Dopaminergic Dysfunction and Glucose Metabolism Characteristics in Parkin-Induced Early-Onset Parkinson's Disease Compared to Genetically Undetermined Early-Onset Parkinson's Disease.

UNLABELLED

While early-onset Parkinson's disease (EOPD) caused by mutations in the parkin gene () tends to have a relatively benign course compared to genetically undetermined (GU)-EOPD, the exact underlying mechanisms remain elusive. We aimed to search for the differences between -EOPD and GU-EOPD by dopamine transporter (DAT) and glucose metabolism positron-emission-tomography (PET) imaging. Twelve patients with -EOPD and 16 with GU-EOPD who accepted both C-2b-carbomethoxy-3b-(4-trimethylstannylphenyl) tropane (C-CFT) and F-fluorodeoxyglucose PET were enrolled. The C-CFT uptake was analyzed on both regional and voxel levels, whereas glucose metabolism was assessed in a voxel-wise fashion. Correlations between DAT and glucose metabolism imaging, DAT imaging and clinical severity, as well as glucose metabolism imaging and clinical severity were explored. Both clinical symptoms and DAT-binding patterns in the posterior putamen were highly symmetrical in patients with -EOPD, and dopaminergic dysfunction in the ipsilateral putamen was severer in patients with -EOPD than GU-EOPD. Meanwhile, the DAT binding was associated with the severity of motor dysfunction in  patients with GU-EOPD only. Patients with -EOPD showed increased glucose metabolism in the contralateral medial frontal gyrus (supplementary motor area (SMA)), contralateral substantia nigra, contralateral thalamus, and contralateral cerebellum. Notably, glucose metabolic activity in the contralateral medial frontal gyrus was inversely associated with regional DAT binding in the bilateral putamen. Patients with -EOPD showed enhanced metabolic connectivity within the bilateral putamen, ipsilateral paracentral and precentral lobules, and the ipsilateral SMA. Collectively, compared to GU-EOPD, -EOPD is characterized by symmetrical, more severe dopaminergic dysfunction and relative increased glucose metabolism. Meanwhile, SMA with elevated glucose metabolism and enhanced connectivity may act as compensatory mechanisms in -EOPD.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s43657-022-00077-8.