The natural history of parkinson’s disease

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder associated with neuronal loss of the dopaminergic neurons of the substantia nigra (SN) pars compacta [1], but extranigral pathology of the cholinergic, noradrenergic and serotonergic systems have also been well documented [1-3]. At the onset of motor signs in PD, it has been estimated that about two-thirds of cell loss in the lateral ventral tier of the SN pars compacta (SNc) has already occurred [4], and the occurrence of a presymptomatic phase of 5 years is also suggested according to the curve of cell loss in the SN [4, 5]. Clinically, cardinal manifestations of PD are characterised by the presence of asymmetric or even unilateral bradykinesia, rest tremor and rigidity, and postural instability later in the disease course [6, 7]. Classically, the natural history of PD has been regarded as the progression in severity of motor symptoms and the emergence of levodopa-induced motor complications (MC) [6]; however, non-motor symptoms (NMS) of PD, such as dementia, depression, psychosis or dysautonomia, are now well accepted as important features of PD, and they have changed the way we regard the natural history of PD [8-10].