title: Presymptomatic spinal cord neurometabolic findings in SOD1-positive people at risk for familial ALS.
abstract: OBJECTIVE
  It has been speculated that amyotrophic lateral sclerosis (ALS) is characterized by a premanifest period during which neurodegeneration precedes the appearance of clinical manifestations. Magnetic resonance spectroscopy (MRS) was used to measure ratios of neurometabolites in the cervical spine of asymptomatic individuals with a mutation in the SOD1 gene (SOD1+) and compare their neurometabolic ratios to patients with ALS and healthy controls.
  
  
  METHODS
  A cross-sectional study of (1)H-MRS of the cervical spine was performed on 24 presymptomatic SOD1+ volunteers, 29 healthy controls, and 23 patients with ALS. All presymptomatic subjects had no symptoms of disease, normal forced vital capacity, and normal electromyographic examination. Relative concentrations of choline (Cho), creatine (Cr), myo-inositol (Myo), and N-acetylaspartate (NAA) were determined.
  
  
  RESULTS
  NAA/Cr and NAA/Myo ratios are reduced in both SOD1+ subjects (39.7%, p = 0.001 and 18.0%, p = 0.02) and patients with ALS (41.2%, p < 0.001 and 24.0%, p = 0.01) compared to controls. Myo/Cr is reduced (10.3%, p = 0.02) in SOD1+ subjects compared to controls, but no difference was found between patients with ALS and controls. By contrast, NAA/Cho is reduced in patients with ALS (24.0%, p = 0.002), but not in presymptomatic SOD1+ subjects compared to controls.
  
  
  CONCLUSIONS
  Changes in neurometabolite ratios in the cervical spinal cord are evident in presymptomatic SOD1+ individuals in advance of symptoms and clinical or electromyographic signs of disease. These changes reflect a reduction in NAA/Cr and NAA/Myo. Neurometabolic changes in this population resemble changes observed in patients with clinically apparent ALS. This suggests that neurometabolic changes occur early in the course of the disease process.
authors.affiliation: Carolinas HealthCare System, Charlotte, NC, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Carew
authors.forename: G
authors.initials: G
authors.lastname: Nair
authors.forename: P M
authors.initials: PM
authors.lastname: Andersen
authors.forename: J
authors.initials: J
authors.lastname: Wuu
authors.forename: S
authors.initials: S
authors.lastname: Gronka
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.forename: M
authors.initials: M
authors.lastname: Benatar
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D016022:Case-Control Studies; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003430:Cross-Sectional Studies; D005192:Family Health; D005260:Female; D006801:Humans; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D012307:Risk Factors; D013116:Spinal Cord / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D014316:Tritium
chemical_list: C000606290:SOD1 protein, human; D014316:Tritium; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D003401:Creatine; D002794:Choline