An 18-fluorodeoxyglucose-PET study in SGCE positive and negative myoclonus-dystonia

Myoclonus-dystonia is a hyperkinetic movement disorder, and approximately half of myoclonus-dystonia patients have a mutation in the epsilon-sarcoglycan (SGCE) gene, while the remaining cases often have undetermined causative genes. This study aims to assess brain metabolic function in myoclonus-dystonia patients with and without SGCE mutations and compare them with a control group. This study is part of the Next Move in Movement Disorders observational study. We included 23 myoclonus-dystonia patients (11 with SGCE mutations and 12 without) and 23 age-matched controls. Participants underwent 18-fluordeoxyglucose-PET and anatomical MRI scans. Data were analysed using a voxel-based analysis and a volume of interest (VOI)-based analysis. In the voxel-based analyses, trends towards differences in the supplementary motor area, cingulate gyrus, parietal and occipital lobe were found. When comparing mutation-positive with mutation-negative patients, trends towards differences in the parietal lobe and pre-central gyrus were detected. Symptom severity was correlated with changed metabolism in post-central and supramarginal gyrus, occipital and frontal lobe, cerebellum and caudate nucleus. In addition, VOI-based analyses showed statistically significant differences in the supplementary motor area comparing myoclonus-dystonia patients with controls. The identified trends of increased metabolism in the (pre)motor cortex areas fit the model of a more 'excitable' state with a lower activation threshold, possibly due to reduced inhibition from the cerebellum and striatum, regions in which we found a negative correlation between symptom severity and metabolism. Differences were also observed in sensory areas such as the parietal lobe and visual cortex. While the phenotype of SGCE mutation-positive and mutation-negative groups is similar, subtle differences suggest distinct endophenotypes.