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Brain Advance Access originally published online on February 2, 2006
Brain 2006 129(4):1040-1049; doi:10.1093/brain/awl021
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© The Author (2006). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Longitudinal MRI in progressive supranuclear palsy and multiple system atrophy: rates and regions of atrophy

Dominic C. Paviour1,2, Shona L. Price2, Marjan Jahanshahi3, Andrew J. Lees1,4 and Nick C. Fox2

1 The Sara Koe PSP Research Centre, Institute of Neurology UCL, 2 Dementia Research Centre (UCL), Institute of Neurology and 3 The Cognitive-Motor Neuroscience Group, Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, 4 Rita Lila Weston Institute of Neurological Studies, UCL, London, UK

Correspondence to: Dr Dominic C. Paviour, The Sara Koe PSP Research Centre, Institute of Neurology, UCL, London UK or Dementia Research Centre (UCL), Institute of Neurology, London, UK E-mail: dpaviour{at}dementia.ion.ucl.ac.uk

The rate of brain atrophy and its relationship to clinical disease progression in progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is not clear. Twenty-four patients with PSP, 11 with MSA-P (Parkinsonian variant), 12 with Parkinson's disease, and 18 healthy control subjects were recruited for serial MRI scans, clinical assessments and formal neuropsychological evaluations in order to measure brain atrophy during life and its association with disease progression in PSP and MSA-P. Serial scans were registered and rates of whole brain atrophy calculated from the brain-boundary shift integral. Regional rates of atrophy were calculated in the brainstem (midbrain and pons), the cerebellum, the lateral and third ventricles as well as frontal and posterior inferior brain regions, by locally registering to a region of interest in order to derive a local boundary shift integral (BSI). 82% of recruited subjects completed serial MRI scans (17 PSP, 9 MSA-P, 9 Parkinson's disease patients and 18 healthy controls). Mean (SD) annualized rates of whole-brain atrophy were greatest in PSP: 1.2% (1.0%), three times that in controls. Mean (SD) midbrain atrophy rates in PSP, 2.2% (1.5%), were seven times greater than in healthy controls. In MSA-P, atrophy rates were greatest in the pons: 4.5% (3.2%), over 20 times that in controls and three times the rate of pontine atrophy in PSP. Atrophy rates in Parkinson's disease were not significantly different from control rates of atrophy. Variability in the atrophy rates was lower when calculated using the BSI rather than manual measurements. Worsening motor deficit was associated with midbrain atrophy in PSP, and ponto-cerebellar atrophy in MSA-P. Worsening executive dysfunction was associated with increased rates of frontal atrophy in PSP. Cerebellar atrophy rates were better discriminators of MSA-P than cross-sectional volumes. We confirm that serial MRI can be applied to measure whole brain and regional atrophy rates in PSP and MSA-P. Regional rather than whole-brain atrophy rates better discriminate PSP and MSA-P from healthy controls. Clinico-radiological associations suggest these regional atrophy rates have potential as markers of disease progression in trials of novel therapies.

Key Words: longitudinal MRI; PSP; MSA-P; Parkinson's disease

Abbreviations: BSI = boundary shift integral; DRS = Mattis dementia rating scale; FAB = frontal assessment battery; MMSE = Mini-Mental State Examination; MSA-P = multiple system atrophy parkinsonian type; PASAT = paced auditory serial addition test; PSP = progressive supranuclear palsy; ROI = region of interest; SCP = superior cerebellar peduncle; UPDRS = Unified Parkinson's disease rating scale; WCST = Wisconsin Card Sorting Test

Received September 17, 2005. Revised January 3, 2006. Accepted January 6, 2006.


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