TY - JOUR
T1 - Indirect evidence for early widespread gray matter involvement in relapsing-remitting multiple sclerosis
AU - Inglese, Matilde
AU - Ge, Yulin
AU - Filippi, Massimo
AU - Falini, Andrea
AU - Grossman, Robert I.
AU - Gonen, Oded
N1 - Funding Information:
This work was supported by NIH grants EB01015, NS37739, and NS29029 and a grant from the Fondazione Italiana Sclerosi Multipla (M.I.).
PY - 2004/4
Y1 - 2004/4
N2 - Multiple sclerosis (MS) has traditionally been viewed as an inflammatory demyelinating white matter (WM) disease of the central nervous system. However, recent pathology and MRI studies have shown lesions in the gray matter (GM) as well. To ascertain the extent of GM involvement, we obtained with nonlocalizing proton MR spectroscopy the concentration of N-acetylaspartate (NAA), a metabolite found almost exclusively in neuronal cells, T2-lesion loads, and GM and WM fractions in the entire brain of 71 relapsing-remitting (RR) MS patients (51 women, 20 men, 25-55 years old) and 41 healthy controls (27 women, 14 men, 23-55 years old). The average whole-brain NAA (WBNAA) difference between the patients and the controls was -2.9 mM (-22%, P < 0.0001); range: +1.2 to -7. 8 mM (+8% to -63%). The patients' median T2 lesion volume was 5.5 (range: 0.140-28) cm3. GM and WM comprised 50.4 ± 3.8% and 30.4 ± 5.0% (mean ± standard deviation), respectively, of the total brain volume in the patients; 53.8 ± 3.7% and 35.4 ± 4.7% in the controls. Because WM and GM constitute approximately 40% and 60% of the brain parenchyma, respectively, and the NAA concentration in the former is 2/3 of the latter, WBNAA loss greater than 40% × 2/3 = 27% cannot be explained in terms of WM (axonal) pathology alone and must include widespread GM (neuronal) deficits. Therefore, the concept of MS, even at its earlier stages, as a WM disease might need to be reexamined.
AB - Multiple sclerosis (MS) has traditionally been viewed as an inflammatory demyelinating white matter (WM) disease of the central nervous system. However, recent pathology and MRI studies have shown lesions in the gray matter (GM) as well. To ascertain the extent of GM involvement, we obtained with nonlocalizing proton MR spectroscopy the concentration of N-acetylaspartate (NAA), a metabolite found almost exclusively in neuronal cells, T2-lesion loads, and GM and WM fractions in the entire brain of 71 relapsing-remitting (RR) MS patients (51 women, 20 men, 25-55 years old) and 41 healthy controls (27 women, 14 men, 23-55 years old). The average whole-brain NAA (WBNAA) difference between the patients and the controls was -2.9 mM (-22%, P < 0.0001); range: +1.2 to -7. 8 mM (+8% to -63%). The patients' median T2 lesion volume was 5.5 (range: 0.140-28) cm3. GM and WM comprised 50.4 ± 3.8% and 30.4 ± 5.0% (mean ± standard deviation), respectively, of the total brain volume in the patients; 53.8 ± 3.7% and 35.4 ± 4.7% in the controls. Because WM and GM constitute approximately 40% and 60% of the brain parenchyma, respectively, and the NAA concentration in the former is 2/3 of the latter, WBNAA loss greater than 40% × 2/3 = 27% cannot be explained in terms of WM (axonal) pathology alone and must include widespread GM (neuronal) deficits. Therefore, the concept of MS, even at its earlier stages, as a WM disease might need to be reexamined.
KW - Gray matter
KW - Multiple sclerosis
KW - N-acetylaspartate
UR - http://www.scopus.com/inward/record.url?scp=1842608971&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2003.12.008
DO - 10.1016/j.neuroimage.2003.12.008
M3 - Article
C2 - 15050603
AN - SCOPUS:1842608971
SN - 1053-8119
VL - 21
SP - 1825
EP - 1829
JO - NeuroImage
JF - NeuroImage
IS - 4
ER -