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Dizziness and balance difficulties are not uncommon in children, with prevalence estimates in the general population ranging from 5%-18%, although the precise prevalence of those caused by vestibular dysfunction is not known. Whilst healthcare professionals are aware that vestibular dysfunction may lead to poor balance and delayed gross motor development in young children, little is known generally about the longer-term consequences of vestibular dysfunction in this group. This thesis sought to identify the existing evidence in the literature regarding the impact of vestibular dysfunction in children and young people (CYP), to identify the evidence gaps, and to add to the existing knowledge base by reporting on the author's own original research study regarding chronic symptoms and health-related quality of life in this group. The thesis includes a scoping review of the literature performed to identify and summarize evidence from studies investigating the impact of vestibular dysfunction in CYP (e.g. ongoing symptoms, balance function, motor development and health-related quality of life). Databases and other sources were searched methodically and 33 studies met the criteria for inclusion in the review. The review confirmed that there is some evidence about the physical effects of vestibular dysfunction in children, but that this evidence is limited by methodological and design quality issues and the heterogeneous nature of the studies. There is a paucity of evidence about the interaction between vestibular and cognitive function, and the impact on psychological wellbeing and quality of life in CYP with vestibular dysfunction, The empirical research paper, presented in a journal paper format, reports on the author's own observational cohort study of CYP with vestibular dysfunction. For this study, 49 CYP with vestibular dysfunction and 44 of their parents/carers completed a survey which included the Paediatric Vestibular Symptom Questionnaire (pVSQ), the Paediatric Quality of Life Inventory (PedsQL) and an open question asking for comments about vestibular dysfunction affects their/their child's life. The findings indicate that chronic vestibular symptoms are ongoing in many CYP with vestibular dysfunction even years after the onset of vestibular dysfunction: the majority of CYP (76%) in this study and most of the parents and carers (81%) reported the presence of significant levels of vestibular symptoms (the mean duration since onset of was 7.9 years), with females reporting more severe symptoms than males. Vestibular dysfunction was associated with impaired health-related quality of life (HRQoL): 61% of the children and young people in this study, and 57% of their parent/carers reported significantly impaired HRQoL in all domains compared to healthy norms. Linear regression modelling confirmed that high levels of vestibular symptoms are the main predictor of poor HRQoL with congenital vestibular dysfunction, and bilateral or central vestibular dysfunction also being additional risk factors for reduced HRQoL. Thematic analysis of the qualitative data collected explored study participants' perceptions of the consequences of vestibular dysfunction. Overarching themes identified were ongoing 'Symptoms' and 'Falls & Imbalance', which affected activities such as 'School', 'Exercise', 'Everyday activity', and had an impact on 'Emotions'. The final chapter of the thesis provides a critical review of the process and findings of the scoping review and research study, and the implications of the findings for clinical practice and future research. There is also a reflective account of the author's experience conducting the research as part of the Higher Specialist Scientist Training programme (HSST), and how this has contributed to personal and professional development.

Thesis Abstract An Investigation of Cognitive Deficits Related to Surgery for Glioblastoma using a Computerised Assessment Tool - Rohitashwa Sinha Glioblastoma, the most aggressive type of primary brain cancer, causes abysmal survival rates and high risks of cognitive deficit to its sufferers. These deficits are due to both its being diffusely infiltrative and its radical treatments such as brain surgery and radiotherapy. Currently the course of cognitive deficits from before to after surgery has not been reliably researched. Studies report high rates of drop-out due to burdensome 'pen-and-paper' based assessments conducted by neuropsychologists, a lack of these resources entirely or the data collection being focused on the period around radiotherapy or less aggressive tumours instead. As a result, patients still undergo resection surgery for glioblastoma without a reliable evidence base for making their treatment decisions, without any assessment for their cognitive deficit burden and without any targeted interventions to protect their cognitive function. In this doctoral research, I have set up a prospective study to assess cognitive function before and after resection surgery, but before radiotherapy and with particular focus on participants with glioblastoma who have been underserved by current infrastructure and research focus. The methodology involves using a computerised testing battery called 'OCS-Bridge', which has broadened the access to such cognitive assessments. Participant retention has been higher than in the literature. This may be due in part to the efficiency of the format as well as the study design for data collection, where assessment timepoints were advised by patients and carers rather than clinicians. Using a variety of analysis techniques, this thesis progresses through a systematic review confirming the lack of reliable consensus in this area and a format comparison study to support the use of OCS-Bridge by comparison to conventional testing. Next, machine learning and Kaplan-Meier analyses are used to show cognitive deficits as predictors of clinical outcomes including overall survival. The longitudinal analyses of the high peri-operative odds of cognitive deficits until radiotherapy follows. Finally, a tract based spatial statistics study using diffusion tensor MRI brain scans demonstrates that a common anatomical mechanism exists, affecting the same right hemisphere white matter tracts underlying social cognition deficits in participants with glioblastoma as is seen in traumatic brain injury and neurodegenerative disease contexts. 3 By contributing new knowledge, research methodology, immediately translational implications for clinical practice and by linking the mechanisms of cognitive deficits between glioblastoma and other neurological diseases, the results herein have already secured further research funding. This future work will build on the understanding of cognitive deficits presented here and to trial a targeted rehabilitation intervention to help people with glioblastoma and their families.