title: Longitudinal metabolite changes in Huntington's disease during disease onset.
abstract: BACKGROUND
  Previous cross-sectional magnetic resonance spectroscopy (MRS) studies in Huntington's disease (HD) have demonstrated differences in metabolite concentrations in several regions of interest, especially the putamen and caudate nucleus.
  
  
  OBJECTIVE
  To assess metabolite changes in both premanifest and early HD over a two year follow up period using MRS at 7 Tesla in several regions of interest.
  
  
  METHODS
  In 13 HD gene carriers (10 premanifest and 3 manifest HD) proton MRS was performed at baseline and after 24 months. At follow up, four of the premanifest HD gene carriers had progressed into manifest HD, as assessed by clinical measures. 7T MR proton spectroscopy was performed in three regions of interest; the caudate nucleus, putamen and prefrontal cortex. Six metabolites were quantified for each region at each time point. Statistical analysis was performed using Wilcoxon signed rank tests.
  
  
  RESULTS
  Across all subjects, a longitudinal decrease in the caudate nucleus in creatine (p = 0.038) and myo-inositol (p = 0.015) concentrations was found. A significant decrease in the putamen was seen in the total N-acetylaspartate (tNAA) (p = 0.028) and choline concentrations (p = 0.028). For premanifest HD converters, a non-significant high rate of tNAA decrease in the putamen was found compared to non-converting premanifest HD.
  
  
  CONCLUSIONS
  Over a two year period we have demonstrated metabolite changes in the caudate nucleus and putamen of HD gene carriers around disease onset. This demonstrates the potential of MRS for providing a biomarker of disease progression and for evaluating future therapeutic interventions.
authors.affiliation: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Simon J A
authors.initials: SJ
authors.lastname: van den Bogaard
authors.affiliation: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Eve M
authors.initials: EM
authors.lastname: Dumas
authors.affiliation: C.J. Gorter Centre for High Field MRI, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Wouter M
authors.initials: WM
authors.lastname: Teeuwisse
authors.affiliation: C.J. Gorter Centre for High Field MRI, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Hermien E
authors.initials: HE
authors.lastname: Kan
authors.affiliation: C.J. Gorter Centre for High Field MRI, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Andrew
authors.initials: A
authors.lastname: Webb
authors.affiliation: Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.affiliation: Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Raymund A C
authors.initials: RA
authors.lastname: Roos
authors.affiliation: Department of Radiology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Grond
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002421:Caudate Nucleus / Q000737:chemistry / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods*; D017397:Prefrontal Cortex / Q000737:chemistry / Q000378:metabolism; D011699:Putamen / Q000737:chemistry / Q000378:metabolism
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate; D003404:Creatinine
keywords: Huntington's disease; MRS; NAA; biomarker; neurodegenerative disorders