Reduced NAA in motor and non-motor brain regions in amyotrophic lateral sclerosis: a cross-sectional and longitudinal study.
OBJECTIVE
After replication of previous findings we aimed to: 1) determine if previously reported (1)H MRSI differences between ALS patients and control subjects are limited to the motor cortex; and 2) determine the longitudinal metabolic changes corresponding to varying levels of diagnostic certainty.


METHODS
Twenty-one patients with possible/suspected ALS, 24 patients with probable/definite ALS and 17 control subjects underwent multislice (1)H MRSI co-registered with tissue-segmented MRI to obtain concentrations of the brain metabolites N-acetylaspartate (NAA), creatine, and choline in the left and right motor cortex and in gray matter and white matter of non-motor regions in the brain.


RESULTS
In the more affected hemisphere, reductions in the ratios, NAA/Cho and NAA/Cre+Cho were observed both within (12.6% and 9.5% respectively) and outside (9.2% and 7.3% respectively) the motor cortex in probable/definite ALS. However, these reductions were significantly greater within the motor cortex (P<0.05 for NAA/Cho and P<0.005 for NAA/Cre+Cho). Longitudinal changes in NAA were observed at three months within the motor cortex of both possible/suspected ALS patients (P<0.005) and at nine months outside the motor cortex of probable/definite patients (P<0.005). However, there was no clear pattern of progressive change over time.


CONCLUSIONS
NAA ratios are reduced in the motor cortex and outside the motor cortex in ALS, suggesting widespread neuronal injury. Longitudinal changes of NAA are not reliable, suggesting that NAA may not be a useful surrogate marker for treatment trials.
Rule
R R
RR
Department of Radiology, University of California, San Francisco, CA, USA. ruler@itsa.ucsf.edu
Suhy
J
J
Schuff
N
N
Gelinas
D F
DF
Miller
R G
RG
Weiner
M W
MW
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000378:metabolism*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001931:Brain Mapping; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000378:metabolism* / Q000473:pathology; D012016:Reference Values; D014316:Tritium / Q000378:metabolism
D014316:Tritium; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline