Decreased N-acetylaspartate in motor cortex and corticospinal tract in ALS.
The primary objectives of this study were to test whether 1) N-acetylaspartate (NAA), a neuronal marker, is reduced in motor cortex and corticospinal-tract (CST) brain regions of ALS patients; and 2) motor cortex NAA correlates to a clinical measurement of upper motor neuron function in ALS patients. Ten probable or definite ALS patients and nine neurologically normal control subjects were studied. Three axial planes of two-dimensional 1H MRSI data were collected, using a single spin-echo multislice sequence (TE140/TR2000). Two of the 1H MRSI planes were positioned superior to the lateral ventricles, and one plane was positioned at the level of the internal capsule. Spectroscopy voxels were selected from motor cortex, frontal cortex, parietal cortex, medial gray matter, centrum semiovale white matter, anterior internal capsule, and posterior internal capsule. Peak integrals were obtained for the three major 1H MRSI singlet resonances, NAA, creatine and phosphocreatine (Cr), and cholines (Cho). Maximum finger-tap rate was used as a clinical measurement of upper motor neuron function. In ALS, brain NAA/(Cho+Cr) was reduced 19% (p=0.024) in the motor cortex and 16% (p=0.021) in the CST (centrum semiovale and posterior internal capsule) regions. NAA/ (Cho+Cr) was not reduced in frontal cortex, parietal cortex, medial gray matter, or anterior internal capsule. There was a significant relation between ALS motor cortex NAA/(Cho+Cr) and maximum finger-tap rate (r=0.80; p=0.014). NAA/(Cho+Cr) was reduced in motor cortex and CST regions and unchanged in other brain regions of ALS patients when compared with controls. These findings are consistent with the known distribution of neuronal loss in ALS. The positive correlation between motor cortex NAA/(Cho+Cr) and maximum finger-tap rate suggests that reduced NAA/(Cho+Cr) is a surrogate marker of motor cortex neuron loss in ALS. These findings support the study of 1H MRSI NAA measurement as an objective and quantitative measurement of upper motor neuron dysfunction in ALS.
Rooney
W D
WD
Department of Veterans Affairs Medical Center, Department of Radiology, University of California, San Francisco, USA.
Miller
R G
RG
Gelinas
D
D
Schuff
N
N
Maudsley
A A
AA
Weiner
M W
MW
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000378:metabolism*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000378:metabolism*; D011712:Pyramidal Tracts / Q000378:metabolism*; D012016:Reference Values; D014018:Tissue Distribution
D001224:Aspartic Acid; C000179:N-acetylaspartate