Left hemispheric predominance of nigrostriatal dysfunction in Parkinson's disease.

Abstract

The aim of this study was to investigate the distribution and the degree of asymmetric putaminal dopamine transporter availability in right-handed patients with Parkinson's disease and its association with the severity of lateralized motor signs. Asymmetry of motor symptoms was defined by the difference between right- and left-sided scores for lateralized items assessed by the Unified Parkinson's Disease Rating Scale Motor Score in a series of 68 patients with Parkinson's disease (disease duration 2.1 ± 1.5 years; Unified Parkinson's Disease Rating Scale Motor Score 22.7 ± 9). Putaminal dopamine transporter availability was measured with the radioligand [(123)I]β-carboxymethyoxy-3 -β-(4-iodophenyl) tropane ([(123)I]β-CIT) and single photon emission computed tomography. We found that in the right-handed Parkinson's disease cohort, the number of patients who had lower dopamine transporter uptake in the left posterior putamen was significantly greater compared with those with lower uptake in the right posterior putamen (Parkinson's disease-left group, n = 49; Parkinson's disease-right group, n = 19; P < 0.001). In addition, one-way analysis of variance revealed significant reductions of mean total putaminal [(123)I]β-CIT binding of the Parkinson's disease-right patients compared with Parkinson's disease-left patients (P < 0.05).The preponderance of reduced left putaminal dopamine transporter availability strengthens clinical observations of a greater proportion of right-handed patients with Parkinson's disease with predominantly right-sided motor signs and argues against a randomly distributed asymmetric vulnerability of substantia nigra dopaminergic neurons. The coexistence of a subgroup of right-handed patients with Parkinson's disease with more severe and predominant ipsilateral putaminal dopamine transporter decline suggests that asymmetry of dopaminergic denervation and motor dysfunction in Parkinson's disease cannot be fully explained by hemispheric dominance alone, but that other factors must be involved.