Patients showed lower NAA concentration and cross-sectional cord area than controls; there was no difference in axial diffusivity of the spinal cord columns and of the whole spine between patients and controls ().
In patients, the metabolic component of NAA (ResNAA) was associated with disability. In particular, patients with higher ResNAA (greater mitochondrial function) were less likely to have higher EDSS (greater disability) (odds ratio=0.09, p=0.034, 95%Confidence Intervals (CIs) 0.01,0.84) (). Lower ResNAA was associated with worse walking ability, as measured by TWT and MSWS12 (inverse TWT: p=0.024, parameter estimate (PE)=0.026, 95%CIs 0.004,0.05; MSWS-12: p=0.013, PE=−10.7, 95%CIs −18.4,−2.9) ().
Figure 2 Relationship between the residual variance in NAA concentration after taking into account structural imaging measures and clinical scores. (a): Scatter plot of ResNAA vs. EDSS (Rsq=0.5) with a fitted line. (b): Scatter plot of ResNAA vs. TWT (Rsq=0.42). (more ...)
For the multiple regression models, greater NAA itself was associated with lower EDSS (lower disability) (PE: −2.063, p=0.012, 95%CIs −3.49,−0.64), and better walking ability (inverse TWT: PE: 50.1, p=0.031, 95%CIs 6.5,93.7; MSWS12: PE: −0.14, p=0.012, 95%CIs −0.24,−0.04). NAA was not associated with axial diffusivity of the spinal cord columns (for EDSS, PE=0.002, p=0.5; for TWT, PE=0.004, p=0.2; for MSWS12, PE=0.005, p=0.1) or cord cross-sectional area (for EDSS, PE=0.03, p=0.7; TWT, PE=0.09, p=0.3; and MSWS12, PE=0.09, p=0.2). This suggests that the relationship between NAA and clinical disability is preserved after simultaneously adjusting for the structural components of NAA and so is very likely to be determined by its metabolic component.
When the analysis was repeated using the mean axial diffusivity of the whole spinal cord (C1 to C3), instead of the spinal cord columns, similar significant results were obtained; in particular, lower ResNAA was associated with greater disability, as measured by EDSS (odd ratio=0.13, p=0.039, 95%CIs 0.02,0.9), TWT (p=0.013, PE.=0.025, 95%CIs 0.007,0.04) and MSWS12 (p=0.008, PE=−10.1, 95%CIs −16.8,−3.4). In addition, greater NAA itself was associated with lower disability, as measured by EDSS (PE=−1.95, p=0.009, 95%CIs −3.24,−0.66), TWT (PE=51.1, p=0.015, 95%CIs 13.5,88.7), and MSWS12 (PE=−0.14, p=0.007, 95%CIs −0.23,−0.05), when adjusting for axial diffusivity of the entire spinal cord and cord cross-sectional area, which were not significantly associated with NAA (PEs and p values for axial diffusivity in the entire spinal cord in the models with EDSS, TWT and MSWS12 were: 0.001, p=0.6; 0.006, p=0.1, and 0.006, p=0.07, respectively; PEs and p values for cord cross-sectional area in the models with EDSS, TWT and MSWS12 were: 0.02, p=0.8; 0.11, p=0.1, and 0.1, p=0.2, respectively).