Gerrit Paasche

Temporal Bone Results and Hearing Preservation with a New Straight Electrode

Due to improved technology, cochlear implant (CI) candidacy has been widened towards patients with usable residual hearing in the low frequency range. These patients might benefit from additional acoustic amplification provided that residual hearing can be preserved with cochlear implantation. To provide a high probability of hearing preservation, a new electrode array was designed and developed at the Medizinische Hochschule Hannover. This ‘Hybrid-L’ electrode array has 22 electrodes spread over 15 mm with an overall insertion depth of 16 mm. The straight electrode with modiolus facing contacts is designed for a round window insertion. It shall provide the full range of the currently most advanced Nucleus CI system. A temporal bone study demonstrated the favorable insertion characteristics and minimized trauma to intracochlear structures. Compared to standard CI electrodes especially no basilar membrane perforation could be found. So far, 4 patients have been implanted and residual hearing could be preserved. One patient was fitted and showed a marked additional benefit from the electroacoustic stimulation compared to either acoustic or electrical stimulation alone. These results are very encouraging towards a concept of reliable hearing preservation with cochlear implantation.

Evaluation of the Advance Off-Stylet Insertion Technique and the Cochlear Insertion Tool in Temporal Bones:

Objective: The concept and design of new cochlear implant electrodes is a challenging process. To evaluate new electrode designs, we present a study that uses a microgrinding procedure to evaluate damage to the microstructures of the cochlea resulting from the insertion procedure. In this study, we compared different insertion techniques with the Contour electrode with Softip for placement inside the cochlea and any resulting damage. Methods: Twenty-five fresh frozen human temporal bones were used to compare electrode insertion characteristics with three insertion techniques (i.e., conventional insertion, Advance Off-Stylet performed manually, and Advance Off-Stylet performed with insertion tool) and two prototype variants of the Contour electrode with Softip (referred as Softip I and Softip II in this article). Five temporal bones were used for each arm of the study: Softip I electrode and conventional insertion; Softip I electrode and manual Advance Off-Stylet insertion; Softip I electrode and Advance Off-Stylet insertion with an early experimental insertion tool; Softip II prototype electrode and manual Advance Off-Stylet insertion; and Softip II prototype and Advance Off-Stylet insertion with a prototype insertion tool. The temporal bones were dehydrated and embedded in epoxy and used for the microgrinding procedure. Resulting images were documented and compared with conventional radiographic images. Results: Our results showed that, especially when using the conventional insertion technique with Softip I electrode arrays, basilar membrane perforations were observable. Using the prototype insertion tool, good placement of the electrode array but also two basilar membrane perforations (one with each type of electrode) were observed. In contrast, the Advance Off-Stylet insertion technique did not show basilar membrane perforation with Softip I and II electrodes and resulted in reliable perimodiolar placement of the arrays. Conclusion: Using microgrinding of temporal bones, the Advance Off-Stylet insertion technique was proven to enable more atraumatic insertions of Contour electrodes with Softip and to provide very reliable perimodiolar placements.

Changes of postoperative impedances in cochlear implant patients: the short-term effects of modified electrode surfaces and intracochlear corticosteroids.

Objective: The objective of this study was to investigate the effect of intraoperative application of steroid suspension and coating of the electrode contacts with a thin film of iridium oxide on the short-term, time-dependent development of the intracochlear impedance in adults implanted with the Nucleus 24 Contour electrode. Study Design: The time-dependent development of intracochlear impedances was investigated in four different groups of adult patients at daily and later weekly intervals until the first fitting. The four groups were as follows: 1) standard Nucleus 24 Contour (control, n = 7); 2) standard Nucleus 24 Contour with intraoperative application of steroids (Group S, n = 6); 3) iridium-coated Nucleus 24 Contour control (Group I, n = 8); and 4) iridium-coated Nucleus 24 Contour with intraoperative application of steroids (Group I + S, n = 5). All patients had postlinguistic onset of severe to profound sensorineural hearing loss and no or little benefit of conventional hearing aids. Absence of ossification or any other cochlear anomaly and also absence of signs of retrocochlear or central origin to the hearing impairment bilaterally had to be confirmed preoperatively. Results: Steroid application reduced impedances significantly (Groups S and I + S), whereas iridium coating lowered variance of the impedance among patients but did not reduce the impedance significantly. The steroid-induced reduction is more pronounced at basal electrode contacts. Furthermore, there is some indication that the tissue growth could be faster in patients having the iridium-coated Contour electrode. Conclusion: Provided that the reduction of electrode impedances with application of steroids is persisting, intracochlear application of steroids can be considered on a regular basis. Iridium coating of the electrode contacts seems not to be justified to be included as standard procedure.

Effects of delayed treatment with combined GDNF and continuous electrical stimulation on spiral ganglion cell survival in deafened guinea pigs.

Electrical stimulation (ES) of spiral ganglion cells (SGC) via a cochlear implant is the standard treatment for profound sensor neural hearing loss. However, loss of hair cells as the morphological correlate of sensor neural hearing loss leads to deafferentation and death of SGC. Although immediate treatment with ES or glial cell line–derived neurotrophic factor (GDNF) can prevent degeneration of SGC, only few studies address the effectiveness of delayed treatment. We hypothesize that both interventions have a synergistic effect and that even delayed treatment would protect SGC. Therefore, an electrode connected to a pump was implanted into the left cochlea of guinea pigs 3 weeks after deafening. The contralateral untreated cochleae served as deafened intraindividual controls. Four groups were set up. Control animals received intracochlear infusion of artificial perilymph (AP/−). The experimental groups consisted of animals treated with AP in addition to continuous ES (AP/ES) or treated with GDNF alone (GDNF/−) or GDNF combined with continuous ES (GDNF/ES). Acoustically and electrically evoked auditory brain stem responses were recorded. All animals were killed 48 days after deafening; their cochleae were histologically evaluated. Survival of SGC increased significantly in the GDNF/− and AP/ES group compared with the AP/− group. A highly significant increase in SGC density was observed in the GDNF/ES group compared with the control group. Additionally, animals in the GDNF/ES group showed reduced EABR thresholds. Thus, delayed treatment with GDNF and ES can protect SGC from degeneration and may improve the benefits of cochlear implants.

The long-term effects of modified electrode surfaces and intracochlear corticosteroids on postoperative impedances in cochlear implant patients.

Objective: The objective of this study was to investigate the long-term effect of intraoperative application of steroid suspension and coating of the electrode contacts with a thin film of iridium oxide on the intracochlear impedance development after cochlear implantation and on the impedance difference before and after stimulation. Design: Time-dependent development of intracochlear impedances was investigated in 4 different groups of adult patients up to 4 years after implantation. Additionally, during rehabilitation period just after first fitting, impedances before and after stimulation were measured as to investigate the influence of electrical stimulation on the impedances. Results from standard Nucleus 24 Contour (control), standard Nucleus 24 Contour with intraoperative application of steroids, iridium-coated Nucleus 24 Contour, and iridium-coated Nucleus 24 Contour with intraoperative application of steroids were compared. Results: Steroid application reduced impedances significantly throughout the observation period of up to 4 years after implantation. Iridium oxide coating had no effect. Differences between the groups were mainly found on the basal and middle parts of the cochlea, but not close to the tip of the array, also indicating that postoperative fibrous tissue growth is stronger in the basal region of the cochlea. Group mean values of the stimulation effect were not influenced by the different treatments. Nevertheless, only in both steroid-treated groups a correlation between the impedance before stimulation and the stimulation effect was found. Conclusion: Although the differences between control and steroid-treated groups decrease with time, single intraoperative intracochlear steroid deposition was proven to lower postoperative impedances during first 3 to 4 years after implantation probably because of reduction of fibrous tissue growth.

Impact of the insertion speed of cochlear implant electrodes on the insertion forces.

Hypothesis: Objective of the present experimental research study was to examine the hypothesis that cochlear implant insertion speed can significantly affect the insertion forces. Background: Cochlear implant electrode insertion forces can influence the insertion trauma and the preservation of residual hearing. The effect of the electrode insertion speed on the insertion forces still remains unknown. Methods: Force measurements were performed while inserting human electrodes in an artificial scala tympani model at different speeds. For these measurements, an Instron 5542 Force Measurement System with a 10 N load cell and Nucleus 24 Contour Advance electrodes were used. Additionally, the insertion speed was measured through videos of 116 human implantations; these videos were recorded in our theaters and involved different surgeons and electrode types. Results: Progressive increase in insertion speed from 10 to 200 mm/min resulted in significant, proportional increase in the average insertion forces from 0.09 to 0.185 N and in the maximum forces from 0.18 to 0.42 N, respectively. The average insertion speed used in the theaters during human cochlear implantations was 96.5 mm/min (range, 42-165.2 mm/min) and depended on the electrode type and the surgeon. Conclusion: High insertion speeds cause significant increase of the forces. Cochlear implant surgeons should use low and stable speeds during the insertion. Insertion speed close to the average value used in the theaters should be applied on experimental models, to approximate human implantation conditions.

Insertion site and sealing technique affect residual hearing and tissue formation after cochlear implantation

Tissue formation around the electrode array of a cochlear implant has been suggested to influence preservation of residual hearing as well as electrical hearing performance of implanted subjects. Further, inhomogeneity in the electrical properties of the scala tympani shape the electrical field and affect current spread. Intracochlear trauma due to electrode insertion and the insertion site itself are commonly seen as triggers for the tissue formation. The present study investigates whether the insertion site, round window membrane (RWM) vs. cochleostomy (CS), or the sealing material, no seal vs. muscle graft vs. carboxylate cement, have an influence on the amount of fibrous tissue and/or new bone formation after CI implantation in the guinea pig. Hearing thresholds were determined by auditory brainstem response (ABR) measurements prior to implantation and after 28 days. The amount of tissue formation was quantified by evaluation of microscopic images obtained by a grinding/polishing procedure to keep the CI in place during histological processing. An insertion via the round window membrane resulted after 28 days in less tissue formation in the no seal and muscle seal condition compared to the cochleostomy approach. Between these two sealing techniques there was no difference. Sealing the cochlea with carboxylate cement resulted always in a strong new bone formation and almost total loss of residual hearing. The amount of tissue formation and the hearing loss correlated at 1-8 kHz. Consequently, the use of carboxylate cement as a sealing material in cochlear implantation should be avoided even in animal studies, whereas sealing the insertion site with a muscle graft did not induce an additional tissue growth compared to omitting a seal. For hearing preservation the round window approach should be used.

Neurite outgrowth on cultured spiral ganglion neurons induced by erythropoietin

The morphological correlate of deafness is the loss of hair cells with subsequent degeneration of spiral ganglion neurons (SGN). Neurotrophic factors have a neuroprotective effect, and especially brain-derived neurotrophic factor (BDNF) has been demonstrated to protect SGN in vitro and after ototoxic trauma in vivo. Erythropoietin (EPO) attenuates hair cell loss in rat cochlea explants that were treated with gentamycin. Recently, it has also been shown that EPO reduces the apoptose rate in hippocampal neurons. Therefore, the aim of the study was to examine the effects of EPO on SGN in vitro. Spiral ganglion cells were isolated from neonatal rats and cultured for 48 h in serum-free medium supplemented with EPO and/or BDNF. Results showed that survival rates of SGN were not significantly improved when cultivated with EPO alone. Also, EPO did not further increase BDNF-induced survival of SGN. However, significant elongation of neurites was determined when SGN were cultivated with EPO alone. Even though a less than additive effect was observed, combined treatment with BDNF and EPO led to a significant elongation of neurites when compared to individual treatment with BDNF or EPO. It can be concluded that EPO induces neurite outgrowth rather than promoting survival. Thus, EPO presents as an interesting candidate to enhance and modulate the regenerative effect of BDNF on SGN.

Stable release of BDNF from the fibroblast cell line NIH3T3 grown on silicone elastomers enhances survival of spiral ganglion cells in vitro and in vivo.

The treatment of choice for profound sensorineural hearing loss (SNHL) is direct electrical stimulation of spiral ganglion cells (SGC) via a cochlear implant (CI). The number and excitability of SGC seem to be critical for the success that can be achieved via CI treatment. However, SNHL is associated with degeneration of SGC. Long-term drug delivery to the inner ear for improving SGC survival may be achieved by functionalisation of CI electrodes with cells providing growth factors. Therefore, the capacity of brain-derived neurotrophic factor (BDNF)-secreting NIH3T3 cells grown on cylindrically shaped silicone elastomers (SE) to exert local and sustained neuroprotective effects was assessed in vitro and in vivo. An in vitro model to investigate adhesion and cell growth of lentivirally modified NIH3T3 cells synthesising BDNF on SE was established. The bioactivity of BDNF was characterised by co-cultivation of SGC with cell-coated SE. In addition, cell-coated SE were implanted into deafened guinea pigs. The recombinant NIH3T3 cells proliferated on silicone surfaces during 14 days of cultivation and expressed significantly increasing BDNF levels. Enhanced survival rates and neurite outgrowth of SGC demonstrated the bioactivity of BDNF in vitro. Implantation of SE with adhering BDNF-secreting NIH3T3 cells into the cochleae of systemically deafened guinea pigs induced a significant increase in SGC survival in comparison to SE without cell coating. Our data demonstrate a novel approach of cell-based long-term drug delivery to support SGC survival in vitro and in vivo. This therapeutic strategy--once transferred to cells suitable for clinical application--may improve CI performance.

Development of a specially tailored local drug delivery system for the prevention of fibrosis after insertion of cochlear implants into the inner ear

A cochlear implant (CI)-associated local drug delivery system based on dexamethasone (DMS) was developed with the purpose to inhibit the growth of fibrotic tissue which influences the signal transmission from the CI to the neurons of the inner ear. For the realization of a targeted DMS delivery the following concepts were combined: modification of the silicone-based electrode carrier by incorporation of DMS and a DMS-containing polymeric coating chemically attached on the surface of the electrode carrier. It was demonstrated that the coated CI showed a high coating stability in a simulated implantation procedure. The in vitro drug release studies in a quasi-stationary model revealed a faster DMS release in the initial phase originating from the DMS-containing coatings and then a lower and sustained DMS release originating from the DMS-loaded silicone carrier. The performed in vitro biocompatibility study confirmed that the released DMS was non-toxic for cultured spiral ganglion cells.