Kawadler, JM; (2015) Neuroimaging Biomarkers in Paediatric Sickle Cell Disease. Doctoral thesis , UCL (University College London).

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Abstract

Sickle Cell Disease (SCD) is a collection of genetic haemoglobinopathies, the most common and severe being homozygous sickle cell anaemia. In the UK, it has been estimated that 1 in 2000 children are born with SCD. The disease is characterised by chronic anaemia, recurrent pain crises and vascular occlusion. Neurologically, there is a high incidence of stroke in childhood, as well as cognitive dysfunction. Newborn screening programmes and preventative treatments have allowed a much longer lifespan; however recently, neurological research has shifted to characterising subtler aspects of brain development and functioning that may be critically important to the individual’s quality of life. This thesis overviews the neurological and neurocognitive complications of SCD, and how magnetic resonance imaging (MRI) can provide biomarkers for severity of disease. During the PhD, retrospective and prospective cognitive and MRI data were collected and analysed. Diagnostic clinical MRI sequences and advanced MRI sequences were applied, as well as a neuropsychological test battery aimed at intelligence and executive function. First, this thesis reviews the intelligence literature in SCD and includes previously unreported data, finding patients, regardless of abnormality seen on conventional MRI, have lowered full-scale intelligence quotient than controls. Then, to determine imaging biomarkers, volumetric differences and diffusion characteristics were identified. Patients were found to have decreased volumes of subcortical structures compared to controls, in groups corresponding to disease severity. Results from a three-year longitudinal clinical trial suggest evidence of atrophy in paediatric patients, with no apparent protective effect of treatment. Diffusion tensor imaging revealed reduced white matter integrity across the brain, correlating with recognised markers of disease severity (i.e. oxygen saturation and haemoglobin from a full blood count). Overall, the four experiments bridge a gap in the cognitive and neuroimaging literature of the extent of neurological injury in children with SCD.

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