Brain corticospinal tract abnormalities in aquaporin-4 seropositive neuromyelitis optica spectrum disorder with longitudinally extensive transverse myelitis

Widespread white matter changes, including those in the corticospinal tract (CST), have been observed in patients with neuromyelitis optica spectrum disorder (NMOSD). However, whether these alterations originate within the brain or result from spinal cord damage remains unclear. To investigate the CST alteration in AQP4-IgG positive NMOSD with longitudinally extensive transverse myelitis (LETM), and evaluate its relevance to LETM via fixel-based analysis. AQP4+ LETM patients and healthy controls were from ongoing clinical and imaging patterns of neuroinflammation diseases in China cohort between December 2018 and September 2023. Fibre density, fibre cross-section, and the combined measure of fibre density and fibre cross-section were calculated in CST. Serum neurofilament light chain and glial fibrillary acidic protein levels were determined using single-molecule arrays. Multivariate linear model was used to assess associations in AQP4+ LETM between fixel parameters and clinical variables. 44 AQP4+ LETM and 48 healthy controls were included in the study. Among AQP4+ LETM, CST exhibited a decreased mean fibre cross-section (<i>P</i> = 0.001) and the combined measure of fibre density and cross-section (<i>P</i> = 0.004) compared to controls, particularly pronounced in the inferior segments. Negative associations were revealed: pyramidal function score with fibre density (<i>r</i> = -0.335, <i>P</i> = 0.037); LETM segments with fibre density (<i>r</i> = -0.429, <i>P</i> = 0.006); and the combined measure of fibre density and cross-section with duration of pyramidal tract impairment (<i>r</i> = -0.349, <i>P</i> = 0.032) and LETM segment (<i>r</i> = -0.384, <i>P</i> = 0.014). Serum neurofilament light chain and glial fibrillary acidic protein were elevated in AQP4+ LETM than healthy controls (<i>P</i> < 0.0001). Serum neurofilament light chain was negatively related to the combined measure of fibre density and cross-section (<i>r</i> = -0.428, <i>P</i> = 0.01) and fibre cross-section (<i>r</i> = -0.379, <i>P</i> = 0.025). Distinct reduction of fibre cross-section and the combined measure of fibre density and cross-section in brain CST were observed in AQP4+ LETM. The fixel parameters of CST in AQP4+ LETM were negatively correlated with the severity and duration of LETM impairment.