Longitudinal Cortical Surface Signatures Distinguish Neuromyelitis Optica Spectrum Disorder from Multiple Sclerosis

Neuromyelitis optica spectrum disorder (NMOSD) is a chronic condition driven by selective injury to aquaporin 4 (AQP4) channels. Accurate diagnosis and effective disease surveillance are critical to preventing permanent neurological disability. Targeted imaging of cortical gyri and sulci was explored due to the widespread AQP4 distribution, enabling comparison with multiple sclerosis (MS).

A retrospective study at a single academic center involving people with NMOSD and MS, each having 2-8 MRI time points. Longitudinal cortical surface-based morphometry and conventional cortical grey matter volumes were quantified in isolated gyri and sulci.

Sixty-two individuals were included (31 fulfilling international panel criteria for NMOSD and 31 meeting 2017 McDonald criteria for MS), yielding 113 NMOSD and 133 MS MRI studies for analysis. NMOSD subjects were older (median age: 48.8 years (y), range (23.2-87.5y)) compared to those with MS (median age: 42.8y, (30.0-57.6y)). When analyzed separately by group, individuals with NMOSD demonstrated a significant annual decline in 3-dimensional (3D) cortical gyri volume (-0.0514 mm3/year, 95% Confidence Interval (CI)=[-0.0859, -0.0168]), whereas no significant change was observed in those with MS (0.0118 mm3/year, 95% CI=[-0.0275, 0.0512]). Additionally, between groups, the annualized rate of 3D cortical gyri volume decline was significantly greater in NMOSD when compared with MS, with a difference of -0.0632 mm3/year observed (95% CI=[-0.1019, -0.0246], p=0.003). No significant change in average sulci volume was observed for those with MS (0.0022 mm3/year, 95% CI=[-0.0070, 0.0114]) or with NMOSD (-0.0062 mm3/year, 95% CI=[-0.0155, 0.0031]), and no difference between groups was identified. Prior relapses were not associated with changes in gyral or sulcal volumes per year in NMOSD or MS.

Longitudinal reductions in distinct cortical regions may serve as an ideal metric for differentiating NMOSD from MS and may provide evidence of subclinical disease activity.