L-dopa-Induced Dyskinesias in Parkinson's Disease

REVIEW ARTICLE


Iciar Aviles-Olmos*, Raul Martinez-Fernandez*, and Thomas Foltynie

Affiliation: Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London,United Kingdom

ABSTRACT

Levodopa (L-dopa) is the most effective treatment for the relief of the motor symptoms of Parkinson's disease (PD). Its use is limited by the development of drug-induced involuntary movements known as dyskinesias, which can appear in approximately 40% of the PD patients after 5 years of treatment. In recent years we have learned a great deal about the processes involved in the appearance of L-dopa-induced dyskinesia (LID). Non-physiological pulsatile stimulation of dopamine receptors that occurs as a consequence of the use of short-lasting drugs, dysfunctional dopamine release, and abnormal postsynaptic dopamine receptor internalization together with disrupted synaptic plasticity all appear to have direct effects on LID development. Avoiding or delaying dyskinesia development and treating patients in this “advanced” stage of PD is a challenge and requires considerable expertise and individualization of therapy. The aim of this review is to outline the clinical phenomenology of LID, describe an overview of what is known about their pathophysiology, and provide guidance in the range of therapeutic approaches that can be tailored to the individual patient.

Keywords: levodopa-induced dyskinesia (LID), Parkinson’s disease (PD), synaptic plasticity, dysfunctional dopamine release, dopamine receptor supersensitivity

Correspondence: Iciar Aviles-Olmos, Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement
Disorders, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, United Kingdom. Tel: +44-08451555000 Ext. 18739; e-mail:
i.olmos@ion.ucl.ac.uk