Protecting against electrode insertion trauma using dexamethasone.

OBJECTIVE: To compare the benefits of a dexamethasone-eluting array for hearing preservation and cochlear histopathology in low trauma (soft-surgery) and high trauma models of cochlear implant surgery. METHODS: Adult guinea pigs were implanted with an intra-cochlear array using two different surgical procedures: either a soft-surgery approach or following generation of electrode insertion trauma (high trauma). Two methods of dexamethasone delivery were evaluated: elution from an electrode array alone, and elution from a cochlear implant electrode array in combination with a pre-operative systemic injection. All electrode arrays were implanted for a period of 4 weeks. Outcome measures at 4 weeks post-implantation included auditory brainstem response (ABR) thresholds, histological analysis of spiral ganglion neuron density, fibrotic tissue, new bone growth, and cochlear damage. RESULTS: Animals exposed to high surgical trauma showed greater hearing loss than those in the low trauma model, irrespective of the presence of dexamethasone. Whilst the area of intra-cochlear fibrotic tissue growth post-implantation was also independent of dexamethasone administration, new bone growth was significantly reduced in its presence. Our high trauma model effectively obliterated the organ of Corti and significantly reduced spiral ganglion neuron densities in the lower basal turn. This trauma-induced reduction in spiral ganglion neuron survival decreased with the inclusion of a dexamethasone-eluting array. A pre-operative systemic injection of dexamethasone did not significantly improve any outcome measures beyond those provided with a dexamethasone-eluting array alone. CONCLUSION: Dexamethasone-eluting intra-cochlear arrays may inhibit osteoneogenesis, and reduce spiral ganglion neuron loss following traumatic cochlear implantation.

Electrode Impedance Fluctuations as a Biomarker for Inner Ear Pathology After Cochlear Implantation.

OBJECTIVES/HYPOTHESIS: Cochlear implant surgery now aims to preserve residual low frequency hearing. The current research explores whether fluctuations in the electrical impedance of cochlear implant electrodes may act as a biomarker for pathological changes that lead to the delayed loss of residual hearing. STUDY DESIGN: Secondary analysis of a double-blinded randomized trial, where methylprednisolone was administered intravenously before cochlear implantation with a view to preserving residual hearing. METHODS: Seventy-four patients with residual hearing after cochlear implant surgery were investigated for an impedance "spike," defined as a median rise of ≥4 kΩ across all electrodes from the baseline measurements. Spikes were related to objective and subjective hearing loss, dizziness, and tinnitus. RESULTS: An impedance spike occurred in 14% (10/74) of enrolled patients. Three months after surgery, five patients exhibited spikes and three of these patients had a total loss of their residual hearing. 4.3% of the 69 patients without spikes lost residual hearing. At 1 year, 9 of 10 patients who exhibited spikes had lost all their residual hearing. 8.1% of the 37 patients who did not experience a spike lost their residual hearing. Seventy percent of patients exhibiting a spike also experienced vertigo. The administration of steroids at the time of surgery did not influence the occurrence of spikes. CONCLUSION: Our results suggest that there is a relationship between a spike and the loss of residual hearing. It seems that rises in impedance can reflect pathology within the inner ear and predict the future loss of residual hearing.

Long-term electrode impedance changes and failure prevalence in cochlear implants.

OBJECTIVE: This study assessed the prevalence of electrode failures and electrode impedance measures in Nucleus cochlear implants around initial activation (an average of 16 days after surgery) and after 8 to 12 years of device use. DESIGN: Retrospective data from the Melbourne Cochlear Implant Clinic was collated and analysed. STUDY SAMPLE: Included in this study were 232 adults, all of whom were implanted at the clinic between March 1998 and August 2005. RESULTS: Overall 0.5% of electrodes failed over the entire test period, with 5.6% of devices showing one or more electrode failure. The majority of these failures were recorded by initial activation. The numbers of electrode failures have decreased over time with array type, such that no failures were recorded with the currently available Contour Advance array. Array type was shown to affect electrode impedance at both time points, with the Contour and Contour Advance arrays having significantly higher absolute values than the Banded array. However, the Banded array had significantly higher area-normalized impedances at initial and final measures than the Contour and Contour Advance array. CONCLUSIONS: A relatively low incidence of electrode failures were recorded for the Nucleus devices of these recipients. Electrode impedance dropped for all array types after 8 to 12 years of device use.

Meningitis and a safe dexamethasone-eluting intracochlear electrode array.

OBJECTIVES: To evaluate the potential risk of pneumococcal meningitis associated with the use of a dexamethasone-eluting intracochlear electrode array as compared with a control array. METHODS: In two phases, adult Hooded-Wistar rats were implanted via the middle ear with an intracochlear array and were inoculated with Streptococcus pneumoniae 5 days post-surgery. Phase I created a dosing curve by implanting five groups (n = 6) with a control array, then inoculating 5 days later with different numbers of S. pneumoniae: 0 CFU, 10(3) CFU, 10(4) CFU, 10(4) CFU repeated, or 10(5) CFU (colony forming units). A target infection rate of 20% was aimed for and 10(4) CFU was the closest to this target with 33% infection rate. In phase II, we implanted two groups (n = 10), one with a dexamethasone-eluting array, the other a control array, and both groups were inoculated with 10(4) CFU of S. pneumoniae 5 days post-surgery. RESULTS: The dexamethasone-eluting array group had a 40% infection rate; the control array group had a 60% infection rate. This difference was not statistically significant with a P value of ≥0.5. CONCLUSION: The use of a dexamethasone-eluting intracochlear electrode array did not increase the risk of meningitis in rats when inoculated with S. pneumoniae via the middle ear 5 days following implantation.

Electropermeabilization of adherent cells with cochlear implant electrical stimulation in vitro.

Cochlear implant stimulation creates a reduction in electrode impedance that returns to pre-stimulation levels following cessation of stimulation and is presumed to be associated with the fibrous tissue covering over the electrode array. This study assessed the possibility that transitory impedance reduction originates from a change in the membrane permeability of cells on the electrode (electropermeabilization). These changes can be recorded using the dye propidium iodide, which fluoresces upon entry into the leaky cell. The in vitro model used showed impedance reduction and dye uptake into adherent cells overlying planar gold electrodes stimulated with as little as 5 min of clinically relevant cochlear implant stimulation. The delayed additions of propidium iodide showed a similar dye uptake to those groups with concurrent dye addition, suggesting the electropermeabilization was not reversible. Further understanding of the mechanisms behind these impedance and cell permeability changes with cochlear implant electrical stimulation may provide opportunities for creating long-lasting reductions in electrode impedance.

Development of a safe dexamethasone-eluting electrode array for cochlear implantation.

OBJECTIVES: Cochlear implantation can result in trauma leading to increased tissue response and loss of residual hearing. A single intratympanic application of the corticosteroid dexamethasone is sometimes used clinically during surgery to combat the potential effect of trauma on residual hearing. This project looked at the safety and efficacy of dexamethasone eluted from an intracochlear array in vivo. METHODS: Three trials were conducted using normal hearing adult guinea pigs implanted with successive iterations of dexamethasone-eluting (DX1, DX2, and DX3) or non-eluting (control) intracochlear electrode arrays. The experimental period for each animal was 90 days during which hearing tests were performed at multiple time points. RESULTS: There was no significant difference between matched control array and dexamethasone array groups in terms of spiral ganglion neuron density, organ of Corti condition, or fibrosis and ossification. A cochleostomy seal was present in all implanted cochleae. There were no differences in the degree of hearing threshold shifts between DX1 and DX3 and their respective control arrays. Cochleae implanted with DX2 arrays showed less hearing loss and marginally better spiral ganglion neuron survival than their control array counterparts. Post-explant inspection of the DX2 and DX3 arrays revealed a difference in pore density following dexamethasone elution. CONCLUSION: The dexamethasone doses used were safe in the guinea pig cochlea. Dexamethasone did not inhibit formation of a cochleostomy seal. The level of hearing protection afforded by dexamethasone eluting from an intracochlear array may depend upon the degree of elution and level of trauma inflicted.

Micro-focus fluoroscopy - a great tool for electrode development.

The aim of this study was to utilise micro-focus X-ray fluoroscopy for viewing electrode movement in the cochlea. Various prototypes of newly designed cochlear implant electrodes were evaluated during insertion studies on human cadaver temporal bones. The magnified fluoroscopic images were observed in real-time and recorded for retrospective studies. In 30 insertions of hearing preservation (Hybrid-L) arrays, fluoroscopy provided crucial information on the tip design, length of array and stiffening stylet. In 44 insertions of Contour Advance enhanced (CAe) arrays, the length, curvature, depth of insertion and degree of stiffness were assessed. CAe arrays were successfully inserted to the designated depth and positioned close to the modiolus. High quality micro-focus fluoroscopic images of electrode movement in the cochlea greatly assisted in the validation of newly designed intra-cochlear electrode arrays.

The effect of polypyrrole with incorporated neurotrophin-3 on the promotion of neurite outgrowth from auditory neurons.

This research aims to improve the nerve-electrode interface of the cochlear implant using polymer technology to encourage neuron survival, elongation and adhesion to the electrodes. Polypyrrole (Ppy) doped with p-toluene sulphonate (pTS) is an electroactive polymer into which neurotrophin-3 (NT3) can be incorporated. Ppy/pTS+/-NT3 was synthesised over gold electrodes and used as a surface for auditory neuron explant culture. Neurite outgrowth from explants grown on Ppy/pTS was equivalent to tissue culture plastic but improved with the incorporation of NT3 (Ppy/pTS/NT3). Electrical stimulation of Ppy/pTS/NT3 with a biphasic current pulse, as used in cochlear implants, significantly improved neurite outgrowth from explants. Using (125)I-NT3, it was shown that low levels of NT3 passively diffused from Ppy/pTS/NT3 during normal incubation and that electrical stimulation enhanced the release of biologically active NT3 in quantities adequate for neuron survival. Furthermore, Ppy/pTS/NT3 and its constituents were not toxic to auditory neurons and the Ppy/pTS/NT3 coating on gold electrodes did not alter impedance. If applied to the cochlear implant, Ppy/pTS/NT3 will provide a biocompatible, low-impedance substrate for storage and release of NT3 to help protect auditory neurons from degradation after sensorineural hearing loss and encourage neurite outgrowth towards the electrodes.

An in vitro model for investigating impedance changes with cell growth and electrical stimulation: implications for cochlear implants.

The impedance of stimulating electrodes used in cochlear implants and other neural prostheses often increases post-implantation, and is thought to be due to fibrous tissue encapsulation of the electrode array. Increased impedance results in higher power requirements to stimulate target neurons at set charge densities. We developed an in vitro model to investigate the electrode-tissue interface in a highly controlled environment. This model was tested using three cell types, with and without charge-balanced biphasic electrical stimulation. Under standard tissue culture conditions, a monolayer of cells was grown over the electrode surface. Electrode impedance increased in proportion to the extent of cell coverage of the electrode. Cell type was a significant factor in the amount of impedance increase, with kidney epithelial cells (MDCK) creating the greatest impedance, followed by dissociated rat skin fibroblasts and then macrophages (J774). The application of electrical stimulation to cell-covered electrodes caused impedance fluctuations similar to that seen in vivo, with a lowering of impedance immediately following stimulation, and a recovery to pre-stimulation levels during inactive periods. Examination of these electrodes suggests that the stimulation-induced impedance changes were due to the amount of cell cover over the electrodes. This in vitro technique accurately models the changes in impedance observed with neural prostheses in vivo, and shows the close relationship between impedance and tissue coverage adjacent to the electrode surface. We believe that this in vitro approach holds great promise to further our knowledge of the mechanisms contributing to electrode impedance.