9-HODE associates with thalamic atrophy and predicts white matter damage in multiple sclerosis

Background: Multiple sclerosis (MS) is characterized by extensive tissue damage leading to a range of complex symptoms, including physical disability and cognitive dysfunction. Recent work has indicated the clinical relevance of bioactive lipid mediators (LMs), which are known to orchestrate inflammation and its resolution and are deregulated in MS. However, it is unknown whether LM profiles relate to white matter (WM) damage. Objectives: To investigate the potential association between plasma-derived LMs and MRI-quantified WM damage using fractional anisotropy (FA) and grey matter (GM) atrophy in dimethyl fumarate-treated relapsing remitting MS (RRMS) patients. Methods: Severity of FA-based WM damage and GM atrophy was determined in RRMS patients (n = 28) compared to age- and sex-matched controls (n = 31) at treatment initiation (baseline) and after 6 months. Plasma LMs were assessed using HPLC-MS/MS and baseline LMs were correlated to changes in FA and brain volumes. Results: We observed significant WM damage in RRMS patients (mean age 41.4 [SD 9.1]) at baseline and followup (z-score=-0.33 and 0.31, respectively) compared to controls (mean age 41.9 [SD 9.5]; p < 0.001 for both comparisons). Patients with severe WM damage showed a decline of thalamic volume (p = 0.02), and this decline correlated (r = 0.51, p < 0.001) with lower baseline levels of 9-HODE. This LM also predicted FA worsening (beta = 0.14, p < 0.001) over time at 6 months. Conclusion: Despite the relatively small sample size, lower baseline levels of the LM 9-HODE correlated with more thalamic atrophy and predicted subsequent worsening of WM damage in RRMS patients.