Autoinflammatory characteristics and short-term effects of delivering high-dose steroids to the surface of the intact endolymphatic sac and incus in refractory Ménière's disease

Abstract

Objective To investigate immune-related genetic background in intractable Meniere’s disease (MD) and the immediate results of a novel therapy by delivering steroids to the surface of the intact endolymphatic sac (ES) and incus in a sustainable manner. Case report and methods Candidate genes involved in immune regulation were sequenced using a next-generation sequencing method in a patient with intractable MD. Mutations were confirmed using the Sanger sequencing method. The ES was exposed, and gelatin sponge particles were immersed in high-dose methylprednisolone solution and placed onto the surface of ES. “L”-shaped gelatin sponge strips were immersed in dexamethasone solution and served as a guiding device for the steroids by touching the incus and gelatin sponge particles on the surface of the ES. Gelatin sponge particles immersed in dexamethasone solution were placed around the gelatin sponge strips and sealed using fibrin glue. Results Autoinflammation in the refractory MD case was indicated by genotype, including novel heterozygous mutations of PRF1, UNC13D, SLC29A3, ITCH, and JAK3, as well as phenotype. The vertigo was fully relieved immediately after operation. Tinnitus and aural fullness were resolved 3 weeks after operation, whereas hearing improved in 2 mon postoperation. No recurrence was noted during the 5-monfollow-up, and the final MRI supported the novel therapeutic hypothesis. Conclusion Autoinflammation was involved in a refractory MD. This novel therapy, which involves the delivery of steroids to the surface of the intact ES and incus, is effective in relieving vertigo and tinnitus and improves hearing function of refractory MD.

MEFV, IRF8, ADA, PEPD, and NBAS gene variants and elevated serum cytokines in a patient with unilateral sporadic Meniere's disease and vascular congestion over the endolymphatic sac

“…Immunological detections of hepatitis B and C, syphilis, and human immunodeficiency virus were negative. She received endolymphatic sac delivery of steroids on May 12, 2021, as previously reported ( Zou, 2019 ). Significant vascular congestion was visualized surrounding the ES during surgery ( Fig.…”

“…Genomic DNA was extracted from the peripheral blood sample, and the whole exomes of 423 candidate genes potentially involved in diseases associated with immune reactions were selected according to Human Phenotype Ontology ( http://human-phenotype-ontology.github.io/ ) and sequenced with next-generation sequencing ( Zou et al., 2016 ). The data were analyzed, and the clinical significance of allelic variants was judged as previously reported ( Zou, 2019 ). The following heterozygous variants were detected ( Table 1 ): an autosomal-dominant inherited variant in Mediterranean fever (MEFV) (c.442G > C), an autosomal-dominant/recessive inherited variant in interferon regulatory factor 8 (IRF8) (c.1157G > T), autosomal-recessive inherited but pathologic variants in adenosine deaminase (ADA) (c.445C > T) and peptidase D (PEPD) (c.151G > A), and an autosomal-recessive inherited but limited pathologic variant in neuroblastoma-amplified sequence (NBAS) (c.4049T > C).…”

Hearing restoration and the stria vascularis: evidence for the role of the immune system in hearing restoration

“…Given the evidence for cytokine signalling within the adult mouse stria vascularis and in autoinflammatory and autoimmune disorders, we will now discuss therapeutic targeting of these signalling pathways. Given that treatment with steroids represents the first-line treatment of these disorders [34,42,64,65 ▪ ,66–73,74 ▪ ,75,76 ▪ ,77,78 ▪ ], understanding cytokine signalling in patients with steroid-responsive and steroid-unresponsive disease offers an opportunity to identify critical entry points for therapeutic immunomodulation. Corticosteroids repress IL-6 expression via inhibiting the interaction between NF-IL6 and the p65 subunit of NF- κ B [79].…”

Elevated G-CSF, IL8, and HGF in patients with definite Meniere’s disease may indicate the role of NET formation in triggering autoimmunity and autoinflammation

“…A link between thyroid autoimmunity and MD was also proposed 8,9 . In addition to potential autoimmunity, autoinflammatory mechanisms may also be involved in the development of MD [9][10][11][12][13][14][15] . However, the detailed mechanism of eliciting either autoimmunity or autoinflammation involved in MD has not yet been clarified.…”