Siddique, D-E-N; (2008) Investigation of the brain magnetisation transfer ratio, cognitive and neurological measures in prion disease. Doctoral thesis , UCL (University College London).

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Abstract

The work described in this thesis examines the application of magnetisation transfer ratio (MTR) measurement, a quantitative magnetic resonance imaging (MRI) technique, in evaluating patients with different forms of human prion disease. In particular whether MTR changes can be shown: 1. to correlate with clinical disease severity and disease type 2. to evolve on serial MRIs in clinically progressive disease 26 patients were assessed over 3 years. Global and regional cerebral MTRs were calculated using validated software and regions of interest manually defined on MTR maps. Whole brain, grey matter and white matter MTR histograms were computed and mean, peak height, peak location, and 25th, 50th and 75th percentile MTR histogram values were calculated to demonstrate localised and subtle diffuse pathological changes. A blinded assessment of DWI/FLAIR images was performed to determine MTR changes in areas with or without signal change on conventional MRI. Patients were assessed using clinical video scores and neurological scales: Clinician's Global Impression of Disease Severity, Clinician's Dementia Rating, Alzheimer's disease Assessment Scale, Activities of Daily Living, Brief Psychiatric Rating Scale, Mini Mental Score Examination, Glasgow Coma Score and Rankin scores. Temporal changes in these tests of cognition, functional abilities, psychiatric symptoms and conscious state are described. Spearman rank correlation and linear regression analyses were performed. At baseline, lower whole brain and grey matter MTR histogram parameters correlated significantly with lower cognitive, extrapyramidal and cerebellar impairment, as well as with MMSE, CDR, ADAS-COG, CGIS and Rankin scores. Longitudinal decline in multiple whole brain, white matter and grey matter MTR histogram parameters was associated with progressive extrapyramidal and CDR impairment. Four patients at baseline and 2 patients longitudinally had conventional MRI abnormalities. Decreased MTR may be used as a biomarker of disease severity and is a potential outcome measure in future therapeutic trials in prion disease.

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