Ipsilateral deficits of dopaminergic neurotransmission in Parkinson's disease

OBJECTIVE The nigral lesion and the resulting contralateral motor signs of Parkinson's disease (PD) are remarkably asymmetric. This study investigated the prevalence of patients with "wrong-sided" lesions, that is, patients with symptoms on the side ipsilateral to the predominant dopaminergic nigrostriatal deficit. METHODS The analyzed sample included 434 early unmedicated PD patients from the Parkinson's Progression Markers Initiative database. Asymmetry indices of motor function and putamen [(123)I]FP-CIT SPECT were calculated from the screening visit data. RESULTS Ipsilateral deficits were unexpectedly common even when only patients with clear motor and dopaminergic asymmetries were included in the analysis (8.1%, n = 24/295). When patients with any asymmetry were included in the analysis, the prevalence of ipsilateral deficits was 15.4% (n = 65/423). Wrong-sided symptoms were not associated with the PD motor subtype. However, the dataset was heavily biased toward tremor-dominant patients (85% of patients). Right-handed PD patients had predominantly right-sided motor symptoms and left-sided dopamine defects, whereas the effect was opposite in left-handed patients (P = 0.005 and 0.028, respectively). INTERPRETATION The results indicate that the side of the predominant motor symptoms and the corresponding side of the dopaminergic defects in PD are not random, but are directed by brain lateralization. Importantly, the traditional pathogenetic model of nigral degeneration causing primarily contralateral motor symptoms may be inadequate in many patients.