The L-dopa response in Parkinson's disease

Pitz, Vanessa (2021) The L-dopa response in Parkinson's disease. PhD thesis, University of Glasgow.

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Abstract

L-dopa is the most commonly prescribed drug for the treatment of Parkinson’s disease (PD). Most patients benefit from this treatment as it can restore motor function but over time, a large proportion of patients report the manifestation of side effects. The L-dopa response is also a supportive criterion for the diagnosis of PD.
This thesis aimed to explore the variation of responsiveness to L-dopa and to identify predictor variables for responsiveness. This was achieved by systematically reviewing pathological studies and case reports; analysing two large and longitudinal clinical cohort studies with focus on short- and long-term indicators of responsiveness; and the analysis of brain imaging data indicative of the degree of dopaminergic loss at different stages of the disease.
The systematic review established a great variation in responsiveness to L-dopa, analysing pathologically confirmed cases where there is little to no doubt about diagnostic accuracy: 10% of definite Parkinson’s are unresponsive to L-dopa and 12% show a modest response. The clinical cohort analysis showed that current treatment management approaches lead to an overall lower prevalence of motor complications compared to earlier studies, even when L-dopa is introduced early-on. Motor fluctuations have the greatest impact on motor function but also on the patients’ abilities in everyday life situations. Investigating the short-term response showed an association of better motor function with the development of dyskinesia, and dyskinetic patients with a better response to challenge testing. Finally, SPECT imaging data showed a high residual activity of dopamine in early PD, and an association of lower putaminal uptake with higher medication doses at later stages of the disease.
In conclusion, a lesser response to L-dopa should be considered as a definite phenomenon in a large proportion of PD patients. Assessing L-dopa responsiveness more widely, in clinical practice and clinical research would enhance both our understanding of patients and our interpretation of the effects of new drug treatments.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Parkinsons, Levodopa, UPDRS, SPECT.
Subjects: R Medicine > R Medicine (General)
R Medicine > RM Therapeutics. Pharmacology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Funder's Name: Parkinson`s UK (PARKINSO)
Supervisor's Name: Tobias, Prof. Dr. Edward and Grosset, Dr. Donald
Date of Award: 2021
Depositing User: Dr Vanessa Pitz
Unique ID: glathesis:2021-82151
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 29 Apr 2021 07:46
Last Modified: 29 Apr 2021 07:51
Thesis DOI: 10.5525/gla.thesis.82151
URI: http://theses.gla.ac.uk/id/eprint/82151
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