Cochlear implant electrode design for safe and effective treatment.

The optimal placement of a cochlear implant (CI) electrode inside the scala tympani compartment to create an effective electrode-neural interface is the base for a successful CI treatment. The characteristics of an effective electrode design include (a) electrode matching every possible variation in the inner ear size, shape, and anatomy, (b) electrically covering most of the neuronal elements, and (c) preserving intra-cochlear structures, even in non-hearing preservation surgeries. Flexible electrode arrays of various lengths are required to reach an angular insertion depth of 680° to which neuronal cell bodies are angularly distributed and to minimize the rate of electrode scalar deviation. At the time of writing this article, the current scientific evidence indicates that straight lateral wall electrode outperforms perimodiolar electrode by preventing electrode tip fold-over and scalar deviation. Most of the available literature on electrode insertion depth and hearing outcomes supports the practice of physically placing an electrode to cover both the basal and middle turns of the cochlea. This is only achievable with longer straight lateral wall electrodes as single-sized and pre-shaped perimodiolar electrodes have limitations in reaching beyond the basal turn of the cochlea and in offering consistent modiolar hugging placement in every cochlea. For malformed inner ear anatomies that lack a central modiolar trunk, the perimodiolar electrode is not an effective electrode choice. Most of the literature has failed to demonstrate superiority in hearing outcomes when comparing perimodiolar electrodes with straight lateral wall electrodes from single CI manufacturers. In summary, flexible and straight lateral wall electrode type is reported to be gentle to intra-cochlear structures and has the potential to electrically stimulate most of the neuronal elements, which are necessary in bringing full benefit of the CI device to recipients.

Extracellular Vesicles in Inner Ear Therapies-Pathophysiological, Manufacturing, and Clinical Considerations.

(1) Background: Sensorineural hearing loss is a common and debilitating condition. To date, comprehensive pharmacologic interventions are not available. The complex and diverse molecular pathology that underlies hearing loss may limit our ability to intervene with small molecules. The current review foccusses on the potential for the use of extracellular vesicles in neurotology. (2) Methods: Narrative literature review. (3) Results: Extracellular vesicles provide an opportunity to modulate a wide range of pathologic and physiologic pathways and can be manufactured under GMP conditions allowing for their application in the human inner ear. The role of inflammation in hearing loss with a focus on cochlear implantation is shown. How extracellular vesicles may provide a therapeutic option for complex inflammatory disorders of the inner ear is discussed. Additionally, manufacturing and regulatory issues that need to be addressed to develop EVs as advanced therapy medicinal product for use in the inner ear are outlined. (4) Conclusion: Given the complexities of inner ear injury, novel therapeutics such as extracellular vesicles could provide a means to modulate inflammation, stress pathways and apoptosis in the inner ear.

Bilateral cochlear implantation.

Binaural hearing has certain benefits while listening in noisy environments. It provides the listeners with access to time, level and spectral differences between sound signals, perceived by the two ears. However, single sided deaf (SSD) or unilateral cochlear implant (CI) users cannot experience these binaural benefits due to the acoustic input coming from a single ear. The translational research on bilateral CIs started in the year 1998, initiated by J. Müller and J. Helms from Würzburg, Germany in association with MED-EL. Since then, several clinical studies were conducted by different research groups from across the world either independently or in collaboration with MED-EL. As a result, the bilateral CI has become the standard of care in many countries along with reimbursement by the health care systems. Recent data shows that children particularly, are given high priority for the bilateral CI implantation, most often performed simultaneously in a single surgery, as the binaural hearing has a positive effect on their language development. This article covers the milestones of translational research from the first concept to the widespread clinical use of bilateral CI.

Special electrodes for demanding cochlear conditions.

Optimal matching of an electrode array to the cochlear anatomy plays a key role in bringing the best benefit of CI technology to the users. Even within the category of normal anatomy cochlea, the size variation is huge justifying MED-EL's FLEX electrode array to be available in five different lengths. Within the malformed inner-ear category the anatomical variation is huge, convincing MED-EL to custom-design the electrode array as per the request from the operating surgeons. Thanks to G. Bredberg, M. Beltrame, L. Sennaroglu, J. Gavilan, S. Plontke, T. Lenarz, J. Müller, and few others for their valuable suggestions on unique electrode designs satisfying various needs. Translational research efforts at MED-EL in cooperation with CI surgeons from across the world led to the implantation of a variety of electrode array designs in patients with special cochlear needs.

CI in single-sided deafness.

The cochlear implant (CI) as a treatment option for single-sided deafness (SSD) started with a clinical study looking in to the influence of cochlear implantation with a MED-EL device on incapacitating unilateral tinnitus in SSD. The study began in 2003 and was conducted by P. Van de Heyning and his team in Antwerp, Belgium. The first CI in SSD without tinnitus in Germany was implanted by J. Mueller and R. Jacob in Koblenz in 2005. Translational research activities took place since then to evaluate the CI as a treatment option for SSD not only in adults but also in children. They assessed the hearing performance of SSD patients implanted with CI, importance of long electrode arrays in SSD patients, degree of acceptance of CI by SSD children, importance of early CI implantation in SSD children in developing language skills, music enjoyment by hearing with two ears and evidence on spiral ganglion cell body distribution. In 2013, MED-EL was the first CI manufacturer to receive the CE mark for the indication of SSD and asymmetric hearing loss (AHL) in adults and children. In 2019, MED-EL was the first CI manufacturer to get its CI device approved for patients over the age of five with SSD and AHL, by the FDA in the USA. This article covers the milestones of translational research from the first concept to the widespread clinical use of CI in SSD.

ABI-auditory brainstem implant.

The Auditory Brainstem Implant (ABI) is based on the classic cochlear implant (CI) but uses a different stimulation electrode. At MED-EL, the early development activities on ABI started in the year 1994, with the suggestion coming from J. Helms and J. Müller from Würzburg, Germany in collaboration with the Univ. of Innsbruck Austria. The first ABI surgery in a neuro-fibromatosis (NF2) patient with the MED-EL device took place in the year 1997. Later, the indication of ABI was expanded to non-NF2 patients with severe inner-ear malformation, for whom a regular CI will not be beneficial. Key translational research activities at MED-EL in collaboration with numerous clinics investigating the factors that affect the hearing performance amongst ABI patients, importance of early ABI implantation in children, tools in pre-operative assessment of ABI candidates and new concepts that were pursued with the MED-EL ABI device. The CE-mark for the MED-EL ABI to be used in adults and children down to the age of 12 months without NF-2 was granted in 2017 mainly based on two long-term clinical studies in the pediatric population. This article covers the milestones of translational research from the first concept to the widespread clinical use of ABI in association with MED-EL.

EAS-Combined electric and acoustic stimulation.

Electric-acoustic stimulation (EAS) is a special treatment modality for those patients who are profoundly deaf in the high-frequency (HF) region and retain usable hearing in the low-frequency (LF) region. Combining the electric stimulation with cochlear implant (CI) in the HF and acoustic amplification of residual hearing using a conventional hearing aid (HA) in the LF region defines EAS. The EAS concept was first proposed by C. von Ilberg from Frankfurt, Germany in the year 1997. In association with MED-EL, all the necessary safety studies were performed in non-human subjects before the first patient received it in 1997. In association with MED-EL, all the necessary safety studies were performed in non-human subjects before the first patient received it in 1999. For the patient to successfully use the EAS concept, the residual hearing needs to be preserved to a high extent and for several years. This requires a highly flexible electrode array in safeguarding the intra-cochlear structures during and after the CI electrode array insertion. Combining the HA unit with the audio processor unit of the CI was necessary for the convenient wearing of the unified audio processor. Fitting of the unified audio processor is another important factor that contributes to the overall success of the EAS treatment. The key translational research efforts at MED-EL were on the development of flexible electrodes, a unified audio processor, innovations in the fitting process, intra-operative monitoring of cochlear health during electrode insertion, pre-operative soft-ware tool to evaluate the cochlear size and electrode selection and some new innovations tried within EAS topic. This article covers the milestones of translational research from the first concept to the widespread clinical use of EAS.

Signal processing & audio processors.

Signal processing algorithms are the hidden components in the audio processor that converts the received acoustic signal into electrical impulses while maintaining as much relevant information as possible. Signal processing algorithms should be smart enough to mimic the functionality of external, middle and the inner-ear to provide the cochlear implant (CI) user with a hearing experience as natural as possible. Modern sound processing strategies are based on the continuous interleaved sampling (CIS) strategy proposed by B. Wilson in 1991, which provided envelope information over several intracochlear electrodes. The CIS strategy brought significant gains in speech perception. Translational research activities of MED-EL resulted in further improvements in speech understanding in noisy environments as well as enjoyment of music by not only coding CIS-based envelope information, but by also representing temporal fine structure information in the stimulation patterns of the apical channels. Further developments include "complete cochlear coverage" made possible by deep insertion of the intracochlear electrode, elaborate front end processing, anatomy based fitting (ABF), triphasic pulse stimulation instrumental in the suppression of facial nerve stimulation, and bimodal delay compensation allowing unilateral CI users to experience hearing with hearing aids on the contralateral ear. The large number of hardware developments might be exemplified by the RONDO, the world's first single unit audio processor in 2013. This article covers the milestones of translational research around the signal processing and audio processor topic that took place in association with MED-EL.

Drug delivery in cochlear implantation.

Intra-cochlear fibrous tissue formation around the electrode following cochlear implantation affects the electrode impedance as well as electrode explantation during reimplantation surgeries. Applying corticosteroids in cochlear implantation is one way of minimizing the intra-cochlear fibrous tissue formation around the electrode. It were J. Kiefer, C. von Ilberg, and W. Gstöttner who proposed the first idea on drug delivery application in cochlear implantation to MED-EL in the year 2000. During the twenty years of translational research efforts at MED-EL in collaboration with several clinics and research institutions from across the world, preclinical safety and efficacy of corticosteroids were performed leading to the final formulation of the electrode design. In parallel to the drug eluting CI electrode development, MED-EL also invested research efforts into developing tools enabling delivery of pharmaceutical agents of surgeon's choice inside the cochlea. The inner ear catheter designed to administer drug substances into the cochlea was CE marked in 2020. A feasibility study in human subjects with MED-EL CI featuring dexamethasone-eluting electrode array started in June 2020. This article covers the milestones of translational research towards the drug delivery in CI application that took place in association with MED-EL.

Translational research around five categories of CI.

Five categories of cochlear implants are introduced: The 'classic CI', the 'combined CI' - which can be combining a CI based on electric stimulation with acoustic stimulation (EAS) or with mechanical stimulation (EMS) or with electrical stimulation of the vestibular system (VICI) -, the 'individualised CI', the 'augmented CI' and the 'totally implantable CI'. The translational research activities leading to and within these categories have been, are and will be numerous and are the subject of the compendium for which this paper is the concluding chapter. Early translational research has resulted in the 'classic CI' in 1994. From then on translational research enabled the developments respectively the new indications and reimbursement of CI-systems for bilateral CIs, CI in single sided deafness, the auditory brainstem implant, speech coding and signal processing advances, electrophysiologic measurements for evaluation of cochlear health, all within the classic CI category. Starting points for the four newer categories of CI are either ideas of professionals treating hearing loss or of CI developers. The translational research performed also triggered research that led and leads to improved understanding of the fundamental mechanisms of hearing.

Challenging aspects of contemporary cochlear implant electrode array design.

OBJECTIVE: A design comparison of current perimodiolar and lateral wall electrode arrays of the cochlear implant (CI) is provided. The focus is on functional features such as acoustic frequency coverage and tonotopic mapping, battery consumption and dynamic range. A traumacity of their insertion is also evaluated. METHODS: Review of up-to-date literature. RESULTS: Perimodiolar electrode arrays are positioned in the basal turn of the cochlea near the modiolus. They are designed to initiate the action potential in the proximity to the neural soma located in spiral ganglion. On the other hand, lateral wall electrode arrays can be inserted deeper inside the cochlea, as they are located along the lateral wall and such insertion trajectory is less traumatic. This class of arrays targets primarily surviving neural peripheral processes. Due to their larger insertion depth, lateral wall arrays can deliver lower acoustic frequencies in manner better corresponding to cochlear tonotopicity. In fact, spiral ganglion sections containing auditory nerve fibres tuned to low acoustic frequencies are located deeper than 1 and half turn inside the cochlea. For this reason, a significant frequency mismatch might be occurring for apical electrodes in perimodiolar arrays, detrimental to speech perception. Tonal languages such as Mandarin might be therefore better treated with lateral wall arrays. On the other hand, closer proximity to target tissue results in lower psychophysical threshold levels for perimodiolar arrays. However, the maximal comfort level is also lower, paradoxically resulting in narrower dynamic range than that of lateral wall arrays. Battery consumption is comparable for both types of arrays. CONCLUSIONS: Lateral wall arrays are less likely to cause trauma to cochlear structures. As the current trend in cochlear implantation is the maximal protection of residual acoustic hearing, the lateral wall arrays seem more suitable for hearing preservation CI surgeries. Future development could focus on combining the advantages of both types: perimodiolar location in the basal turn extended to lateral wall location for higher turn locations.

Deep electrode insertion and sound coding in cochlear implants.

Present-day cochlear implants demonstrate remarkable speech understanding performance despite the use of non-optimized coding strategies concerning the transmission of tonal information. Most systems rely on place pitch information despite possibly large deviations from correct tonotopic placement of stimulation sites. Low frequency information is limited as well because of the constant pulse rate stimulation generally used and, being even more restrictive, of the limited insertion depth of the electrodes. This results in a compromised perception of music and tonal languages. Newly available flexible long straight electrodes permit deep insertion reaching the apical region with little or no insertion trauma. This article discusses the potential benefits of deep insertion which are obtained using pitch-locked temporal stimulation patterns. Besides the access to low frequency information, further advantages of deeply inserted long electrodes are the possibility to better approximate the correct tonotopic location of contacts, the coverage of a wider range of cochlear locations, and the somewhat reduced channel interaction due to the wider contact separation for a given number of channels. A newly developed set of strategies has been shown to improve speech understanding in noise and to enhance sound quality by providing a more "natural" impression, which especially becomes obvious when listening to music. The benefits of deep insertion should not, however, be compromised by structural damage during insertion. The small cross section and the high flexibility of the new electrodes can help to ensure less traumatic insertions as demonstrated by patients' hearing preservation rate. This article is part of a Special Issue entitled .

MED-EL Cochlear implants: state of the art and a glimpse into the future.

Cochlear implantation is an accepted treatment method for adults and children with severe to profound hearing loss. Confidence in technology has led to changes in individuals who can receive a cochlear implant and changes in expected benefit with a cochlear implant. This article describes the research and development activities at MED-EL, which make possible the implementation of new speech-coding strategies as well as the application of acoustic and electric stimulation via a combined speech processor in MED-EL devices. Research on benefits from bilateral cochlear implantation and electric-acoustic stimulation are also reviewed. Finally, the potential of drug delivery systems is considered as a way to improve cochlear implant outcomes, and results from preliminary evaluations of a hybrid cochlear implant system with drug delivery capabilities are reported.

Deep electrode insertion in cochlear implants: apical morphology, electrodes and speech perception results.

Morphological examination of the human temporal bone in the apical region supports the benefits of deep electrode insertion. Initiation of spikes on peripheral processes close to the basilar membrane would provide improved channel selectivity during electrical stimulation but recruiting of nerve fibres requires a higher current. A clinical study was performed on 10 users of the MED-EL COMBI 40 + implant to evaluate the effect of the insertion depth of the cochlear implant electrode on speech perception. All subjects were implanted with the standard COMBI 40 + electrode with an insertion depth of > 30 mm. Acute speech tests were carried out in which stimulation was restricted to the apical, middle and basal regions of the cochlea in turn, and using electrode arrangements in which contacts were either distributed over the whole length of the cochlea or concentrated at the basal end, thus mimicking an insertion depth of approximately 20 mm only. The results showed that stimulation of the apical region of the cochlea supports a significant degree of speech understanding, and that distributing the contacts over the whole length of the cochlea improves speech perception in quiet and in noise.