Does the side of onset influence symptom severity in Parkinson's disease? A systematic review and meta-analysis

Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by motor symptoms that initially manifest unilaterally. Whilst some studies indicate that right-side onset is associated with greater symptom severity, others report no differences between right-side and left-side onset patients. The present meta-analysis was thus designed to reconcile inconsistencies in the literature and determine whether side of onset affects PD symptom severity. Following the PRISMA guidelines 1013 studies were initially identified in database and grey literature searches; following title and abstract, and full text, screening 34 studies met the stringent inclusion criteria (n = 2210). Results of the random-effects meta-analysis indicated no difference in symptom severity between PD patients with left-side (n = 1104) and right-side (n = 1106) onset. As such, the meta-analysis suggests that the side of onset should not be used to predict symptom trajectory or to formulate prognoses for PD patients. The current meta-analysis was the first to focus on the relationship between the side of onset and symptom severity in PD. However, the studies included were limited by the common exclusion of left-handed participants. Future research would benefit from exploring other factors that may influence symptom severity and disease progression in PD, such as asymmetric loss of nigrostriatal dopaminergic neurons.