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

Abstract

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.

Double-negative neuromyelitis optica spectrum disorder

“…Interestingly, identified subgroups differed significantly with respect to N-acetylaspartate a neuronalaxonal marker in the cervical spinal cord with lower N-acetylaspartate in "MS-like" patients along with a lower occurrence of LETM compared with "classic NMOSD-like" patients. 34 The metabolic differentiators measured in the patient serum: myoinositol and formate, previously shown to differentiate MS from the two antibody conditions together, were also shown to validate principal component analysis spontaneously separating DN NMOSD-like groups into "MS like" and "NMOSD like" groups. 45…”

“… 33 DN patients with overlapping features of NMOSD and MS have been largely understudied as they might not fulfill neither MS nor NMOSD criteria and, therefore, are not included in research cohorts (“forgotten patients”). In recent studies aimed at elucidating the structure of DN NMOSD cohort, 33 , 34 the inclusion criteria were broadened to include all patients who have at least one NMOSD feature.…”