Variability in Cochlear Implantation Outcomes in a Large German Cohort With a Genetic Etiology of Hearing Loss

Abstract

Objectives: The variability in outcomes of cochlear implantation is largely unexplained, and clinical factors are not sufficient for predicting performance. Genetic factors have been suggested to impact outcomes, but the clinical and genetic heterogeneity of hereditary hearing loss makes it difficult to determine and interpret postoperative performance. It is hypothesized that genetic mutations that affect the neuronal components of the cochlea and auditory pathway, targeted by the cochlear implant (CI), may lead to poor performance. A large cohort of CI recipients was studied to verify this hypothesis. Design: This study included a large German cohort of CI recipients (n = 123 implanted ears; n = 76 probands) with a definitive genetic etiology of hearing loss according to the American College of Medical Genetics (ACMG)/Association for Molecular Pathology (AMP) guidelines and documented postoperative audiological outcomes. All patients underwent preoperative clinical and audiological examinations. Postoperative CI outcome measures were based on at least 1 year of postoperative audiological follow-up for patients with postlingual hearing loss onset (>6 years) and 5 years for children with congenital or pre/perilingual hearing loss onset (≤6 years). Genetic analysis was performed based on three different methods that included single-gene screening, custom-designed hearing loss gene panel sequencing, targeting known syndromic and nonsyndromic hearing loss genes, and whole-genome sequencing. Results: The genetic diagnosis of the 76 probands in the genetic cohort involved 35 genes and 61 different clinically relevant (pathogenic, likely pathogenic) variants. With regard to implanted ears (n = 123), the six most frequently affected genes affecting nearly one-half of implanted ears were GJB2 (21%; n = 26), TMPRSS3 (7%; n = 9), MYO15A (7%; n = 8), SLC26A4 (5%; n = 6), and LOXHD1 and USH2A (each 4%; n = 5). CI recipients with pathogenic variants that influence the sensory nonneural structures performed at or above the median level of speech performance of all ears at 70% [monosyllable word recognition score in quiet at 65 decibels sound pressure level (SPL)]. When gene expression categories were compared to demographic and clinical categories (total number of compared categories: n = 30), mutations in genes expressed in the spiral ganglion emerged as a significant factor more negatively affecting cochlear implantation outcomes than all clinical parameters. An ANOVA of a reduced set of genetic and clinical categories (n = 10) identified five detrimental factors leading to poorer performance with highly significant effects (p < 0.001), accounting for a total of 11.8% of the observed variance. The single strongest category was neural gene expression accounting for 3.1% of the variance. Conclusions: The analysis of the relationship between the molecular genetic diagnoses of a hereditary etiology of hearing loss and cochlear implantation outcomes in a large German cohort of CI recipients revealed significant variabilities. Poor performance was observed with genetic mutations that affected the neural components of the cochlea, supporting the “spiral ganglion hypothesis.”

Embracing digital health: German otolaryngology patients’ usage and prospects of digital information and communication technologies for cross-sectoral care

“…Although numerous recent national and international studies have delved into the utilisation of eHealth for diagnosis and treatment in otolaryngology care, 13 , 21 – 34 the current state and attitudes of otolaryngology patients towards the sustained use of digital ICT, even in the post-CoViD-19 pandemic era, remain insufficiently understood. This knowledge gap raises legitimate concerns that must be further addressed.…”

“…Notably, there was no discernible increase in the adoption or willingness to embrace digital ICT among patients with ear problems despite the recent emphasis of eHealth developments in otolaryngology on this population. 21 – 24 , 28 – 30 , 32 , 50 The overall positive attitude towards the utilisation of online appointment management systems combined with automated reminders, which have already found success in other medical fields and several countries, highlights the considerable potential for increased efficiency in cross-sectoral appointment management and reduced no-show rates. 51 – 53 These findings indicate the appropriateness of introducing these types of eHealth applications in cross-sectoral care throughout the field of otolaryngology.…”

Learning to hear again with alternating cochlear frequency allocations

“…Common theories, such as perceptual learning 20 , Gestalt-psychology, or pattern recognition are limited in explaining how such general auditory skills develop or relate to innate abilities. Nevertheless, CI implanted subjects demonstrate both the remarkable flexibility of the human brain to function adequately with distorted input once it has learned complex pattern recognition during normal language acquisition 21 , as well as the unaccounted variability in performance 22 . Recently, Froemke et al showed in deafened rats that neuromodulation of the locus coeruleus is strongly related to plasticity and directly effects the learning rate with a CI 23 .…”

Tone Decay Reconsidered: Preliminary Results of a Prospective Study in Hearing-Aid Users with Moderate to Severe Hearing Loss

“…Additionally, the nature of poor performance in a CI-fitted population is not yet understood [27]. For example, recent studies [28][29][30] have devoted considerable effort to showing that various factors-including genetic disposition, aetiology, and comorbidities-have an effect on CI outcome. Furthermore, preoperative audiometric assessment in clinical routine [19] potentially provides prognostic value [20][21][22][23].…”