# Anterograde and trans-synaptic neurodegeneration in aquaporin-4-antibody neuromyelitis optica spectrum disorder patients with a history of transverse myelitis

## TL;DR

Patients with a specific autoimmune disease and a history of spinal inflammation show sensory pathway neurodegeneration linked to disability.

## Contribution

Identifies anterograde and trans-synaptic neurodegeneration in sensory pathways of AQP4-NMOSD patients with transverse myelitis using advanced MRI.

## Key findings

- AQP4-NMOSD patients with TM show reduced spinal cord cross-sectional area and fractional anisotropy.
- Sensory pathway changes include higher isotropic volume fraction in VPL nuclei and reduced neurite density in thalamic radiation.
- Neurite density in VPL nuclei correlates with disability status in patients.

## Abstract

Neuromyelitis optica spectrum disorder associated with aquaporin-4-antibodies (AQP4-NMOSD) is an autoimmune disease of the CNS with a high risk of visual, motor and sensory disability secondary to optic neuritis (ON) and transverse myelitis (TM) attacks. The degree of recovery is difficult to predict and may be affected by the extent of ensuing neurodegeneration. While neurodegeneration in AQP4-NMOSD is reported in the visual system after ON, its occurrence in patients with TM remains largely unknown. The aim of this study was to use advanced MRI to cross-sectionally examine the sensory and motor pathways in 18 AQP4-NMOSD patients with a history of TM and 20 healthy controls. The results showed that AQP4-NMOSD patients had decreased cross-sectional area (mean 63.62 versus 70.75, P = 0.016) and reduced fractional anisotropy (mean 0.60 versus 0.65, P = 0.014) in the cervical spinal cord, and changes in the sensory, but not motor, cerebral pathway as evidenced by higher isotropic volume fraction in the ventral posterolateral (VPL) nuclei (mean 0.06 versus 0.05, P = 0.03), reduced neurite density in the right superior thalamic radiation and lower T1 relaxation rates in the primary somatosensory cortex (mean 0.72 versus 0.74, P = 0.04) when compared with healthy controls. Neurite density in the VPL nuclei significantly correlated with the Expanded Disability Status Scale (r = −0.469, P < 0.05). In conclusion, AQP4-NMOSD patients who had TM display features of anterograde and trans-synaptic neurodegeneration in the sensory pathway, which correlate with clinical outcomes. Further studies will clarify the temporal dynamics of such changes and their potential utility as clinical trial outcomes.

Jakuszyk et al. report that patients with neuromyelitis optica spectrum disorder associated with aquaporin-4 antibodies and a history of transverse myelitis show neurodegeneration in sensory pathways, including spinal cord white matter and thalamocortical regions. Advanced MRI findings correlate with disability, suggesting biomarkers for disease progression and treatment evaluation.

Graphical Abstract