Contribution of Myelin Damage to White Matter Changes in Osmotic Demyelination Syndrome

Background/Objectives: Osmotic demyelination syndrome (ODS) causes marked myelin loss with relative axonal preservation. We used diffusion tensor imaging (DTI) to longitudinally assess white matter (WM) changes, hypothesizing that radial diffusivity (RD) would show dynamic recovery alongside clinical improvement. Methods: A 40-year-old woman with ODS and five age-matched female controls underwent DTI at 7 weeks and 6 months post-onset. Metrics were extracted from 27 WM tract categories using atlas-based regions of interest. Lesions were defined by directional dual thresholds (RD_d ≥ 2.0, axial diffusivity [AD] ≤ -2.0, or fractional anisotropy [FA] ≤ -2.0) and confirmed using the Crawford-Howell test with Benjamini-Hochberg FDR correction (q ≤ 0.05). Longitudinal percent change (Δ%) was compared using the Friedman test with Bonferroni-corrected Wilcoxon post hoc tests (α = 0.017). Results: Serum sodium increased from 126 to 138 mmol/L within 24 h, followed by a severe neurological deficit; near-complete recovery by 6 months. At 7 weeks, RD-defined lesions were detected in 10/27 tracts (37.0%)-1/6 brainstem-related and 9/21 non-brainstem-indicating widespread myelin-predominant injury. No AD- or FA-based lesions met criteria, although AD increase in the cingulate gyrus was significant. From 7 weeks to 6 months, the mean Δ% was -0.40 ± 9.38% (AD), -4.73 ± 9.73% (RD), and +7.94 ± 7.53% (FA). Changes differed across metrics (χ²(2) = 24.07, p = 5.92 × 10^-6), with greater RD and FA changes than AD. Conclusions: Early RD-predominant abnormalities preceded RD reduction and FA increase during recovery, consistent with restoration of myelin-related microstructure. Larger studies are warranted.