Persistence of the striatal hypertrophy at the symptomatic stage of genetically determined and idiopathic parkinsonism

Objectives: An increase in gray matter volume in the striatum has been proposed as a mechanism of presymptomatic compensation in asymptomatic heterozygous Parkin- and PINK1- gene mutation carriers (Binkofski et al., 2004). In the present study we investigated changes of basal ganglia (BG) volumes in symptomatic carriers of Parkin gene mutation and in patients with idiopathic Parkinson's disease (iPD) using voxel-based morphometry (VBM). In particular, we determined whether the increase in striatal volume is still present in patients with parkinsonism and whether it depends on the severity of symptoms.

Methods: We compared structural MR images (T1-weighted 3D MPRAGE) of 10 symptomatic carriers of mutations in the Parkin gene and 14 iPD patients with 24 age- and sex-matched controls. MR images were analyzed with the optimized VBM protocol (Good et al., 2001) and SPM2 (Wellcome Department of Cognitive Neurology, London, UK). One-way ANOVA was used to calculate contrasts between the gray matter images of the four groups. Based on our hypothesis, we investigated the basal ganglia volumes using a mask from the WFU-pickatlas (Wake Forest University, USA) at an uncorrected threshold of p<0.01.

Results: An increase in gray matter volume was found in the right putamen in the symptomatic Parkin mutation carriers and iPD patients in comparison to the matched controls. Simple regression analysis revealed a negative correlation between the BG gray matter values and the UPDRSIII score as well as the duration of disease in both patient groups. In addition, there was a decrease of gray matter volume in the left caudate in the symptomatic Parkin mutation carriers.

Conclusion: We conclude that the presence of the striatal hypertrophy at the symptomatic stage of PD indicates the persistence of this putative compensatory mechanism in PD patients as proposed previously in a VBM study on asymptomatic heterozygous Parkin mutation carriers (Binkofski et al., 2004). The negative correlation of the striatal gray matter volume with the clinical scores suggests that this compensation mechanism is waning with the duration and severity of the disease.