Longitudinal Spinal Cord Atrophy in Patients With Neuromyelitis Optica Spectrum Disorder and Its Association With Rituximab Treatment.

Abstract

Longitudinally extensive transverse myelitis (LETM) is a core feature of neuromyelitis optica spectrum disorder (NMOSD), which leads to spinal cord atrophy. We aim to determine annual spinal cord atrophy rates and influencing factors in NMOSD. Spinal cord structural metrics, including cross-sectional area (CSA), anteroposterior diameter (AP), and right-left diameter (RL), were calculated using the Spinal Cord Toolbox from brain 3D sagittal T1-weighted images covering the C1-C3 levels. Normative references were constructed based on healthy participants and used to derive the deviation scores (Z-scores). Annualized atrophy rates were estimated using a linear mixed-effects model. Associations with clinical measures, rituximab treatment, and neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were assessed using partial Pearson correlation, multivariate linear regression, and linear mixed-effects models. In this longitudinal study, 72 patients with NMOSD (233 MRI scans; mean age 40.0 years; 84.7% female) from the CLUE cohort and 2,162 healthy participants were included. In patients with NMOSD, annual atrophy rates were -0.27/y for CSA (95% CI -0.35 to -0.20, <i>p</i> < 0.001), -0.23/y for AP (95% CI -0.33 to -0.13, <i>p</i> < 0.001), and -0.14/y for RL (95% CI -0.20 to -0.09, <i>p</i> < 0.001). A faster AP atrophy rate was associated with longer T2 lesion length and a higher number of relapses (<i>r</i> = -0.35/-0.25, <i>p</i> < 0.05). Prolonged interval from initial LETM to baseline MRI was independently associated with a slower CSA atrophy rate (β = 4.62 × 10^-⁵; 95% CI 0.25 to 9.00 × 10^-5, <i>p</i> = 0.043), while older age (β = -25.17 × 10^-5; 95% CI -39.12 to -11.22 × 10^-5, <i>p</i> < 0.001) and lesion length (β = -55.66 × 10^-5; 95% CI -104.50 to -6.83 × 10^-5, <i>p</i> = 0.029) were related to faster RL atrophy. Rituximab was associated with slower RL atrophy compared with other immunosuppressive therapies (β = 0.02; 95% CI 0.01-0.05; <i>p</i> = 0.044). Elevated serum GFAP levels were correlated with accelerated CSA (<i>r</i> = -0.42/-0.45), AP (<i>r</i> = -0.49/-0.45), and RL (<i>r</i> = -0.37/-0.44) atrophy at baseline/follow-up (all <i>p</i> < 0.01). Increased NfL levels were correlated with faster CSA and RL atrophy at follow-up (<i>p</i> = 0.009, <i>p</i> = 0.031). Spinal cord atrophy in NMOSD progresses annually and is influenced by disease activity and duration. Rituximab was associated with attenuated progression of spinal cord atrophy. Moreover, serum NfL and GFAP may serve as potential biomarkers.