Patterns of asymmetry do not change over the course of idiopathic parkinsonism: implications for pathogenesis

We investigated the asymmetry of focal deficits of bradykinesia in a cross-sectional study of 198 patients with idiopathic parkinsonism. We have analyzed the difference in Unified Parkinson's Disease Rating Scale (UPDRS) scores between the more and less affected sides in these patients, whose duration of symptoms ranged from 1 to 15 years. There was no significant change in the asymmetry or focality over this period; the deficit for each side progressed faster initially and then approached the normal age-related linear rate of decline. Previous studies indicate that there is an inverse linear relation between the UPDRS bradykinesia score and the nigral dopaminergic cell count. We infer that the rate of death of nigral dopaminergic neurons is predetermined from the time of onset of pathogenesis. The simplest explanation is that a causal event kills some cells and damages others so that they undergo premature death. This sequence of changes could be implemented through environmental (toxic or viral) damage to the genome. Several diverse sources of evidence support this concept.