Biologic rhythms and Parkinson's disease: a chronopharmacologic approach to considering fluctuations in function

The existence of circadian rhythms and their implication in many pathologic processes have been underlined in several diseases but have not been evaluated in Parkinson's disease. The aim of this paper is to review diurnal variations of clinical, biologic, or experimental factors described with Parkinson's disease. Clinical data often report daily fluctuations of motor activity pattern, but the effect of the stage of the disease and the respective roles of drugs are difficult to evaluate. Sleep disturbances in Parkinson's disease patients also reveal alterations of circadian rhythms. Autonomic dysfunction, described in Parkinson's disease, reveals numerous alterations in circadian regulations including loss of circadian rhythm of blood pressure, increased diurnal blood pressure variability, and postprandial hypotension. Many biologic indices such as cortisol, catecholamines, and melatonin are also altered. Circadian rhythms in dopaminergic systems as well as possible daily fluctuations in kinetics of drug treatments are likely involved in such variations. Few clinical studies have been devoted to circadian patterns of drug response. As for other diseases where biologic rhythms are concerned Parkinson's disease therapy may be influenced by further understanding of circadian influence.