title: Two-year serial whole-brain N-acetyl-L-aspartate in patients with relapsing-remitting multiple sclerosis.
abstract: OBJECTIVE
  To test the hypotheses that 1) patients with relapsing-remitting multiple sclerosis (RR-MS) exhibit a quantifiable decline in their whole-brain concentration of the neural marker N-acetyl-L-aspartate (WBNAA), that is 2) more sensitive than clinical changes and 3) may provide a practical outcome measure for proof-of-concept and larger phase III clinical trials.
  
  
  METHODS
  Nineteen patients (5 men and 14 women) with clinically definite RR-MS, who were 33 ± 5 years old (mean ± SD), had a disease duration of 47 ± 28 months, and had a median Expanded Disability Status Scale (EDSS) score of 1.0 (range 0-5.5), underwent MRI and proton magnetic resonance spectroscopy ((1)H-MRS) semiannually for 2 years (5 time points). Eight matched control subjects underwent the protocol annually (3 time points). Their global N-acetyl-L-aspartate (1)H-MRS signal was converted into absolute amounts by phantom replacement and into WBNAA by dividing with the brain parenchymal volume, V(B), from MRI segmentation.
  
  
  RESULTS
  The baseline WBNAA of the patients (10.5 ± 1.7 mM) was significantly lower than that of the controls (12.3 ± 1.3 mM; p < 0.002) and declined significantly (5%/year, p < 0.002) vs that for the controls who did not show a decline (0.4%/year, p > 0.7). Likewise, V(B) values of the patients also declined significantly (0.5%/year, p < 0.0001), whereas those of the controls did not (0.2%/year, p = 0.08). The mean EDSS score of the patients increased insignificantly from 1.0 to 1.5 (range 0-6.0) and did not correlate with V(B) or WBNAA.
  
  
  CONCLUSIONS
  WBNAA of patients with RR-MS declined significantly at both the group and individual levels over a 2-year time period common in clinical trials. Because of the small sample sizes required to establish power, WBNAA can be incorporated into future studies.
authors.affiliation: Department of Radiology, New York University School of Medicine, New York, NY, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Rigotti
authors.forename: M
authors.initials: M
authors.lastname: Inglese
authors.forename: I I
authors.initials: II
authors.lastname: Kirov
authors.forename: E
authors.initials: E
authors.lastname: Gorynski
authors.forename: N N
authors.initials: NN
authors.lastname: Perry
authors.forename: J S
authors.initials: JS
authors.lastname: Babb
authors.forename: J
authors.initials: J
authors.lastname: Herbert
authors.forename: R I
authors.initials: RI
authors.lastname: Grossman
authors.forename: O
authors.initials: O
authors.lastname: Gonen
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis*; D009474:Neurons / Q000473:pathology; D009929:Organ Size / Q000502:physiology; D011237:Predictive Value of Tests; D011379:Prognosis; D013223:Statistics as Topic
chemical_list: D015415:Biomarkers; D001224:Aspartic Acid; C000179:N-acetylaspartate