title: Sensitivity of quantitative (1)H magnetic resonance spectroscopy of the brain in detecting early neuronal damage in systemic lupus erythematosus.
abstract: OBJECTIVE
  To quantify N-acetylaspartate (NAA), total creatines (tCr), total cholines (tCho), and myo-inositol (mI) levels in normal and abnormal appearing white matter of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) in order to determine the specific changes in metabolite concentrations.
  
  
  METHODS
  Axial proton density and T(2) weighted magnetic resonance images, and short echo time (TE 30 ms) (1)H spectra were acquired with a GE SIGNA 1.5 T magnetic resonance system. Concentrations of NAA, tCr, tCho, and mI were determined, using brain tissue water as a reference, from nine patients (seven female, mean age 40.3 years, range 16-65) with NPSLE and eight healthy women (mean age 43 years, range 31-65).
  
  
  RESULTS
  A significant rise of tCho (12.4%, p<0.05) and mI (31.4%, p<0.005) and a significant reduction in NAA (-12%, p<0.05) was found in normal appearing white matter compared with controls. Analysis according to severity of the clinical NPSLE features (subgrouped as major or minor) showed that SLE major had reduced NAA compared with SLE minor (-18.4%, p<0.05) and controls (-20%, p<0.005). The SLE major group showed a significant rise of mI (32%, p<0.01) and the SLE minor group a significant increase in tCho (18.6%, p<0.05) compared with controls. Longitudinal analysis of brain metabolites in normal appearing white matter showed consistent abnormalities in NAA, tCho, and mI in a patient with stable clinical features and a constant rise of tCho, but transient rise of mI was seen during a flare of disease in another patient.
  
  
  CONCLUSIONS
  Quantitative (1)H magnetic resonance spectroscopy (MRS) suggests a particular course of neurometabolite changes that precedes irreversible reductions in NAA and permanent neuronal loss. Initially, in patients with SLE minor, there is a significant rise in tCho and a trend (reversible) for mI also to be raised. In patients with SLE major the NAA is significantly and permanently reduced and mI is significantly raised, whereas the tCho levels are near normal. Further investigations are needed to determine how specific MRS is as a clinical marker for brain disturbance in SLE.
authors.affiliation: Academic Unit for Musculoskeletal Disease, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. j.axford@sgms.ac.uk
authors.forename: J S
authors.initials: JS
authors.lastname: Axford
authors.forename: F A
authors.initials: FA
authors.lastname: Howe
authors.forename: C
authors.initials: C
authors.lastname: Heron
authors.forename: J R
authors.initials: JR
authors.lastname: Griffiths
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000032:analysis; D001927:Brain Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology; D016022:Case-Control Studies; D002794:Choline / Q000032:analysis; D003401:Creatine / Q000032:analysis; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007294:Inositol / Q000032:analysis; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D016011:Normal Distribution; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D016756:Immunoglobulins, Intravenous; D001224:Aspartic Acid; D007294:Inositol; D003401:Creatine; D002794:Choline