Striatal Hypertrophy: A Mechanism for Preclinical Compensation in Parkin-Associated Parkinsonism?

¹⁸F-Fluorodopa (F-DOPA) positron emission tomography (PET) demonstrated a reduction of striatal F-DOPA uptake in asymptomatic carriers of heterozygous Parkin mutations, indicating a latent dopaminergic dysfunction in the basal ganglia. We used voxel-based morphometry of high-resolution structural magnetic resonance images in a comparable group of asymptomatic Parkin mutation carriers to investigate whether this latent dopaminergic dysfunction is associated with structural abnormalities in the motor system. Structural MR data (T₁-weighted FLASH 3D MR sequences; TE=5 ms; TR=15 ms; flip angle=30°; isotropic voxel size 1×1 x 1mm³) of 13 right handed asymptomatic carriers of heterozygous mutations in the Parkin gene (eight females, mean age: 38.6±5.8yrs, range: 28–47yrs) were compared with those of 13 age-matched healthy controls. MR images were preprocessed and analyzed using SPM2 software (FIL, London, UK). We used an optimized protocol for voxel-based morphometry, which involves non-linear spatial normalization to a customized grey matter template. Images were smoothed with a Gaussian kernel 12mm FWHM. Using a general linear model, voxel-by-voxel t-tests were computed to detect differences in grey matter volume between groups (significance threshold: p<0.01 and p<0.01 for cluster size; Gaussian Random Field theory). All asymptomatic carriers and controls had a normal neurological and neuropsychological examination. Voxel-based morphometry revealed a significant increase in grey matter volume in the left posterior putamen and globus pallidus internus (GPI) [Talairach coordinates: x=–25, y=0, z=3; SVC around the striatum p=0.03, corrected (FDR)]. There was also a subthreshold increase in grey matter volume in the right GPI. The increase in grey matter volume in the posterior striatum showed a close spatial correspondence to the location of dopamine hypometabolism found in the comparable group of asymptomatic carriers in the previous F-DOPA PET study (Hilker et al., 2001). This co-localization may suggest that the increase in grey matter volume might represent a long-term consequence of adaptive plasticity in the basal ganglia. Such an increase in structure might help the motor system to compensate for the preclinical dopaminergic deficit and prevent the manifestation of minor motor symptoms (Brezard et al., 2003). The higher increase in the grey mater density in the left striatum indicates a higher amount of compensation for the dominant right hand.