title: Metabolic changes in DYT11 myoclonus-dystonia.
abstract: OBJECTIVE
  To identify brain regions with metabolic changes in DYT11 myoclonus-dystonia (DYT11-MD) relative to control subjects and to compare metabolic abnormalities in DYT11-MD with those found in other forms of hereditary dystonia and in posthypoxic myoclonus.
  
  
  METHODS
  [(18)F]-fluorodeoxyglucose PET was performed in 6 subjects with DYT11-MD (age 30.5 ± 10.1 years) and in 6 nonmanifesting DYT11 mutation carriers (NM-DYT11; age 59.1 ± 8.9 years) representing the parental generation of the affected individuals. These data were compared to scan data from age-matched healthy control subjects using voxel-based whole brain searches and group differences were considered significant at p < 0.05 (corrected, statistical parametric mapping). As a secondary analysis, overlapping abnormalities were identified by comparisons to hereditary dystonias (DYT1, DYT6, dopa-responsive dystonia) and to posthypoxic myoclonus.
  
  
  RESULTS
  We found significant DYT11 genotype-specific metabolic increases in the inferior pons and in the posterior thalamus as well as reductions in the ventromedial prefrontal cortex. Significant phenotype-related increases were present in the parasagittal cerebellum. This latter abnormality was shared with posthypoxic myoclonus, but not with other forms of dystonia. By contrast, all dystonia cohorts exhibited significant metabolic increases in the superior parietal lobule.
  
  
  CONCLUSIONS
  The findings are consistent with a subcortical myoclonus generator in DYT11-MD, likely involving the cerebellum. By contrast, subtle increases in the superior parietal cortex relate to the additional presence of dystonic symptoms. Although reduced penetrance in DYT11-MD has been attributed to the maternal imprinting epsilon-sarcoglycan mutations, NM-DYT11 carriers showed significant metabolic abnormalities that are not explained by this genetic model.
authors.affiliation: Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Maren
authors.initials: M
authors.lastname: Carbon
authors.forename: Deborah
authors.initials: D
authors.lastname: Raymond
authors.forename: Laurie
authors.initials: L
authors.lastname: Ozelius
authors.forename: Rachel
authors.initials: R
authors.lastname: Saunders-Pullman
authors.forename: Steven
authors.initials: S
authors.lastname: Frucht
authors.forename: Vijay
authors.initials: V
authors.lastname: Dhawan
authors.forename: Susan
authors.initials: S
authors.lastname: Bressman
authors.forename: David
authors.initials: D
authors.lastname: Eidelberg
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D020821:Dystonic Disorders / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics; D005192:Family Health; D005260:Female; D019788:Fluorodeoxyglucose F18; D018392:Genomic Imprinting / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010296:Parietal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D019683:Penetrance; D010641:Phenotype; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D049031:Sarcoglycans / Q000235:genetics*; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism; D055815:Young Adult
chemical_list: C526572:SGCE protein, human; D049031:Sarcoglycans; D019788:Fluorodeoxyglucose F18