Acta neurologica Belgica · 2026
Regional normal-appearing white matter metabolic profiles and cognition in early relapsing-remitting multiple sclerosis: a multi-voxel proton magnetic resonance spectroscopy study.
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Sakalaš Lorand, Suknjaja Vesna, Boban Jasmina
Аннотация
BACKGROUND: Cognitive impairment in multiple sclerosis (MS) is common but only weakly explained by conventional magnetic resonance imaging. Proton magnetic resonance spectroscopy (¹H-MRS) detects microstructural damage in normal-appearing white matter (NAWM). We examined whether regional NAWM metabolic profiles are spatially patterned in early relapsing-remitting MS (RRMS) and whether they relate to cognition.
METHODS: In this cross-sectional study, 52 patients with early RRMS (Expanded Disability Status Scale 0-3; 51 with usable spectroscopy) and 44 matched controls underwent multi-voxel three-dimensional ¹H-MRS at 3 tesla across six supracallosal NAWM regions. Group differences used Mann-Whitney tests with false discovery rate correction, and a group × region analysis tested for disease-related disruption. NAA/Cr-cognition associations used Spearman and partial correlations and multivariable models.
RESULTS: NAA/Cr differed between groups in four of six regions, and a group × region interaction (p < 0.001) indicated that the regional NAA/Cr pattern in RRMS was disrupted beyond the physiological anterior-posterior gradient seen in controls. Frontal NAA/Cr correlated with processing speed (ρ = 0.350, p = 0.012) and parietal NAA/Cr with verbal learning (ρ = 0.327, p = 0.019), but neither survived adjustment for age or parsimonious modelling, in which disability was the main independent correlate of processing speed.
CONCLUSION: Early RRMS shows spatially organised NAWM metabolic disruption. Regional NAA/Cr-cognition associations are detectable but weak and not independent of age or disability, and frontal NAWM integrity relates more to physical function than cognition, supporting a network-disconnection model with limited cognitive specificity. These findings are preliminary and need longitudinal confirmation.
METHODS: In this cross-sectional study, 52 patients with early RRMS (Expanded Disability Status Scale 0-3; 51 with usable spectroscopy) and 44 matched controls underwent multi-voxel three-dimensional ¹H-MRS at 3 tesla across six supracallosal NAWM regions. Group differences used Mann-Whitney tests with false discovery rate correction, and a group × region analysis tested for disease-related disruption. NAA/Cr-cognition associations used Spearman and partial correlations and multivariable models.
RESULTS: NAA/Cr differed between groups in four of six regions, and a group × region interaction (p < 0.001) indicated that the regional NAA/Cr pattern in RRMS was disrupted beyond the physiological anterior-posterior gradient seen in controls. Frontal NAA/Cr correlated with processing speed (ρ = 0.350, p = 0.012) and parietal NAA/Cr with verbal learning (ρ = 0.327, p = 0.019), but neither survived adjustment for age or parsimonious modelling, in which disability was the main independent correlate of processing speed.
CONCLUSION: Early RRMS shows spatially organised NAWM metabolic disruption. Regional NAA/Cr-cognition associations are detectable but weak and not independent of age or disability, and frontal NAWM integrity relates more to physical function than cognition, supporting a network-disconnection model with limited cognitive specificity. These findings are preliminary and need longitudinal confirmation.