Gray matter N-acetyl aspartate deficits in secondary progressive but not relapsing-remitting multiple sclerosis.
OBJECTIVE
Spectroscopic examination of multiple sclerosis (MS) patients has revealed abnormally low N-acetyl-aspartate (NAA) signal intensity, even in brain tissue that appears normal on high-resolution structural MR images but has yielded inconclusive evidence to distinguish the well-documented clinical differences between MS subtypes. This study used proton MR spectroscopic imaging (MRSI) and high-resolution MR imaging to characterize metabolite profiles in normal-appearing brain tissue of relapsing-remitting multiple sclerosis (RRMS) and secondary progressive (SP) MS.


METHODS
Volumetric spiral MRSI was used together with high-resolution MR imaging to derive absolute measures of metabolite concentrations separately in normal-appearing supratentorial cerebral gray matter and white matter in five RRMS patients, five SPMS patients, and nine age-matched controls. Structural MR images were segmented into compartments of gray matter, white matter, CSF, and lesions, and metabolite signals per unit of tissue volume were calculated for gray matter and white matter separately.


RESULTS
Only the SPMS group had significantly lower NAA concentrations in normal-appearing gray matter compared with concentrations in controls. NAA in normal-appearing white matter was equally reduced in RRMS and SPMS patients. The functional relevance of this brain metabolite measure was suggested by the observed but statistically nonsignificant correlation between higher disability scores on the Expanded Disability Status Scale and lower gray matter NAA concentrations.


CONCLUSIONS
The otherwise occult abnormality in supratentorial gray matter in SPMS but not RRMS may explain the more severe physical and cognitive impairments afflicting patients with SPMS that do not correlate well with visible lesion burden.
Adalsteinsson
Elfar
E
Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
Langer-Gould
Annette
A
Homer
Ronald J
RJ
Rao
Archana
A
Sullivan
Edith V
EV
Lima
Christiane Abbehusen
CA
Pfefferbaum
Adolf
A
Atlas
Scott W
SW
D000328:Adult; D000704:Analysis of Variance; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000172:deficiency* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000378:metabolism*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000378:metabolism*; D009994:Osmolar Concentration; D010487:Periaqueductal Gray / Q000378:metabolism*
D001224:Aspartic Acid; C000179:N-acetylaspartate