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Brain Advance Access originally published online on June 24, 2007
Brain 2007 130(8):2123-2128; doi:10.1093/brain/awm142
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© The Author (2007). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Patterns of levodopa response in Parkinson's disease: a clinico-pathological study

P. A. Kempster1,2, D. R. Williams1,3, M. Selikhova1, J. Holton1, T. Revesz1 and A. J. Lees1

1Queen Square Brain Bank for Neurological Disorders and Institute of Neurology, University College, London, UK, 2Neurosciences Department, Monash Medical Centre and 3Faculty of Medicine (Neuroscience), Monash University (Alfred Hospital Campus), Melbourne, Australia

Correspondence to: Prof A.J. Lees, Reta Lila Weston Institute of Neurological Studies, 1 Wakefield Street, London, WC1N 1PJ, UK E-mail: alees{at}ion.ucl.ac.uk

Patients with Parkinson's disease who develop disabling levodopa-induced motor fluctuations have a stronger therapeutic response than those who experience a more modest but stable response. A difference in the histopathological lesion between the two groups might be responsible. Case records from 97 patients with pathologically proven Parkinson's disease were reviewed to determine the pattern of levodopa response. Pathological findings for fluctuating and non-fluctuating cases were compared. Patients with motor fluctuations had a younger age of onset and longer disease course (P < 0.001), although mean age at death was almost the same. Four milestones of advanced disease (frequent falls, visual hallucinations, cognitive disability and need for residential care) occurred at a similar time from death in each group; this interval was not proportionate to the disease duration. There were no significant differences in the severity or distribution of Lewy body or other pathologies. Irrespective of the pattern of levodopa response, patients reach a common pathological endpoint at a similar age, and the duration and manifestations of end-stage disease are alike. A non-linear or exponential time relationship may govern the late clinical and pathological progression of Parkinson's disease.

Key Words: Parkinson's disease; motor fluctuations; Lewy body

Abbreviations: LB, Lewy body

Received February 19, 2007. Revised May 22, 2007. Accepted May 25, 2007.


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