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Title: Clinical and radiological studies in PSP and related conditions
Author: Massey, L. A.
ISNI:       0000 0004 5363 5827
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2014
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This thesis examines clinical and radiological aspects of Progressive Supranuclear Palsy (PSP) and related conditions. Significant milestones occur sooner in pathologically confirmed PSP than multiple system atrophy (MSA); older age of onset and shorter duration to first milestone are associated with worse prognosis in both; in PSP, the Richardson’s syndrome phenotype and male gender and in MSA, early autonomic failure and the female gender are also predictive of poorer prognosis. Using objective measurements of bradykinesia we found progressive bradykinesia and hypokinesia in Parkinson’s disease (PD) which correlates with disability and responds to levodopa but hypokinesia without decrement in PSP. Using conventional MRI 72.7% of PSP and 76.9% of MSA are correctly identified. The ‘hummingbird sign’ was highly specific for PSP, but sensitvity was 68.4%. A simple measurement of the midbrain < 9.35mm had 100% specificity for a pathological diagnosis of PSP. In a clinically diagnosed PSP 90.5% had a measurement of < 9.35mm. Using high field 9.4 Tesla MRI, the anatomy of the subthalamic nucleus is clearly defined when compared to histology in post mortem material. The anteromedial portion was hypointense in correlation with Perls stain and there was variability in the volume, shape and location of its borders. The nigrosomes within the substantia nigra were visibile as high intensity bands which correlated with calbindin poor zones on immunohistochemical stains. The volume and anatomy were preserved in PD but not PSP. Multimodal 3 Telsla MRI during life revealed distinct patterns of atrophy in PSP and MSA using voxel-based morphometry. Tract-based spatial statistics revealed abnormalities in the frontal and parieto-occipital white matter changes in PSP more than MSA. Midbrain atrophy and frontal white matter increased mean diffusivity were associated with increasing PSP rating scale score, and frontal white matter reduced fractional anisotropy with disease duration.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available