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Title: Exploring the phenotypes of individuals with midline brain defects
Author: Webb, E. A.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2014
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Background The prevalence, aetiology and optimal management of the behavioural and cognitive difficulties, and circadian rhythm disturbances in children with midline brain abnormalities including isolated growth hormone deficiency (IGHD), isolated optic nerve hypoplasia (ONH) and septo-optic dysplasia (SOD) have to date not been adequately addressed. Aims and Methods This thesis aims to assess the prevalence of cognitive/behavioural problems and circadian rhythm abnormalities in children with midline brain abnormalities, and to further investigate any problems identified using high resolution MRI brain, actigraphy and melatonin profiling. Results Children with IGHD have significant impairments in motor skills and lower cognitive function scores, and children with ONH have significantly higher scores on the child behavioural checklist than controls. Children with SOD have significant sleep abnormalities. In IGHD corticospinal tract and corpus callosum fractional anisotropy (FA) and specific neural volumes are significantly lower than in controls, with neural abnormalities correlating significantly with IQ and motor skills scores. In ONH ventral cingulum, corpus callosum and optic radiation FA are significantly reduced, with right ventral 13 cingulum FA correlating significantly with behavioural assessment scores. In SOD melatonin production was absent in one child in association with a fragmented sleep pattern. Three children had normal melatonin profiles, one with an arrhythmic and two with fragmented sleep patterns. The remaining child had fragmented sleep and a modest increase in daytime melatonin concentrations. Conclusions These studies suggest that the GH-IGF-1 axis plays a role in brain and cognitive development. They also show that children with ONH require behavioural assessment, not previously part of routine clinical care, and that the behavioural abnormalities identified in children with ONH may be related to underlying whiter matter abnormalities. We have also demonstrated that the aetiology of the sleep disturbances found in SOD is complex, and not solely due to abnormal nocturnal melatonin production.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available