Sustained hippocampal neuroinflammation and subsequent glutamatergic dysfunction in juvenile idiopathic arthritis: evidence from proton magnetic resonance spectroscopy (1H-MRS).

BACKGROUND

Chronic pain and psychiatric comorbidities in juvenile idiopathic arthritis (JIA) persist even during disease remission, suggesting central nervous system (CNS) alterations. This study used proton magnetic resonance spectroscopy (1H-MRS) to investigate neurometabolic changes in the right hippocampus of JIA patients across active and inactive disease phases.

METHODS

A cohort of 248 JIA patients (61 treatment-naïve patients with active JIA and 187 patients with inactive JIA) and 57 healthy controls (HCs) underwent 1H-MRS of the right hippocampus. Metabolite ratios of total N-acetylaspartate (tNAA), total choline (tCho), myo-inositol (mI), glutamate (Glu), and glutamate-glutamine complex (Glx) relative to total creatine (tCr) were quantified. Associations with systemic inflammation (ESR and CRP) and clinical indices (JADAS-27 and CHAQ) were evaluated.

RESULTS

Compared with HCs, both JIA groups showed elevated mI/tCr and reduced Glu/tCr and Glx/tCr in the inactive JIA group (all, P < 0.05). mI/tCr was positively correlated with ESR (rho = 0.269) and CRP (rho = 0.287) in active JIA patients. However, the results did not survive the rigid multiple correction. Notably, tNAA/tCr, tCho/tCr, Glu/tCr and Glx/tCr showed no significant correlations with systemic inflammation and clinical indices for treatment-naïve and inactive JIA patients.

CONCLUSIONS

Sustained hippocampal neuroinflammation (indicated by elevated mI/tCr) and the subsequent glutamatergic synaptic dysfunction (indicated by reduced Glu/tCr and Glx/tCr) were identified in JIA patients. Peripheral inflammation may drive microglial activation during active disease, highlighting the hippocampus as a vulnerable CNS target in chronic inflammatory states.