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

Neurology. 2000 Jan 11;54(1):15-9. doi: 10.1212/wnl.54.1.15.

Abstract

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, approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / metabolism
  • Biomarkers
  • Brain / metabolism*
  • Cell Survival
  • Disease Progression
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / physiopathology
  • Neurons / metabolism
  • Neurons / physiology
  • Reference Values
  • Reproducibility of Results
  • Severity of Illness Index

Substances

  • Biomarkers
  • Aspartic Acid
  • N-acetylaspartate