Relapsing antibody-negative patients with features of neuromyelitis optica spectrum disorders: Differences inN-acetylaspartate level in the cervical spinal cord indicate distinct underlying processes

Background: Due to lack of biomarkers, antibody-negative patients with features of neuromyelitis optica spectrum disorders (NMOSD) are among the most challenging to diagnose and treat. Using unsupervised clustering, we recently identified ‘MS-like’, ‘spinal MS-like’, ‘classic NMOSD-like’ and ‘NMOSD-like with brain involvement’ subgroups in this cohort. Objective: We used magnetic resonance spectroscopy (MRS) to examine differences in the level of key metabolites in the spinal cord between the four identified subgroups. Methods: Twenty-five relapsing antibody-negative patients with NMOSD features classified by the unsupervised algorithm to one of the subgroups underwent a prospective cervical spinal cord MRS. Spectra from 16 patients fulfilled quality criteria and were included in the analysis. Results: Total N-acetylaspartate (tNAA), but not total choline (tCho) or myo-inositol (Ins), was significantly different between the four subgroups ( p = 0.03). In particular, tNAA was 47.8% lower in the ‘MS-like’ subgroup as compared with the ‘classic NMOSD-like’ subgroup ( p = 0.02). While we found a negative overall correlation between tNAA and disability score ( r = –0.514, p = 0.04) in the whole cohort, the disability score did not differ significantly between the subgroups to explain subgroup differences in tNAA level. Conclusions: Significant differences in the cervical spinal cord tNAA measurements confirm that the previously identified clinico-radiologic subgroups contain patients with distinct underlying disease processes.