this population. The objectives of this thesis are to identify and evaluate the effectiveness of interventions (pharmaceutical and psychosocial) for cognitive and learning impairment within a paediatric neurooncology population. This will be addressed via a systematic review of all current research using a selection of Electronic Databases. The result of which will hope to provide a guide for appropriate service provision to address long-term neuro-rehabilitation and psychological needs in the future. A limited number of studies were retrieved in this systematic review; only three studies met the inclusion criteria. Thus, a narrative review resulted in limited conclusion about the effectiveness of psychosocial and pharmaceutical interventions on neurocognitive and learning impairments in a paediatric brain tumour population. Of the studies retrieved, all demonstrated promising results for the future of paediatric rehabilitation. However, it is the limited number of studies retrieved that is of most interest, highlighting a very small 4 evidence base and potentially problematic research design. Solutions to these difficulties are suggested. 5 TABLE OF CONTENTS TABLE OF CONTENT ACKNOWLEDGMENTS ............................................................................................. 3 ABSTRACT .................................................................................................................. 4 TABLE OF CONTENTS ............................................................................................. 6 LIST OF FIGURES ........................................................................................................ 10 LIST OF TABLES ........................................................................................................ 11 ABBEREVIATIONS ………………………………………………………........... 12 CHAPTER ONE: INTRODUCTION ....................................................................... 13 1.1 Neurocognitive and Learning Deficits …………………................................. 14 1.1.1 Cognitive Functioning ……………………………………........................... 14 1.1.2 Academic Attainment …………………………………………………….. 16 1.1.3 IQ ............................................................................................................ 16 1.2 Tumour Type and Known Deficits ……………………………........................ 17 1.3 Development of the Brain …………………………........……………………... 22 1.3.1 Plasticity and the Early Vulnerability Hypothesis …….....………......... 24 1.3.1.1 Early Vulnerability Hypothesis …………………………................ 24 1.3.1.2 Age-Based Plasticity ………………………………………........... 25 1.4 Primary Intervention .............................................................................................. 26 1.4.1 Neurosurgery …………………...…….......................................................... 27 1.4.2 Radiotherapy ………………………………………..................................... 28 1.4.2.1 Armamentarium of Radiotherapy ……………................................. 28 1.4.2.2 Limitations of Radiotherapy ……………...................................... 30 1.4.3 Chemotherapy ……………………………………...................................... 32 1.5 Survivorship and Wellbeing ………………………..........................…………... 36 1.6 Moderators ……………………………………………......................................... 37 1.6.1 Age ………………………………………………........…………............ 37 1.6.2 Time since Treatment …………………..................................................... 39 1.6.3 Resilience …………………………………………...................................... 40 1.6.3.1 Cognitive Reserve …………………….............................................. 40 1.6.3.2 Passive Models ……………………………....................................... 40 1.6.3.3 Active Models …………….......................…………...................... 41 1.7 Aims and Objectives of the Systematic Review …………………..................... 41 CHAPTER TWO: SCOPING ................................................................................... 43 6 2.1 Identifying the Research Question ...................................................................... 43 2.2 Identifying Relevant Studies .............................................................................. 43 2.2.1 Rehabilitation and Outcome Measures ......................................................... 46 2.2.2 Remediation ................................................................................................ 47 2.2.3 Compensation ................................................................................................ 50 2.2.4 Holistic .......................................................................................................... 54 2.2.5 Pharmacological Interventions ................................................................. 55 2.2.6 Methylphenidate Hydrochloride ................................................................. 56 2.2.7 Methylphenidate and Attention Deficit Hyperactivity Disorder .................. 56 2.2.8 Methylphenidate and Paediatric Neurooncology ...................................... 58 2.2.9 Paediatric Rehabilitation ........................................................................... 60 2.3 Literature Search of Relevant Studies ................................................................... 61 2.4 Study Selection ........................................................................................................ 61 2.5 Charting the Data ..................................................................................................... 62 2.6 Collating, Summarising and Reporting the Results ...................................... 63 2.7 Optional Consultation ............................................................................................. 63 CHAPTER THREE: METHODOLOGY ................................................................. 64 3.1 Research Design ............……………………………………………..................... 64 3.2 Development of the Study ................................................................................... 65 3.3 Search Strategy for Identification of Studies .................................................... 66 3.3.1 Criteria for Study Inclusion ……...................………………................ 66 3.3.2 Exclusion Criteria …………………………………….............................. 66 3.3.3 Development of Search Strategies …………………....................……. 67 3.4 Searches: Electronic Databases …………....................................………….. 69 3.5 Searches: Hand Searches .....................................................................
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