Abstract
A bilateral compensatory increase of basal ganglia (BG) gray matter value (GMV) was recently demonstrated in asymptomatic Parkin mutation carriers, who likely have an increased risk to develop Parkinson's disease (PD). We hypothesized BG morphological changes in symptomatic Parkin mutation carriers (s__PARKIN__‐MC) and idiopathic PD patients (iPD) after the occurrence of PD symptoms, reflecting the breakdown of compensatory mechanisms. Nine s__PARKIN__‐MC, 14 iPD, and 24 controls were studied clinically and with voxel‐based morphometry. Analysis of variance revealed mainly BG decrease of GMV in s__PARKIN__‐MC and to a lesser extent in iPD. However, a slight increase in GMV was also found in the right globus pallidus externus in s__PARKIN__‐MC and in the right putamen in iPD. This may reflect a structural correlate of functional compensation that can only partially be maintained when nigrostriatal neurodegeneration becomes manifest. Simple regression analyses with the UPDRS‐III and disease duration score revealed a distinct more bilateral linear decrease of BG GMV in s__PARKIN__‐MC than in iPD that may correspond to previous findings showing a symmetric reduction in putaminal ^18^F‐DOPA‐uptake and bilateral manifestation of symptoms in s__PARKIN__‐MC. In symptomatic PD, BG are subject to a progressive atrophy, which gradually increases with disease severity and duration. © 2008 Movement Disorder Society