The mystery of motor asymmetry in Parkinson's disease

The motor symptoms of Parkinson's disease are predominantly due to progressive degeneration of nigral dopaminergic neurons. In most cases there is a substantial asymmetry of clinical symptoms from disease onset, which occurs in sporadic and in hereditary forms of the disease. However, the mechanism of such unilaterality of symptom appearance is not understood. There is only sparse information about whether symptom-side predominance is genetically coded and determined years before symptom onset, or whether it is acquired and related to side differences in vulnerability of the degenerating neurons. In this Personal View we review data for unilaterality of symptoms at different disease stages. We also discuss several pathological, genetic, environmental, and toxic possibilities for explaining the mechanism of side predominance.