ObjectiveWe investigated correlations among clinical features, degree of inner ear endolymphatic hydrops (EH), and hippocampal volume (HV) in different stages of Meniere's disease (MD).MethodsFrom February 2021 to April 2022, clinical data were collected from 99 patients (39 males, 60 females, mean age: 50.4 ± 10.0 [range: 26–69] years) with unilateral MD admitted to the Department of Vertigo Disease of Shandong ENT Hospital. The left and right ears were affected in 64 and 35 patients, respectively. There were 50 and 49 cases in early (Stages 1, 2) and late stages (Stages 3, 4), respectively. Fifty healthy participants were included as controls. Audiovestibular function test results, EH grading using gadolinium‐enhanced magnetic resonance imaging (MRI), and HV determined on MRI were analyzed for patients at different stages of MD.ResultsBetween‐group comparisons of early and late MD revealed significant differences in the disease course, vestibular function (VF), degree of EH, and HV. There were no significant between‐group differences based on age, sex, affected side, subjective degree of dizziness, hospital anxiety, or depression. Mean HV in patients with early‐stage MD was correlated with the canal paresis value of the caloric test and pure tone hearing threshold, HV in late‐stage patients was correlated with vestibular EH.ConclusionPatients with late‐stage MD exhibited severe auditory and VF impairments, increased EH, and atrophy of the HV. More advanced disease was associated with greater vestibular damage and degree of EH.Level of Evidence3 Laryngoscope, 2023

Ménière’s disease, a multifactorial disorder of the inner ear, is characterized by severe vertigo episodes and hearing loss. Although the role of immune responses in Ménière’s disease has been proposed, the precise mechanisms remain undefined. Here, we show that downregulation of serum/glucocorticoid-inducible kinase 1 is associated with activation of NLRP3 inflammasome in vestibular-resident macrophage-like cells from Ménière’s disease patients. Serum/glucocorticoid-inducible kinase 1 depletion markedly enhances IL-1β production which leads to the damage of inner ear hair cells and vestibular nerve. Mechanistically, serum/glucocorticoid-inducible kinase 1 binds to the PYD domain of NLRP3 and phosphorylates it at Serine 5, thereby interfering inflammasome assembly. Sgk−/− mice show aggravated audiovestibular symptoms and enhanced inflammasome activation in lipopolysaccharide-induced endolymphatic hydrops model, which is ameliorated by blocking NLRP3. Pharmacological inhibition of serum/glucocorticoid-inducible kinase 1 increases the disease severity in vivo. Our studies demonstrate that serum/glucocorticoid-inducible kinase 1 functions as a physiologic inhibitor of NLRP3 inflammasome activation and maintains inner ear immune homeostasis, reciprocally participating in models of Ménière’s disease pathogenesis.

No abstract