Correlation of GABA⁺ levels in the medial prefrontal cortex and circulating follicular helper T cells in neuromyelitis optica spectrum disorder patients with cognitive impairment

Background: Neuromyelitis optica spectrum disorder (NMOSD) associated with cognitive impairment (CI) is acknowledged. However, the underlying pathogenesis and involvement of the immune system remain unclear. Objectives: This study aimed to investigate the alterations in immune cells, cytokines, and GABA+ levels in NMOSD patients with cognitive deficits. MethodsThirty-eight NMOSD patients and 38 healthy controls (HCs) were included. NMOSD patients were stratified as NMOSD-CI and NMOSD-CP groups. The difference in cognitive functions, Tfh and cytokines, and GABA+ levels were assessed, and their correlations were calculated. Results: NMOSD-CI patients showed worse performance on all cognitive tests, and the percentage of circulating follicular helper T cells (cTfh) was significantly elevated. The frequency of cTfh was positively and negatively correlated with Stroop-A and AVLT long-delayed scores, respectively. IL-21 was remarkably higher in NMOSD-CI and NMOSD-CP. The level of GABA+ in medial prefrontal cortex (mPFC) was significantly decreased in NMOSD-CI and was proved positively and negatively correlated with Symbol Digit Modalities Test and the frequency of circulating Tfh cells, respectively. Conclusion: In NMOSD-CI patients, all cognitive domains were impacted, , while GABA+ levels in mPFC were decreased. GABA+ levels in NMOSD-CI were negatively correlated with the frequency of cTfh, suggesting the underlying coupling mechanism between immune responses and neurotransmitter metabolism in CI in NMOSD patients.