Reproducibility of three whole-brain N-acetylaspartate decline cohorts in relapsing-remitting multiple sclerosis.
OBJECTIVE
The cross-sectional rate of whole-brain N-acetylaspartate (NAA, a neuronal cell marker) loss in clinically similar relapsing-remitting multiple sclerosis (RRMS) patients has recently been shown to fall into 3 distinct decline rate strata. Our goal was to test the reproducibility of this observation in a new cohort of RRMS patients.


METHODS
Sixteen serial patients (12 women, 4 men, median age 38 [27-55] years) with clinically definite RRMS for an average of 5 (0.3-18) years' disease duration and a mean Expanded Disability Status Score of 2.0 (0-6) were studied, once each. Their whole-brain NAA (WBNAA) amounts, obtained with proton MR spectroscopy, were divided by brain volumes (segmented from MR imaging) to yield concentrations suitable for cross-sectional comparisons.


RESULTS
Three distinct strata of cross-sectional NAA decline rates were found: -0.031, -0.32, and -1.71 mmol/L/y when disease duration was estimated from confirmed diagnosis, or -0.057, -0.20, and -1.38 mmol/L/y when measured from the first clinical symptom. These rates and their corresponding fractions of the study population were indistinguishable from those reported previously in a different group of 49 clinically similar (mean Expanded Disability Status Score also 2.0) RRMS patients.


CONCLUSIONS
Reproducing the previous cohort's cross-sectional WBNAA decline characteristics in this new group of clinically similar RRMS patients indicates that 3 WBNAA loss strata may be a general attribute of MS. Consequently, WBNAA could serve as a surrogate marker for the global load of neuronal and axonal dysfunction and damage in this disease.
Gonen
O
O
Department of Radiology, New York University School of Medicine, New York, NY, USA. oded.gonen@med.nyu.edu
Oberndorfer
T A
TA
Inglese
M
M
Babb
J S
JS
Herbert
J
J
Grossman
R I
RI
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001284:Atrophy; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000378:metabolism* / Q000473:pathology*; D015203:Reproducibility of Results
D001224:Aspartic Acid; C000179:N-acetylaspartate