Regional metabolism in primary torsion dystonia - Effects of penetrance and genotype

Background: The authors have previously used [F-18]fluorodeoxyglucose (FDG) PET to identify a reproducible pattern of regional glucose metabolism that was expressed in both manifesting and nonmanifesting carriers of the DYT1 primary dystonia mutation. Objective: To identify specific regions that discriminated subjects according to clinical penetrance and genotype. Methods: FDG PET was used to scan 12 nonmanifesting and 11 manifesting DYT1 gene carriers, 6 nonmanifesting DYT6 gene carriers and 7 manifesting DYT6 gene carriers, as well as 11 control subjects. The data from all five groups were analyzed with statistical parametric mapping and analysis of variance with posthoc contrasts. Results: A dissociation of metabolic changes was found related to phenotype and genotype. Manifesting gene carriers of both genotypes exhibited bilateral hypermetabolism in the presupplementary motor area (Brodmann area [BA] 6) and parietal association cortices (BA 40/7) compared with the respective nonmanifesting counterparts. By contrast, genotype-specific increases in metabolism were found in the putamen, anterior cingulate (BA 24/32), and cerebellar hemispheres of DYT1 carriers. Genotype-specific changes in DYT6 involved hypometabolism of the putamen and hypermetabolism in the temporal cortex (BA 21). Conclusions: Dystonia may be associated with abnormal movement preparation caused by defective sensorimotor integration. Whereas clinical manifestations are related to cortical dysfunction, metabolic abnormalities in subcortical structures may represent trait features that are specific for individual dystonia genotypes.