No abstract

Objectives Gradually progressive sensorineural hearing loss (SNHL) is a prevalent sensory defect. It is generally untreatable, making rehabilitation by hearing aid or cochlear implantation the only option. However, SNHL as one of the symptoms of the hereditary autoinflammatory systemic disease cryopyrin-associated periodic syndrome, or as the only symptom of the cochlea-specific form (DFNA34), was suggested to respond to IL-1 antagonist (anakinra) therapy, which ameliorates NLRP3 variants-induced over-secretion of IL-1β. We analysed genotypic and phenotypic spectrum of cryopyrin-associated periodic syndrome or DFNA34, specifically focusing on the responsiveness of SNHL to anakinra. Methods Seventeen families diagnosed with either cryopyrin-associated periodic syndrome or DFNA34 were recruited. Genotyping and phenotyping including audiogram, MRI findings, and in vitro IL-1β assay were performed. Results Our cohort had an etiologic homogeneity of 94.1% to NLRP3 variants and a high de novo occurrence (84.6%). We identified the second DNFA34 pedigree worldwide with a novel NLRP3 variant supported by in vitro analysis. Significant improvement of hearing status against the natural course, showing response to anakinra, was identified in three probands, one of whom used to have severe SNHL. Hearing threshold worse than 60 dB at the start of anakinra and cochlear enhancement on brain MRI seemed to be related with poor audiologic prognosis and responsiveness to anakinra therapy despite stabilized systemic symptoms and inflammatory markers. Conclusion We propose a constellation of biomarkers comprising NLRP3 genotypes, hearing status at diagnosis, and cochlear radiological findings as prognostic factors of hearing status after anakinra treatment and possibly as sensitive parameters for treatment dosage adjustment.

Objectives: Recent studies have shown that cochlear duct length (CDL) varies among individuals and could significantly influence the final position of the electrode and its trajectory in the cochlea. Given this, we hypothesized that the degree of modiolar proximity of novel slim modiolar electrodes, such as CI532 and CI632, can also be affected by CDL. To test this hypothesis, we retrospectively evaluated individual CDL to determine if there is any significant correlation of CDL with degree of modiolar proximity. Methods: Fifty-one ears from 38 subjects implanted with slim modiolar electrodes by a single surgeon through the round window approach using the pull-back technique were included. Our cohort was classified according to the deafness onset (congenital versus postlingual) and the degree of modiolar proximity (less versus tight) with reference to the spiral diameter made by the slim modiolar electrodes in situ on transorbital x ray. We then analyzed the CDL and its metrics using a readily available surgical preplanning tool (OTOPLAN) to obtain comparable data. Results: Among 30 ears associated with congenital deafness, 9 ears (30%) showed less modiolar proximity, while none of the 21 ears from 19 subjects with postlingual deafness exhibited “less modiolar proximity” based on our criteria. In this study, CDL showed significant variation among subjects. Importantly, a significant inverse correlation between spiral diameter and CDL (ρ = −0.581, p < 0.001) was found, showing that shorter CDLs have longer spiral diameter and less modiolar proximity. Moreover, further pull-back technique characterized by pulling out the electrode a little bit more in cases with shorter CDL, if not always, exhibited tighter modiolar proximity. Conclusion: A preponderance of less modiolar proximity of the electrode was observed exclusively among congenital deafness cases, demonstrated by a less tight spiral configuration even under the pull-back technique. Our data suggest that shorter CDL is associated with a less tight spiral configuration of slim modiolar electrodes postoperatively. Depending on the insertion technique, the differential degree of modiolar proximity of slim modiolar electrodes can be alleviated in cases with short CDL, which justifies cochlear duct length-based customized insertion of slim modiolar electrodes.

LMX1A, encoding the LIM homeobox transcription factor, is essential for inner ear development. Despite previous reports of three human LMX1A variants with nonsyndromic hearing loss (NSHL) in the literature, functional characterization of these variants has never been performed. Encouraged by identification of a de novo, heterozygous, missense variant (c.595A > G; p.Arg199Gly) located in the home

No abstract