Total brain N-acetylaspartate - A new measure of disease load in MS

Objective: To quantitate the extent of neuronal cell loss in MS via the who le 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 an d 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 W BNAA 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 th an their matched controls (p < 0.005). This difference was greater among ol der than younger subjects. The linear prediction equations of WBNAA with ag e indicate a faster, x10, decline in the patients, similar to 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 neurona l cell loss is a cardinal feature of this disease. WBNAA offers a quick, hi ghly reproducible measure of disease progression and may be an important ma rker of treatment efficacy in MS as well as other neurodegenerative disease s.