NAA is a Marker of Disability in Secondary-Progressive MS: A Proton MR Spectroscopic Imaging Study

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FIG 1.
Proton MR spectroscopy slice placement and mask. The upper panel demonstrates slice placement in the sagittal, coronal, and axial planes. The lower panel shows an example of the chemical shift mask for normal-appearing white matter and gray matter.
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FIG 2.
Sample spectra and the chemical shift grid show the position where representative spectra originate, including a lesion (A), accepted spectra in red and lesion in black (B), and spectra from a rejected voxel (C). The position is shown in green in A.
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FIG 3.
Associations between neurometabolites and clinical disability measures. The scatterplots with the line of best fit and 95% confidence intervals are shown for the associations in normal-appearing white matter among the following: A, tNAA/tCr and 9HPT (ρ = 0.23; 95% CI, 0.06–0.40). B, tNAA and Paced Auditory Serial Addition Test (ρ = 0.21; 95% CI, 0.03–0.38). C, tNAA/tCr and Paced Auditory Serial Addition Test (ρ = 0.19; 95% CI, 0.01–0.36). D, mIns/tCr and Paced Auditory Serial Addition Test (ρ = –0.23; 95% CI,–0.39 to −0.05) and in gray matter between tCho and Paced Auditory Serial Addition Test (ρ = –0.24; 95% CI, –0.40 to −0.06) (E).

Table 1:

Baseline demographics and characteristics (n = 119)

↵a Median (range).
↵b The Nine-Hole Peg Test was calculated by taking the reciprocal of the average of 2 trials for each arm and taking the mean.

Table 2:

Results from multiple regression analysis examining associations between neurometabolites and clinical disability measures^{^a}

Predictors	Standardized β	Standardized 95% CI	P
Nine-Hole Peg Test (n = 118)^{^b}
NAWM tNAA/tCr	0.19	0.01–0.36	.04
Paced Auditory Serial Addition Test (n = 119)
NAWM tNAA	0.17	0.01–0.34	.04
Sex^{^c}	–0.23	–0.42 to –0.05	.01
T2 lesion volume	–0.47	–0.64 to –0.30	<.001
Paced Auditory Serial Addition Test (n = 118)^{^d}
NAWM tNAA/tCr	0.19	0.03–0.35	.02
Sex^{^c}	–0.26	–0.44 to –0.08	.006
T2 lesion volume	–0.46	–0.63 to –0.29	<.001
Paced Auditory Serial Addition Test (n = 119)
NAWM mIns/tCr	–0.22	–0.39 to –0.06	.007
Sex^{^c}	–0.25	–0.43 to –0.07	.008
T2 lesion volume	–0.47	–0.64 to –0.30	<.001
Paced Auditory Serial Addition Test (n = 119)
GM tCho	–0.17	–0.33 to –0.01	.04
T2 lesion volume	–0.48	–0.65 to –0.31	<.001

↵a Covariates in the model include age, sex, duration from onset, occurrence of relapse in the 2 years preceding randomization, T2 lesion volume, and normalized brain volume. The table highlights only the predictor variables that were significant from the multiple regression models.
↵b The Nine–Hole Peg Test was calculated by taking the reciprocal of the average of 2 trials for each arm and taking the mean.
↵c Male is reference category.
↵d One hundred eighteen participants in this cohort because 1 case was removed due to a highly leveraged point.