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From the Division of Medical Science (Dr. Gonen) and Department of Biostatistics (Dr. Babb), Fox Chase Cancer Center, and Departments of Radiology (Drs. Catalaa, Ge, and Grossman, and L.J. Mannon) and Neurology (Dr. Kolson), University of Pennsylvania Medical Center, Philadelphia, PA.
Address correspondence and reprint requests to Dr. Robert I. Grossman, Department of Radiology, University of Pennsylvania Medical Center, Philadelphia, PA 19104; e-mail: grossman{at}oasis.rad.upenn.edu
OBJECTIVE: To quantitate the extent of neuronal cell loss in MS via the whole brain’s N-acetylaspartate (NAA) concentration (WBNAA).
METHODS: Because NAA is assumed to be present only in neuronal cell bodies and their axons, we measured WBNAA as a marker for viable neurons in 12 patients (9 women and 3 men, 26 to 53 years of age) suffering from relapsing-remitting (RR) MS for at least 5 years and compared them with 13 age- and sex-matched normal controls. Total brain NAA was determined with proton MR spectroscopy, and WBNAA was obtained by dividing it by the total brain volume, calculated from high resolution MRI.
RESULTS: The WBNAA of the RR MS patients was lower than their
matched controls (p < 0.005). This difference was greater among
older than younger subjects. The linear prediction equations of WBNAA with
age indicate a faster, x10, decline in the patients, 
0.8% per
year of age (p = 0.022).
CONCLUSION: The age-dependent decrease of whole brain N-acetylaspartate (WBNAA) in the patients suggests that progressive neuronal cell loss is a cardinal feature of this disease. WBNAA offers a quick, highly reproducible measure of disease progression and may be an important marker of treatment efficacy in MS as well as other neurodegenerative diseases.
Key words: N-acetylaspartate—Proton nuclear magnetic resonance spectroscopy—MS
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