Mechanisms underlying and medical management of l-Dopa-associated motor complications

Abstract

Springer-Verlag 2011 Motor complications, particularly motor fluctuations such as wearing-off, on-off phenomena, and several different types of dyskinesia such as peak-dose, diphasic, wearing- off, chorea, dystonia and athetosis (collectively called dyskinesia) seem to be an inevitable consequence of L-Dopa (L-3,4-dihydroxyphenylalanine, levodopa) therapy of patients suffering from Parkinson's Disease (Jankovic 2005 ;M uller and Russ 2006). However, not all patients develop dyskinesia even after long periods of treatment suggesting that specific deteriorations or adaptations occur in one group of patients but not in the other. The present understanding of the underlying mechanisms of those dif- ferences is far from being known. The stage of the illness (degree of dopaminergic degeneration and loss of nigro- striatal projections) as well as the dose and frequency of L-Dopa treatment have been considered as essential con- tributors to the induction and expression of the involuntary movements. Age of the patients at onset of the symptoms and the speed of progression are further aspects. The statement by Iravani and Jenner (2011, this issue), ''the cause of L-Dopa-induced dyskinesia remains to be fully elucidated'', seems to suggest that we are indeed only at the beginning of the understanding of the mechanisms. The knowledge on pre- and post-synaptic events and their contribution to dyskinesia as well as the role of the dopa-