An easy method to determine crucial AMEI performance parameters from clinical routine data in individuals - Part 1: maximum output.

OBJECTIVE: The frequency specific maximum output (MO) of active middle ear implants is the most crucial parameter for speech intelligibility. We determined individual MO from clinical routine data in round window (RW) coupling of the Vibrant Soundbridge (VSB). DESIGN: Monocentric, retrospective analysis. STUDY SAMPLE: 68 ears implanted with the VSB at the RW were analysed. Using bone conduction and direct threshold, MO was determined for combinations of implants (VORP502, VORP503) and processors (Samba, Amadé). Coupling modes were: (A) without coupler (N = 28), (B) spherical coupler (N = 19), (C) soft coupler (N = 10) or (D) custom-made "Hannover coupler" (N = 11). RESULTS: The MO frequency dependence was similar for coupling types (A-D) with a maximum at 1.5 kHz. No differences between groups were observed, although the average MO of the soft coupler was 10 dB lower. The average MO (0.5, 1.0, 2.0, 4.0 kHz) was (A) 77.6 ± 15.0 dB HL, (B) 81.0 ± 11.1 dB HL, (C) 67.6 ± 17.9 dB HL (C), and (D) 79.6 ± 11.7 dB HL (D). CONCLUSION: The individual MO can be determined from patients' clinical data. It permits in-depth analyses of patient outcomes and definition of evidence-based indication and decision criteria.

Does Intraoperative Extracochlear Electrocochleography Correlate With Postoperative Audiometric Hearing Thresholds in Cochlear Implant Surgery? A Retrospective Analysis of Cochlear Monitoring.

In recent years, tools for early detection of irreversible trauma to the basilar membrane during hearing preservation cochlear implant (CI) surgery were established in several clinics. A link with the degree of postoperative hearing preservation in patients was investigated, but patient populations were usually small. Therefore, this study's aim was to analyze data from intraoperative extracochlear electrocochleography (ECochG) recordings for a larger group.During hearing preservation CI surgery, extracochlear recordings were made before, during, and after CI electrode insertion using a cotton wick electrode placed at the promontory. Before and after insertion, amplitudes and stimulus response thresholds were recorded at 250, 500, and 1000 Hz. During insertion, response amplitudes were recorded at one frequency and one stimulus level. Data from 121 patient ears were analyzed.The key benefit of extracochlear recordings is that they can be performed before, during, and after CI electrode insertion. However, extracochlear ECochG threshold changes before and after CI insertion were relatively small and did not independently correlate well with hearing preservation, although at 250 Hz they added some significant information. Some tendencies-although no significant relationships-were detected between amplitude behavior and hearing preservation. Rising amplitudes seem favorable and falling amplitudes disadvantageous, but constant amplitudes do not appear to allow stringent predictions.Extracochlear ECochG measurements seem to only partially realize expected benefits. The questions now are: do gains justify the effort, and do other procedures or possible combinations lead to greater benefits for patients?

Intracochlear Recording of Electrocochleography During and After Cochlear Implant Insertion Dependent on the Location in the Cochlea.

To preserve residual hearing during cochlear implant (CI) surgery it is desirable to use intraoperative monitoring of inner ear function (cochlear monitoring). A promising method is electrocochleography (ECochG). Within this project the relations between intracochlear ECochG recordings, position of the recording contact in the cochlea with respect to anatomy and frequency and preservation of residual hearing were investigated. The aim was to better understand the changes in ECochG signals and whether these are due to the electrode position in the cochlea or to trauma generated during insertion. During and after insertion of hearing preservation electrodes, intraoperative ECochG recordings were performed using the CI electrode (MED-EL). During insertion, the recordings were performed at discrete insertion steps on electrode contact 1. After insertion as well as postoperatively the recordings were performed at different electrode contacts. The electrode location in the cochlea during insertion was estimated by mathematical models using preoperative clinical imaging, the postoperative location was measured using postoperative clinical imaging. The recordings were analyzed from six adult CI recipients. In the four patients with good residual hearing in the low frequencies the signal amplitude rose with largest amplitudes being recorded closest to the generators of the stimulation frequency, while in both cases with severe pantonal hearing losses the amplitude initially rose and then dropped. This might be due to various reasons as discussed in the following. Our results indicate that this approach can provide valuable information for the interpretation of intracochlearly recorded ECochG signals.

First clinical implementation of insertion force measurement in cochlear implantation surgery.

Purpose: The significance of atraumatic electrode array (EA) insertion in cochlear implant (CI) surgery is widely acknowledged, with consensus that forces due to EA insertion are directly correlated with insertion trauma. Unfortunately, the manual perception of these forces through haptic feedback is inherently limited, and techniques for in vivo force measurements to monitor the insertion are not yet available. Addressing this gap, we developed of a force-sensitive insertion tool capable of capturing real-time insertion forces during standard CI surgery. Methods: This paper describes the tool and its pioneering application in a clinical setting and reports initial findings from an ongoing clinical study. Data and experiences from five patients have been evaluated so far, including force profiles of four patients. Results: The initial intraoperative experiences are promising, with successful integration into the conventional workflow. Feasibility of in vivo insertion force measurement and practicability of the tool's intraoperative use could be demonstrated. The recorded in vivo insertion forces show the expected rise with increasing insertion depth. Forces at the end of insertion range from 17.2 mN to 43.6 mN, while maximal peak forces were observed in the range from 44.8 mN to 102.4 mN. Conclusion: We hypothesize that this novel method holds the potential to assist surgeons in monitoring the insertion forces and, thus, minimizing insertion trauma and ensuring better preservation of residual hearing. Future data recording with this tool can form the basis of ongoing research into the causes of insertion trauma, paving the way for new and improved prevention strategies.

A New Methodology for Evaluation of Large Vestibular Aqueduct in CT and MRI Images.

HYPOTHESIS: Development of a new method for large vestibular aqueduct (LVA)/large endolymphatic sac anomaly (LESA) assessment using magnetic resonance imaging (MRI) and computed tomography (CT)/cone beam CT (CBCT) images. The secondary objective was to compare both modalities. BACKGROUND: The gold standard for LVA diagnosis is the analysis of CT images using Valvassori and Clemis or Cincinnati criteria. The previous studies showed inconclusive results regarding the correlation between audiological and radiological data. METHODS: Retrospective analysis of radiological images from 173 patients (315 ears), who were diagnosed with LVA/LESA based on CT/CBCT and/or MRI images of the temporal bone. The images obtained using both techniques were used to measure the following dimensions of vestibular aqueduct (VA)/endolymphatic duct (ED)/intraosseous endolymphatic sac (ES): width of the opening, length, and width at external aperture. In MRI images, the maximal contact diameters of the extraosseous or intraosseous ES and dura mater were measured as well. RESULTS: LVA has been reported to be bilateral in 82% (142 patients) and unilateral in 18% (31 patients) of cases. Comparison of MRI and CT/CBCT measurements showed a moderate correlation (0.64) in external aperture, a moderate correlation (0.57) in the width of the VA opening, and a weak correlation (0.34) in length measurements (p < 0.05). CONCLUSION: We developed a new method to identify the heterogeneous pathology of LVA/LESA using reconstruction along the VA/ED/intraosseous ES axis, three measurements on two planes, and focus on the maximal contact diameter between the extraosseous or intraosseous ES and dura mater.

Physical Trace Gas Identification with the Photo Electron Ionization Spectrometer (PEIS).

Chemosensor technology for trace gases in the air always aims to identify these compounds and then measure their concentrations. For identification, traceable methods are sparse and relate to large appliances such as mass spectrometers. We present a new method that uses the alternative traceable measurement of the ionization energies of trace gases in a way that can be miniaturized and energetically tuned. We investigate the achievable performance. Since tunable UV sources are not available for photoionization, we take a detour via impact ionization with electrons, which we generate using the photoelectric effect and bring to sharp, defined energies on a nanoscale in the air. Electron impact ionization is thus possible at air pressures of up to 900 hPa. The sensitivity of the process reaches 1 ppm and is equivalent to that of classic PID. With sharpened energy settings, substance identification is currently possible with an accuracy of 30 meV. We can largely explain the experimental observations with the known quantum mechanical models.

Development of a feline model for preclinical research of a new translabyrinthine auditory nerve implant.

Cochlear implants are among the most successful neural prosthetic devices to date but exhibit poor frequency selectivity and the inability to consistently activate apical (low frequency) spiral ganglion neurons. These issues can limit hearing performance in many cochlear implant patients, especially for understanding speech in noisy environments and in perceiving or appreciating more complex inputs such as music and multiple talkers. For cochlear implants, electrical current must pass through the bony wall of the cochlea, leading to widespread activation of auditory nerve fibers. Cochlear implants also cannot be implanted in some individuals with an obstruction or severe malformations of the cochlea. Alternatively, intraneural stimulation delivered via an auditory nerve implant could provide direct contact with neural fibers and thus reduce unwanted current spread. More confined current during stimulation can increase selectivity of frequency fiber activation. Furthermore, devices such as the Utah Slanted Electrode Array can provide access to the full cross section of the auditory nerve, including low frequency fibers that are difficult to reach using a cochlear implant. However, further scientific and preclinical research of these Utah Slanted Electrode Array devices is limited by the lack of a chronic large animal model for the auditory nerve implant, especially one that leverages an appropriate surgical approach relevant for human translation. This paper presents a newly developed transbullar translabyrinthine surgical approach for implanting the auditory nerve implant into the cat auditory nerve. In our first of a series of studies, we demonstrate a surgical approach in non-recovery experiments that enables implantation of the auditory nerve implant into the auditory nerve, without damaging the device and enabling effective activation of the auditory nerve fibers, as measured by electrode impedances and electrically evoked auditory brainstem responses. These positive results motivate performing future chronic cat studies to assess the long-term stability and function of these auditory nerve implant devices, as well as development of novel stimulation strategies that can be translated to human patients.

Correlation of Scalar Cochlear Volume and Hearing Preservation in Cochlear Implant Recipients with Residual Hearing.

OBJECTIVE: Preservation of residual hearing is one of the main goals in cochlear implantation. There are many factors that can influence hearing preservation after cochlear implantation. The purpose of the present study was to develop an algorithm for validated preoperative cochlear volume analysis and to elucidate the role of cochlear volume in preservation of residual hearing preservation after atraumatic cochlear implantation. STUDY DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENTS: A total of 166 cochlear implant recipients were analyzed. All patients were implanted with either a MED-EL (Innsbruck, Austria) FLEXSOFT (n = 3), FLEX28 (n = 72), FLEX26 (n = 1), FLEX24 (n = 41), FLEX20 (n = 38), or FLEX16 (n = 11, custom made device) electrode array through a round window approach. Main outcome measures: Cochlear volume as assessed after manual segmentation of cochlear cross-sections in cone beam computed tomography, and preservation of residual hearing 6 months after implantation were analyzed. The association between residual hearing preservation and cochlear volume was then assessed statistically. RESULTS: Rapid and valid cochlear volume analysis was possible using the individual cross-sections and a newly developed and validated algorithm. Cochlear volume had the tendency to be larger in patients with hearing preservation than in those with hearing loss. Significant correlations with hearing preservation could be observed for the basal width and length of the basal turn. CONCLUSIONS: Preservation of residual hearing after cochlear implantation may depend on cochlear volume but appears to be influenced more strongly by other cochlear dimensions.

On the interdependence of insertion forces, insertion speed, and lubrication: Aspects to consider when testing cochlear implant electrodes.

OBJECTIVES: During the insertion of cochlear implant (CI) electrode arrays, forces occur which may cause trauma and poorer hearing outcomes. Unfortunately, research groups investigating factors influencing insertion forces come to contradicting results, especially regarding insertion speed. This study was conducted to investigate the origin of these contradicting results and to determine how different testing conditions influence experimental findings. METHODS: Repeated, automated insertions with three different FLEX28 CI electrode arrays (MED-EL, Innsbruck, Austria) were performed into a newly developed, anatomically correct and 3D-printed mean scala tympani phantom. The testing protocol for each electrode included variations in insertion speed (v = 0.1-2.0 mm/s) and lubrication (90%, 50%, and 10% liquid soap), resulting in 51 insertions per electrode array and a total of 153 insertions. RESULTS: The test setup and protocol allowed for repeatable insertions with only minimal change in the morphology of the insertion force profiles per testing condition. Strong but varying dependencies of the maximal insertion forces and work were found regarding both lubrication and speed: work-speed dependency is constant for the 10% lubricant, negative for the 50% lubricant and positive for the 90% lubricant. CONCLUSION: Our results can explain part of the contradicting results found within previous studies by translating interrelations known from lubricated rubber friction to the field of CI electrode array insertion. We show that the main driver behind measured bulk forces are most likely the generated friction forces, which are strongly dependent on insertion speed and lubrication. The employed test setup allows for conducting repeatable and comparable insertion studies, which can be recapitulated by other centers due to the detailed explanation of the test setup as well as the developed and freely available insertion phantom. This study hence represents another important step toward standardizing CI array insertion testing.

Variability in Receptive Language Development Following Bilateral Cochlear Implantation.

OBJECTIVES: The primary aim was to investigate the variability in language development in children aged 5-7.5 years after bilateral cochlear implantation (CI) up to the age of 2 years, and any impact of the age at implantation and additional noncognitive or anatomical disorders at implantation. DESIGN: Data of 84 congenitally deaf children that had received simultaneous bilateral CI at the age of ≤ 24 months were included in this retrospective study. The results of language comprehension acquisition were evaluated using a standardized German language acquisition test for normal hearing preschoolers and first graders. Data on speech perception of monosyllables and sentences in quiet and noise were added. RESULTS: In a monosyllabic test, the children achieved a median performance of 75.0 ± 12.88%. In the sentence test in quiet, the median performance was 89 ± 12.69%, but dropped to 54 ± 18.92% in noise. A simple analysis showed a significant main effect of age at implantation on monosyllabic word comprehension (p < .001), but no significant effect of comorbidities that lacked cognitive effects (p = .24). Language acquisition values correspond to the normal range of children with normal hearing. Approximately 25% of the variability in the language acquisition tests is due to the outcome of the monosyllabic speech perception test. CONCLUSIONS: Congenitally deaf children who were fitted bilaterally in the 1st year of life can develop age-appropriate language skills by the time they start school. The high variability in the data is partly due to the age of implantation, but additional factors such as cognitive factors (e.g., working memory) are likely to influence the variability.

Long-Term Hearing Outcome of Cochlear Implantation in Cases with Simultaneous Intracochlear Schwannoma Resection.

OBJECTIVES: The aim was to analyze the long-term hearing results after simultaneous microsurgical extirpation via enlarged cochleostomy and cochlear implantation in intracochlear schwannoma as compared with non-tumor single-side deafness patients. METHODS: Microsurgical extirpation via enlarged cochleostomy with simultaneous cochlear implantation was performed in 15 cases of intracochlear schwannoma between 2014 and 2021. Speech recognition tests in German language and impedance performances were collected over 36 months of observation and compared with an internal cohort of 52 age matched non-tumor single-side deafness patients. Retrospective cohort study in a tertiary referral center. RESULTS: The surgery proved feasible and uneventful in all cases. In the case of intracochlear schwannoma, the hearing rehabilitation results were highly satisfactory and comparable to those of the non-tumor single-side deafness cohort. The speech recognition performance improved steadily in the first 12 months; afterward, it remained stable, providing indirect evidence against tumor recurrence during the follow-up. One patient required implant revision surgery related to device failure, but no recurrence was registered in the 36 months of observation. CONCLUSIONS: Cochlear implantation is the strategy of choice for hearing rehabilitation in case of intracochlear schwannomas in the long term. In particular, the combination of tumor extirpation via cochleostomy with a cochlear implantation in the same surgical time offers a viable therapy for intracochlear schwannoma, granting a sufficient degree of radicality without compromising the cochlear integrity. This technique allows for revision surgery if required. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1854-1860, 2024.

A Novel Method to Determine the Maximum Output of Individual Patients for an Active Transcutaneous Bone Conduction Implant Using Clinical Routine Data.

OBJECTIVES: The maximum output provided by a bone conduction (BC) device is one of the main factors that determines the success when treating patients with conductive or mixed hearing loss. Different approaches such as sound pressure measurements using a probe microphone in the external auditory canal or a surface microphone on the forehead have been previously introduced to determine the maximum output of active transcutaneous BC devices that are not directly accessible after implantation. Here, we introduce a method to determine the maximum output hearing level (MOHL) of a transcutaneous active BC device using patients' audiometric data. DESIGN: We determined the maximum output in terms of hearing level MOHL (dB HL) of the Bonebridge using the audiometric and direct BC threshold of the patient together with corresponding force levels at hearing threshold and the maximum force output of the device. Seventy-one patients implanted with the Bonebridge between 2011 and 2020 (average age 45 ± 19 years ranging from 5 to 84 years) were included in this study. The analyses of MOHLs were performed by (1) dividing patients into two groups with better or worse average audiometric BC threshold (0.5, 1, 2, 4 kHz), on the ipsilateral side or (2) by separating the MOHLs based on better or worse frequency-by-frequency specific audiometric BC thresholds on the ipsilateral (implanted) side. RESULTS: When using a frequency-by-frequency analysis obtained average ipsilateral MOHLs were in the range between 51 and 73 dB HL for frequencies from 0.5 to 6 kHz in the group with better audiometric BC threshold on the ipsilateral ears. The average contralateral MOHLs in the group with better contralateral hearing were in the range from 43 to 67 dB HL. The variability of the data was approximately 6 to 11 dB (SDs) across measured frequencies (0.5 to 6 kHz). The average MOHLs were 4 to 8 dB higher across frequencies in the group with better audiometric BC threshold on the ipsilateral ears than in the group with better audiometric BC threshold on the contralateral ears. The differences between groups were significant across measured frequencies ( t test; p < 0.05). CONCLUSIONS: Our proposed method demonstrates that the individual frequency-specific MOHL on the ipsilateral and contralateral side of individual patients with a transcutaneous BC device can be determined mainly using direct and audiometric BC threshold data of the patients from clinical routine. The average MOHL of the implant was found 4 to 8 dB higher on the ipsilateral (implanted) side than on the contralateral side.

Short-term safety and effectiveness of the mCLIP partial prosthesis.

PURPOSE: This multicentric, retrospective study aimed to analyze the short-term safety and effectiveness of the mCLIP Partial Prosthesis. METHODS: Patients underwent tympanoplasty with implantation of a mCLIP Partial Prosthesis. Follow-up examination included ear microscopy and pure-tone audiometry to determine the post-operative pure tone average of the frequencies 0.5, 1, 2 and 3 kHz (PTA4). The post-operative PTA4 air bone gap (ABG) was used to evaluate the audiological outcome. A post-operative minimum and maximum follow-up period was not defined. Thus, the follow-up times of each study center were different, which resulted in different follow-up times for the audiological analysis and for adverse events (AE). RESULTS: 72 (66 adults, 6 children) patients were implanted with the mCLIP Partial Prosthesis. 68 (62 adults, 6 children) patients underwent audiological examination; all 72 patients were examined for adverse events. All patients (N = 68): 72.1% of the patients showed a PTA4 ABG of ≤ 20 dB. Individual post-operative bone conduction (BC) PTA4 thresholds were stable in 67 patients. The mean post-operative follow-up time was 78 ± 46 days. Children (N = 6): 5 out of 6 children showed a PTA4 ABG of ≤ 20 dB. None of the children reported a BC PTA4 deterioration of > 10 dB HL after the implantation. The mean post-operative follow-up time was 101 ± 45 days. Adverse events (all patients, N = 72): 15 (14 adults, 1 child) patients had AEs (27 AEs and 2 Follow-Ups). The mean post-operative follow-up time was 375 days. CONCLUSION: Clinical data show satisfactory audiological parameters after implantation of the mCLIP Partial Prosthesis. The prosthesis is safe and effective for implantation in children and adults. TRIAL REGISTRATION NUMBER: NCT05565339, 09 September 2022, retrospectively registered.

Cochlear Implant Stimulation Parameters Play a Key Role in Reducing Facial Nerve Stimulation.

A percentage (i.e., 5.6%) of Cochlear Implant (CI) users reportedly experience unwanted facial nerve stimulation (FNS). For some, the effort to control this problem results in changing stimulation parameters, thereby reducing their hearing performance. For others, the only viable solution is to deactivate the CI completely. A growing body of evidence in the form of case reports suggests that undesired FNS can be effectively addressed through re-implantation with an Oticon Medical (OM) Neuro-Zti implant. However, the root of this benefit is still unknown: is it due to surgical adjustments, such as varied array geometries and/or positioning, or does it stem from differences in stimulation parameters and/or grounding? The OM device exhibits two distinct features: (1) unique stimulation parameters, including anodic leading pulses and loudness controlled by pulse duration-not current-resulting in lower overall current amplitudes; and (2) unconventional grounding, including both passive (capacitive) discharge, which creates a pseudo-monophasic pulse shape, and a 'distributed-all-polar' (DAP) grounding scheme, which is thought to reduce current spread. Unfortunately, case reports alone cannot distinguish between surgical factors and these implant-related ones. In this paper, we present a novel follow-up study of two CI subjects who previously experienced FNS before re-implantation with Neuro-Zti implants. We used the Oticon Medical Research Platform (OMRP) to stimulate a single electrode in each subject in two ways: (1) with traditional monopolar biphasic cathodic-first pulses, and (2) with distinct OM clinical stimulation. We progressively increased the stimulation intensity until FNS occurred or the sound became excessively loud. Non-auditory/FNS sensations were observed with the traditional stimulation but not with the OM clinical one. This provides the first direct evidence demonstrating that stimulation parameters and/or grounding-not surgical factors-play a key role in mitigating FNS.

Deep intracochlear injection of triamcinolone-acetonide with an inner ear catheter in patients with residual hearing.

Introduction: In a previous study, an inner ear catheter was used to deliver low- and high-dose steroids into the cochlea prior to cochlear implant electrode insertion. With this approach, more apical regions of the cochlea could be reached and a reduction of electrode impedances in the short term was achieved in cochlear implant recipients. Whether intracochlear application of drugs via the catheter is a safe method also for patients with residual hearing has not been investigated hitherto. The aim of the present study was therefore to investigate the effect of intracochlear triamcinolone application in cochlear implant recipients with residual hearing. Patients and methods: Patients with residual hearing were administered triamcinolone-acetonide (4 mg/ml; n = 10) via an inner ear catheter just prior to insertion of a MED-EL FLEX28 electrode. Impedances were measured at defined time points (intra-operatively, post-operatively and at first fitting) and retrospectively compared with a control group (no steroid application) and low- and high-dose group. Hearing thresholds were measured preoperatively, 3 days after surgery and at first fitting by pure tone audiometry. Pre- to postoperative hearing loss was determined at first fitting and compared to results from a previous study. Results: The median hearing loss after implantation (125-1,500 Hz) was 20.6 dB. Four patients (40%) showed a median hearing loss of less than 15 dB, three patients (30%) between 15 and 30 dB and three patients (30%) more than 30 dB. The median hearing loss was similar to the results obtained from our previous study showing a median hearing loss of 24 dB when using FLEX28 electrode arrays. Conclusion: No difference in residual hearing loss was found when comparing application of triamcinolone-acetonide using an inner ear catheter prior to the insertion of a FLEX28 electrode array to the use of the FLEX28 electrode array without the catheter. Thus, we conclude that application of drugs to the cochlea with an inner ear catheter could be a feasible approach in patients with residual hearing.

Correlation Between Air-Bone Gap and Vestibular Aqueduct Size in Enlarged Vestibular Aqueduct Syndrome: A Systematic Review.

The purpose of this review was to evaluate the air-bone gap with vestibular aqueduct size in enlarged vestibular aqueduct syndrome. According to the PRISMA guidelines we conducted a systematic review of the literature. Published international articles in English from 2000 to 2022 were screened, checking for studies that evaluated the air-bone gap of patients affected by enlarged vestibular aqueduct syndrome and the size of vestibular aqueduct. Data related to the hearing assessment and imaging investigation of enrolled participants were extracted. The chosen primary outcome measure was the correlation between air-bone-gap and vestibular aqueduct size. The database search allowed us to screen 485 articles and to select 5 articles discussing this topic for a total of 349 patients. Two studies showed a positive correlation between air-bone gap and vestibular aqueduct size, one only a trend and two no correlation. To date, it is not possible to draw conclusions whether or not there is a positive correlation between air-bone gap and vestibular aqueduct size in enlarged vestibular aqueduct syndrome. Higher quality studies would be conducted with standardized outcome measures to clarify the specific research question.

"Of mice and men": the relevance of Cometin and Erythropoietin origin for its effects on murine spiral ganglion neuron survival and neurite outgrowth in vitro.

Neurotrophic factors (NTF) play key roles in the survival of neurons, making them promising candidates for therapy of neurodegenerative diseases. In the case of the inner ear, sensorineural hearing loss (SNHL) is characterized over time by a degeneration of the primary auditory neurons, the spiral ganglion neurons (SGN). It is well known that selected NTF can protect SGN from degeneration, which positively influences the outcome of cochlear implants, the treatment of choice for patients with profound to severe SNHL. However, the outcome of studies investigating protective effects of NTF on auditory neurons are in some cases of high variability. We hypothesize that the factor origin may be one aspect that affects the neuroprotective potential. The aim of this study was to investigate the neuroprotective potential of human and mouse Erythropoietin (EPO) and Cometin on rat SGN. SGN were isolated from neonatal rats (P 2-5) and cultured in serum-free medium. EPO and Cometin of mouse and human origin were added in concentrations of 0.1, 1, and 10 ng/mL and 0.1, 1, and 10 µg/mL, respectively. The SGN survival rate and morphology, and the neurite outgrowth were determined and compared to negative (no additives) and positive (brain-derived neurotrophic factor, BDNF) controls. A neuroprotective effect of 10 µg/mL human Cometin comparable to that obtained with BDNF was observed in the SGN-culture. In contrast, mouse Cometin was ineffective. A similar influence of 10 µg/mL human and mouse and 1 µg/mL human Cometin on the length of regenerated neurites compared to BDNF was also detected. No other Cometin-conditions, and none of the EPO-conditions tested had neuroprotective or neuritogenic effects or influenced the neuronal morphology of the SGN. The neuroprotective effect of 10 µg/mL human Cometin on SGN indicates it is a potentially interesting protein for the supportive treatment of inner ear disorders. The finding that mouse Cometin had no effect on the SGN in the parallel-performed experiments underlines the importance of species origin of molecules being screened for therapeutic purpose.

The Dependency of Cochlear Lateral Wall Measurements on Observer and Imaging Type.

HYPOTHESIS: Assessment techniques for the cochlear spatial lateral wall are associated with inter-rater variability, but derived clinical recommendations nonetheless offer value for individualized electrode selection. BACKGROUND: Anatomical variations influence the location of cochlear implant electrodes inside the cochlea. Preoperative planning allows individualization of the electrode based on characterization of the bony lateral wall. METHODS: The study used publicly available digitized temporal bones based on microslicing and computed tomography. Four experienced observers assessed the lateral wall applying manual tracing, linear regression scaling and elliptic-circular approximation methods in all modalities. Radial and height differences were computed in 90-degree steps from the round window center to the apex. Total length, total angular length, and tonotopic frequencies were computed for each reconstruction. RESULTS: Differences were found most pronounced between assessment methods in vertical direction across observers and imaging modalities. One of the five anatomies was consistently found to be of shorter cochlear duct length with estimation techniques yielding more conservative results compared with manual tracings. CONCLUSIONS: Assessment techniques for the bony lateral wall yield method, observer, and image modality related deviations. Automation of the anatomical characterization may offer potential in minimizing inaccuracies. Nonetheless, observers were consistently able to detect a smaller inner ear demonstrating the ability of current methods to contribute to an optimized choice of electrodes based on individual patient anatomy.

Cochlear coverage with lateral wall cochlear implant electrode arrays affects post-operative speech recognition.

OBJECTIVES: The goal was to investigate the relationship between the insertion angle/cochlear coverage of cochlear implant electrode arrays and post-operative speech recognition scores in a large cohort of patients implanted with lateral wall electrode arrays. METHODS: Pre- and post-operative cone beam computed tomography scans of 154 ears implanted with lateral wall electrode arrays were evaluated. Traces of lateral wall and electrode arrays were combined into a virtual reconstruction of the implanted cochlea. This reconstruction was used to measure insertion angles and proportional cochlear coverage. Word recognition scores and sentence recognition scores measured 12 months after implantation using electric-only stimulation were used to examine the relationship between cochlear coverage/insertion angle and implantation outcomes. RESULTS: Post-operative word recognition scores and the difference between post- and pre-operative word recognition scores were positively correlated with both cochlear coverage and insertion angle, however sentence recognition scores were not. A group-wise comparison of word recognition scores revealed that patients with cochlear coverage below 70% performed significantly worse than patients with coverage between 79%-82% (p = 0.003). Performance of patients with coverage above 82% was on average poorer than between 79%-82, although this finding was not statistically significant (p = 0.84). Dividing the cohort into groups based on insertion angle quadrants revealed that word recognition scores were highest above 450° insertion angle, sentence recognition scores were highest between 450° and 630° and the difference between pre- and post-operative word recognition scores was largest between 540° and 630°, however none of these differences reached statistical significance. CONCLUSIONS: The results of this study show that cochlear coverage has an effect on post-operative word recognition abilities and the benefit patients receive from their implant. Generally, higher coverage led to better outcomes, however there were results indicating that insertion past 82% cochlear coverage may not provide an additional benefit for word recognition. These findings can be useful for choosing the optimal electrode array and thereby improving cochlear implantation outcomes on a patient-individual basis.

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

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."