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Relapsing-remitting Multiple Sclerosis and Whole-Brain N-Acetylaspartate Measurement: Evidence for Different Clinical Cohorts—Initial Observations¹

¹ From the Department of Radiology, New York University School of Medicine, 560 First Ave, New York, NY 10016 (O.G., D.M.M., B.S.Y.L., J.S.B., J.H., R.I.G.); and Department of Neurology, University of Pennsylvania Medical Center, Philadelphia (J.L., D.J., C.E.M.). Received July 26, 2001; revision requested September 6; final revision received March 13, 2002; accepted March 25. Supported by NIH grants NS33385, NS37739, and NS29029. Address correspondence to R.I.G. (e-mail: robert.grossman@med.nyu.edu).

PURPOSE: To quantify the rate of concentration decline of neuronal marker N-acetylaspartate (NAA) in the entire brain of patients with relapsing-remitting multiple sclerosis (MS) in relation to healthy age-matched control subjects.

MATERIALS AND METHODS: Whole-brain NAA (WBNAA) concentration was quantified in 49 patients with relapsing-remitting MS by using magnetic resonance (MR) imaging and proton MR spectroscopy. It was statistically analyzed by using Spearman rank correlation coefficients to test the intragroup relationship between WBNAA and Expanded Disability Status Scale (EDSS) score and Mann-Whitney analyses to test for differences between subgroups’ EDSS scores versus previously published WBNAA values for healthy subjects, disease duration, and age.

RESULTS: Analyses indicated three subgroups of WBNAA dynamics: Ten patients’ conditions were "stable," exhibiting an insignificant change of about 0% (0.02/14.37) per year of clinically definite disease duration (P = .54); 27 patients showed "moderate" decline, -2.8% (-0.34/12.18) per year (P < .01); and 12 patients experienced "rapid" decline, -27.9% (-3.39/12.14) per year (P < .01). No correlation was found between WBNAA deficit, EDSS score, and age.

CONCLUSION: Ascertaining an individual’s NAA concentration dynamics might enable early forecast of disease course, reflect disease severity and thus influence treatment decisions, and improve clinical trial efficiency by allowing selection of candidates on the basis of WBNAA dynamics in addition to clinical status.

© RSNA, 2002

Index terms: Magnetic resonance (MR), spectroscopy, 10.12145 • Sclerosis, multiple, 10.871

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