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
