New ideas on the origin of l-dopa-induced dyskinesias: age, genes and neural plasticity

Abstract

More than 50% of Parkinson's disease (PD) patients treated with L-dopa develop L-dopa-induced dyskinesias (LIDs) in the long term. Some patients exhibit severe dyskinesias soon after starting low doses of L-dopa, whereas other patients remain free of this disabling complication despite treatment with L-dopa. Avoiding or delaying the appearance of LIDs is one of the main objectives of the management of PD. Plasticity of the brain to adapt to a progressive disease, together with a non-physiological treatment strategy, might be the key physiopathological element that underlies LIDs. Neural plasticity varies among patients according to age and genetics. Thus, I propose that this variation explains the observed differences in the occurrence of LIDs in PD patients. Furthermore, I suggest that denervation and L-dopa treatment act as modulating and triggering factors of LIDs, respectively. In this article, the practical implications of these ideas and the role of pharmacogenetics in PD treatment are discussed. Treatment decisions are likely to rely on this information, challenging the relevance of current 'hot' debates about how to start treatment in PD.