OBJECTIVE:To determine the effect on the frequency of revision surgery caused by electrode migration (EM) in cochlear implantation by use of an electrode fixation clip combined with a novel surgical technique. STUDY DESIGN:Retrospective chart review. SETTING:Tertiary referral center. PATIENTS:The investigated institutional cohort included 1052 cases of cochlear implantation with straight electrode arrays from a single manufacturer between 2011 and 2023. Until 2016, the fixation clip was not used, whereas since 2017, the fixation clip and the described novel surgical technique have been applied as an institutional standard in nearly all cases. INTERVENTION:The titanium electrode fixation clip was first introduced and described in 1998 and was CE marked in Europe in 2014. In modification of the original description, a "Reverse Fixation Clip Technique" was applied to optimize the surgical handling and fixation stability. A similar approach has been described recently. MAIN OUTCOME MEASURE:Cumulative incidence of revision surgery caused by EM. RESULTS:The cumulative incidence of revision surgery caused by EM at 3, 5, and 7 years was 0.5%, 1.0%, and 1.9% in the group without the fixation clip (n=461; 43.4%) and 0.0% at all time points in the group with the fixation clip using the "Reverse Fixation Clip Technique" (n=591; 56.6%) (log-rank test P=0.054). No fixation clip-related complications were noted. CONCLUSION:The application of the fixation clip using the "Reverse Fixation Clip Technique" prevents revision surgery caused by EM in cochlear implantation.

Measuring the electrically evoked stapedius reflex threshold (eSRT) with electromyography (EMG) of the stapedius muscle (SM) may offer an objective approach for cochlear implant (CI) fitting. During unilateral CI surgery in 14 adult patients with single-sided deafness, a retrofacial or anterior approach were used to evaluate the feasibility of SM-EMG during acoustically and electrically elicited stapedius reflex (SR). No adverse events occurred. This neurophysiology-based method was compared with visual detection of the SR. Intraoperatively, the belly of the SM was accessed via the retrofacial approach in 11 patients and via an anterior approach in 3 patients. Objective SR determination using electrical stimulation through the CI combined with SM-EMG was feasible in 7 patients using the retrofacial approach, but in only 1 patient using the anterior approach. Overall, electrical stimulation elicited SM-EMG responses in 8 patients, whereas acoustic stimulation elicited responses in only 3 patients. When eSRT measurement via SM-EMG was possible, stimulation thresholds were equal or slightly lower than thresholds identified visually in 85% of all SR measurements. SM-EMG-based eSRT appears to be a viable approach to estimate the eSRT intraoperatively in CI users as it shows similar performance as current clinical intraoperative standard. Further investigation is needed to investigate the relationship between intraoperative SM-EMG-based eSRT and patients’ comfort levels, establish correction factors, and potentially enable integration into future closed-loop smart CI devices.

HYPOTHESIS:Photon-counting detector CT (PCD-CT) with deep learning-supported denoising can significantly reduce the radiation dose for cochlear implant (CI) planning without compromising the accuracy of cochlear duct length (CDL) measurements. BACKGROUND:Optimal electrode placement in CI surgery requires detailed cochlear anatomy from CT scans, but reducing radiation exposure is critical. This study explores PCD-CT with denoising algorithms to lower doses while preserving diagnostic accuracy. METHODS:Four body donors without inner ear malformations were scanned using PCD-CT at 100%, 50%, 25%, 10%, and 5% dose levels. Images were denoised with ClariAce, a deep learning algorithm, and CDL was measured using OTOPLAN software. Neurotologists compared the results to manual segmentations. Statistical analyses evaluated accuracy across dose levels, with Bland-Altman plots assessing systematic errors. RESULTS:Automatic segmentation succeeded across all doses but showed increased failure below 50%. At 100% and 50% doses, CDL measurements closely matched the gold standard, with minor deviations (eg, -0.17 mm at 50%). Below 50%, CDL underestimation increased (-1.25 mm at 25% and -4.0 mm at 5%). Denoising improved segmentation but minimally affected CDL accuracy at low doses, where manual segmentation performed better. CONCLUSIONS:PCD-CT enables significant dose reduction for CI planning, with reliable CDL accuracy down to 50%. Deep learning denoising enhances image quality but is less effective below 50%, necessitating manual segmentation. These findings align with ALARA principles and suggest further refinement of AI algorithms for lower-dose applicability in CI diagnostics.

Phonation is important for our daily communication and requires the activation of internal and external laryngeal muscles, which can be recorded by electromyography (EMG) using surface or needle electrodes. Here we present a new noncontact method, laryngeal magnetomyography. As a proof-of-concept, we investigated the feasibility of differentiating various vocalization conditions using laryngeal MMG in two healthy subjects using optically pumped magnetometers (OPM). We recorded magnetic muscle activity of the larynx and neighboring cervical muscles using a 3 × 5 array of OPMs. Subjects vocalized an /a/ in three different conditions: loud high pitch, loud low pitch, and soft high pitch, in 90 s blocks. After removing cardiac artifacts, MMG signals were in the range of 1.5 pT with significant amplitude differences between conditions. In both subjects, Linear Discriminant Analysis (LDA) was able to significantly classify vocalization conditions based on the spatial pattern of MMG activities. In sum, we show that laryngeal MMG allows contactless differentiation of phonations based on myomagnetic signals. Our results set the stage for future studies to explore this method for clinical diagnostics and therapy. Functional, contactless muscle recordings during vocalization enable new applications for miniaturized quantum sensors, e.g. in linguistic studies and speech rehabilitation.

Zusammenfassung Hintergrund Hörgeschädigte Menschen mit asymmetrischem Hörverlust und einseitiger Indikation für ein Cochleaimplantat (CI) profitieren in aller Regel deutlich von einer bimodalen Hörversorgung. Der Einfluss dieser Versorgungsart auf das Sprachverstehen (SV) im zeitlichen Verlauf ist bislang nicht hinreichend untersucht. Die vorliegende Studie untersucht den Einfluss einer bimodalen Versorgung auf das SV postlingual ertaubter, bimodal versorgter CI-Träger:innen nach einer Tragedauer von mindestens 36 Monaten und analysiert dabei mögliche Einflussfaktoren. Methode Es wurden 54 bimodal versorgte lautsprachkompetente CI-Träger:innen mit einer CI-Erfahrung von mindestens 36 Monaten in diese retrospektive Längsschnittstudie eingeschlossen. Audiometrische Daten von diesen CI-Träger:innen wurden im zeitlichen Verlauf verglichen. Ergebnisse Die Veränderung der Ergebnisse im Freiburger Einsilbertest (FBE) im Verlauf der 36 Monate war für die Ertaubungsgruppe < 10 Jahre sowohl für den Pegel 65 dB „sound pressure level“ (SPL) als auch für 80 dB SPL signifikant und für die Ertaubungsgruppe ≥ 10 Jahre für 65 dB SPL signifikant ( p < 5 %). Beim Oldenburger Satztest (OlSa) ergab sich für die Konfigurationen S 0 , S 0 N 0 und S 0 N CI eine hochsignifikante Veränderung ( p < 0,1 %). und für S 0 N HG (HG: Hörgerät) eine sehr signifikante Veränderung ( p < 1 %). Das Alter bei Versorgung als möglicher Einflussfaktor konnte durch den FBE nicht bestätigt werden. Die Ertaubungsdauer stellte dagegen einen negativen Einflussfaktor für das SV mit dem CI dar, wobei eine längere Ertaubungsdauer mit schlechteren Ergebnissen beim FBE assoziiert ist. Der Grad der Schwerhörigkeit des mit HG versorgten Ohrs beeinflusste das SV nicht. Im Median betrug der bimodale Nutzen (Differenz aus dem SV mit bimodaler Versorgung gegenüber einseitiger HG-Versorgung beim FBE für 65 dB SPL) über die gesamte Untersuchungszeit 10 %. Für im Median 79 % der Versuchspersonen war der bimodale Nutzen über den gesamten Zeitverlauf von 36 Monaten nachweisbar. Schlussfolgerung Im zeitlichen Verlauf verbessert sich das SV mit dem CI der bimodalen Versuchspersonen signifikant. Die untersuchten Einflussfaktoren (Alter, Ertaubungsdauer und Grad der Schwerhörigkeit des Gegenohrs) unterstützen die leitliniengerechte Indikationsstellung einer bimodalen Versorgung in Deutschland – unabhängig von Alter, Ertaubungsdauer und Hörfähigkeit des Gegenohrs – eine Cochleaimplantation durchzuführen.

Background: Hearing-impaired persons with asymmetric hearing loss and a unilateral indication for a cochlear implant (CI) generally benefit from a bimodal hearing solution. The influence of bimodal fitting on speech comprehension (SC) over time has not yet been sufficiently investigated. The present study examines the influence of bimodal fitting on SC in bimodally fitted CI users with postlingual deafness at least 36 months after implantation and analyzes possible influencing factors. Methods: Included in this retrospective longitudinal study were 54 bimodally fitted speech-competent CI users with at least 36 months of CI experience. Audiometric data of these CI users at predefined timepoints were compared. Results: The change in the results of the Freiburg monosyllabic test (FT) over 36 months was significant (p < 5%) for the deafness group at <10 years for both the 65 dB sound pressure level (SPL) and at 80 dB SPL and also significant for the deafness group >= 10 years for 65 dB SPL. In the Oldenburg sentence test (OlSa) there was a highly significant change (p < 0.1%) for S-0, S0N0, and S0NCI configurations and a very significant change (p < 1%) for S0NHA (HA: hearing aid). Age at implantation as a possible influencing factor could not be confirmed in the FT. In contrast, the duration of deafness was a negative influencing factor for SC with CI in the FT, whereas a longer duration of deafness was associated with worse results in the FT. The degree of hearing loss in the ear fitted with an HA did not influence SC. The median bimodal benefit (here: difference in SC with bimodal fitting compared to unilateral HA fitting for FT at 65 dB SPL) was 10% over the total study period. For a median of 79% of the test subjects, the bimodal benefit was found over the entire period of 36 months. Conclusion: Over time, SC improves significantly with a CI for the bimodal test subjects. The investigated influencing factors (age, duration of deafness, and degree of hearing loss in the contralateral ear) support the indication for bimodal provision in accordance with the guideline in Germany for cochlear implantation-regardless of age, duration of deafness, and hearing ability of the contralateral ear.

Our purpose was to elucidate the genotype and ophthalmological and audiological phenotype in TUBB4B-associated inherited retinal dystrophy (IRD) and sensorineural hearing loss (SNHL), and to model the effects of all possible amino acid substitutions at the hotspot codons Arg390 and Arg391. Six patients from five families with heterozygous missense variants in TUBB4B were included in this observational study. Ophthalmological testing included best-corrected visual acuity, fundus examination, optical coherence tomography, fundus autofluorescence imaging, and full-field electroretinography (ERG). Audiological examination included pure-tone and speech audiometry in adult patients and auditory brainstem response testing in a child. Genetic testing was performed by disease gene panel analysis based on genome sequencing. The molecular consequences of the substitutions of residues 390 and 391 on TUBB4B and its interaction with α-tubulin were predicted in silico on its three-dimensional structure obtained by homology modelling. Two independent patients had amino acid exchanges at position 391 (p.(Arg391His) or p.(Arg391Cys)) of the TUBB4B protein. Both had a distinct IRD phenotype with peripheral round yellowish lesions with pigmented spots and mild or moderate SNHL, respectively. Yet the phenotype was milder with a sectorial pattern of bone spicules in one patient, likely due to a genetically confirmed mosaicism for p.(Arg391His). Three patients were heterozygous for an amino acid exchange at position 390 (p.(Arg390Gln) or p.(Arg390Trp)) and presented with another distinct retinal phenotype with well demarcated pericentral retinitis pigmentosa. All showed SNHL ranging from mild to severe. One additional patient showed a variant distinct from codon 390 or 391 (p.(Tyr310His)), and presented with congenital profound hearing loss and reduced responses in ERG. Variants at codon positions 390 and 391 were predicted to decrease the structural stability of TUBB4B and its complex with α-tubulin, as well as the complex affinity. In conclusion, the twofold larger reduction in heterodimer affinity exhibited by Arg391 substitutions suggested an association with the more severe retinal phenotype, compared to the substitution at Arg390.

Hintergrund Die Ergebnisse mit Cochlea-Implantat (CI) zeigen eine große Variabilität. Der Einfluss bekannter Faktoren wie z.B. die Ertaubungsdauer und das Resthörvermögen liegt bei ca. 20%. Auch eine genetische Diagnose könnte einen Einfluss auf das CI-Ergebnis haben. Die sogenannte “Spiral-Ganglion Hypothese” vermutet einen Zusammenhang zwischen dem Ort einer Genexpression in der Cochlea (sensorisch vs. neuronal) und dem Hörergebnis.

Understanding the genetic basis of hearing loss is becoming increasingly relevant, as 50-70% of congenital hearing loss is hereditary and postlingual hearing loss is also often of hereditary origin. To date, more than 220 genes for hearing loss have been identified and more than 600 syndromes with hearing loss described. This review article explains the classification of genetic hearing loss into syndromic versus non-syndromic forms and the modes of inheritance involved. Some of the most common syndromes (Usher, Pendred, Jervell-Lange-Nielsen, Waardenburg, branchiootorenal, and Alport syndrome) are introductorily described. New sequencing technologies have significantly expanded the diagnostic options for genetic hearing loss and made them more accessible. This text aims to encourage initiation of genetic diagnosis in hearing-impaired patients with suspected hereditary genesis in order to provide the best possible counseling for affected individuals and their families.

Background Outcomes with cochlear implants (CI) show a large variability. The influence of known factors such as duration of deafness and residual hearing is about 20%. A genetic diagnosis could also have an influence on the CI outcome. The so-called "spiral ganglion hypothesis" suspects a relationship between the location of a gene expression in the cochlea (sensory vs. neuronal) and hearing outcome.

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.”

Human stapedius muscle (SM) can be directly and safely accessed via retrofacial approach, opening new approaches to directly measure the electrically evoked stapedius reflex threshold (eSRT). The measurement of the SM activity via direct surgical access represents a potential tool for objective eSRT fitting of cochlear implants (CI), increasing the benefit experienced by the CI users and leading to new perspectives in the development of smart implantable neurostimulators. 3D middle-ear reconstructions created after manual segmentation and related SM accessibility metrics were evaluated before the CI surgery for 16 candidates with assessed stapedius reflex. Retrofacial approach to access the SM was performed after facial recess exposure. In cases of poor exposition of SM, the access was performed anteriorly to the FN via drilling of the pyramidal eminence (PE). The total access rate of the SM via both the retrofacial and anterior approach of the FN was 100%. In 81.2% of cases (13/16), the retrofacial approach allowed to access the SM on previously categorized well exposed (8/8), partially exposed (4/5), and wholly concealed (1/3) SM with respect to FN. Following intraoperative evaluation in the remaining 18.8% (3/16), the SM was accessed anteriorly via drilling of the PE. Exposure of SM with respect to the FN and the sigmoid sinus’s prominence was a predictor for the suitable surgical approach. The retrofacial approach offers feasible and reproducible access to the SM belly, opening direct access to electromyographic sensing of the eSRT. Surgical planner tools can quantitatively assist pre-surgical assessment.

Einleitung Bei erwachsenen Cochlea-Implantat (CI)-Patienten erfolgt die Anpassung durch verbales Feedback, um die Hörschwelle und den angenehmsten Lautstärkepegel (MCL) zu bestimmen. Dieser Ansatz ist für kleine Kinder und Patienten, die nicht mit den Audiologen interagieren können, nicht geeignet. Bei CI-Patienten kann die elektrisch evozierte Stapediusreflexschwelle (ESRT) als Reaktion auf eine elektrische Stimulation mit dem Implantat bestimmt werden. Die ESRT-Messung erfordert keine aktive Mitarbeit der Patienten und kann mit einem Standardtympanometer durchgeführt werden. Diese Art der Messung ist jedoch oft unzuverlässig. Wir haben einen Messaufbau entwickelt, der keinen Druckaufbau im Gehörgang erfordert. Diesen haben wir im Hinblick auf Genauigkeit und Stabilität der Sonde getestet.

Objectives: Hereditary hearing loss exhibits high degrees of genetic and clinical heterogeneity. To elucidate the population-specific and age-related genetic and clinical spectra of hereditary hearing loss, we investigated the sequencing data of causally associated hearing loss genes in a large cohort of hearing-impaired probands with a balanced age distribution from a single center in Southwest Germany. Design: Genetic testing was applied to 305 hearing-impaired probands/families with a suspected genetic hearing loss etiology and a balanced age distribution over a period of 8 years (2011–2018). These individuals were representative of the regional population according to age and sex distributions. The genetic testing workflow consisted of single-gene screening (n = 21) and custom-designed hearing loss gene panel sequencing (n = 284) targeting known nonsyndromic and syndromic hearing loss genes in a diagnostic setup. Retrospective reanalysis of sequencing data was conducted by applying the current American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. Results: A genetic diagnosis was established for 75 (25%) of the probands that involved 75 causal variants in 35 genes, including 16 novel causal variants and 9 medically significant variant reclassifications. Nearly half of the solved cases (47%; n = 35) were related to variants in the five most frequently affected genes: GJB2 (25%), MYO15A, WFS1, SLC26A4, and COL11A1 (all 5%). Nearly one-quarter of the cases (23%; n = 17) were associated with variants in seven additional genes (TMPRSS3, COL4A3, LOXHD1, EDNRB, MYO6, TECTA, and USH2A). The remaining one-third of single cases (33%; n = 25) were linked to variants in 25 distinct genes. Diagnostic rates and gene distribution were highly dependent on phenotypic characteristics. A positive family history of autosomal-recessive inheritance in combination with early onset and higher grades of hearing loss significantly increased the solve rate up to 60%, while late onset and lower grades of hearing loss yielded significantly fewer diagnoses. Regarding genetic diagnoses, autosomal-dominant genes accounted for 37%, autosomal-recessive genes for 60%, and X-linked genes for 3% of the solved cases. Syndromic/nonsyndromic hearing loss mimic genes were affected in 27% of the genetic diagnoses. Conclusions: The genetic epidemiology of the largest German cohort subjected to comprehensive targeted sequencing for hereditary hearing loss to date revealed broad causal gene and variant spectra in this population. Targeted hearing loss gene panel analysis proved to be an effective tool for ensuring an appropriate diagnostic yield in a routine clinical setting including the identification of novel variants and medically significant reclassifications. Solve rates were highly sensitive to phenotypic characteristics. The unique population-adapted and balanced age distribution of the cohort favoring late hearing loss onset uncovered a markedly large contribution of autosomal-dominant genes to the diagnoses which may be a representative for other age balanced cohorts in other populations.

Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss.

Introduction In adult cochlear implant (CI) patients fitting is facilitated by verbal feedback to determine the threshold and most comfortable loudness level (MCL). This approach is not suitable for young children and patients unable to interact with the audiologist. In CI patients, an Electrically Evoked Stapedius Reflex Threshold (ESRT) can be determined in response to electrical stimulation through the implant. ESRT measurement does not require active feedback by the patient and can be obtained through a standard tympanometer. Still, nowadays this type of measurement is often unreliable because of technical shortcomings, which we aim to overcome. We implemented a setting that does not require pressurization of the ear canal and tested it in terms of accuracy and probe stability.

Das Verständnis der genetischen Grundlagen von Schwerhörigkeit ist zunehmend relevant, da 50–70

Alpha-chain collagen molecules encoded by genes that include COL11A1 are essential for skeletal, ocular, and auditory function. COL11A1 variants have been reported in syndromes involving these organ systems. However, a description of the complete clinical spectrum is lacking, as evidenced by a recent association of autosomal dominant nonsyndromic hearing loss due to a splice-altering variant in COL11A1, mapping the DFNA37 locus. Here, we describe two German families presenting prelingual autosomal dominant nonsyndromic hearing loss with novel COL11A1 heterozygous splice-altering variants (c.652-1G>C and c.4338+2T>C) that were molecularly characterized. Interestingly, the c.652-1G>C variant affects the same intron 4 canonical splice site originally reported in the DFNA37 family (c.652-2A>C) but elicits a different splicing outcome. Furthermore, the c.4338+2T>C variant originated de novo. We provide clinical and molecular genetic evidence to unambiguously confirm that COL11A1 splice-altering variants cause DFNA37 hearing loss and affirm that COL11A1 be included in the genetic testing of patients with nonsyndromic deafness.