Gentiana I. Wenzel

Cochlear Implantation in Unilateral Deaf Subjects Associated With Ipsilateral Tinnitus

Objective: In subjects who are deaf and who also have tinnitus in the affected ear, tinnitus treatments based on acoustic input are impossible. On the other hand, tinnitus suppression using electric stimulation has been reported to be successful. Therefore, a study was initiated to investigate the potential of cochlear implantation (CI) in unilateral deaf subjects regarding tinnitus suppression, device acceptance, and restoration of spatial hearing. Method: Five subjects with severe to profound unilateral deafness having also ipsilateral tinnitus were enrolled. In monthly visits, the speech processor program was optimized, and the hearing performance as well as tinnitus were monitored. In addition, it was investigated whether the CI improves hearing in adverse listening situations when combined with the normal hearing side. Results: In 3 participants, the tinnitus was significantly suppressed while wearing the device. In the other 2 participants, the tinnitus could be reduced in certain situations. Speech perception tests revealed a significant benefit with the CI in combination with the normal-hearing side for 3 participants. All participants accepted the device in a clinical setting; adaptation of the frequency allocation was not required. Conclusion: Improvements were found regarding the hearing and the tinnitus. Not all participants benefit from the CI to the same degree and in the same situations. The results indicate that cochlear implantation in subjects with unilateral severe to profound hearing loss and ipsilateral tinnitus may be beneficial on a case-to-case basis. Further work needs to be performed to define the appropriate indication criteria.

Green laser light activates the inner ear

The hearing performance with conventional hearing aids and cochlear implants is dramatically reduced in noisy environments and for sounds more complex than speech (e. g. music), partially due to the lack of localized sensorineural activation across different frequency regions with these devices. Laser light can be focused in a controlled manner and may provide more localized activation of the inner ear, the cochlea. We sought to assess whether visible light with parameters that could induce an optoacoustic effect (532 nm, 10-ns pulses) would activate the cochlea. Auditory brainstem responses (ABRs) were recorded preoperatively in anesthetized guinea pigs to confirm normal hearing. After opening the bulla, a 50-microm core-diameter optical fiber was positioned in the round window niche and directed toward the basilar membrane. Optically induced ABRs (OABRs), similar in shape to those of acoustic stimulation, were elicited with single pulses. The OABR peaks increased with energy level (0.6 to 23 microJ/pulse) and remained consistent even after 30 minutes of continuous stimulation at 13 microJ, indicating minimal or no stimulation-induced damage within the cochlea. Our findings demonstrate that visible light can effectively and reliably activate the cochlea without any apparent damage. Further studies are in progress to investigate the frequency-specific nature and mechanism of green light cochlear activation.

Optoacoustic induced vibrations within the inner ear

An acoustic transient can be generated inside an absorbing tissue as a result of laser-tissue interaction after pulsed laser irradiation. Herein we report a novel application of this physical process, the optoacoustic wave generation in the inner ear and subsequently the induction of basilar membrane vibrations. These laser induced vibrations show a direct correlation to the laser energy and an indirect correlation to the distance from the irradiation focus. Through these characteristics they may be used, in a new generation of cochlear implants, to improve the frequency specific cochlear activation and consequently improve speech perception in hearing impaired patients with residual hearing.

Contact endoscopy for the evaluation of the pharyngeal and laryngeal mucosa

Contact endoscopy is a noninvasive tool that allows in vivo and in situ examination of superficial mucosa. Its use for early diagnosis of cancerous lesions of the oropharynx and larynx has not been evaluated. The aim of the study was to validate contact endoscopy for the examination of pharyngeal and laryngeal mucosa.

Helper-dependent adenovirus-mediated gene transfer into the adult mouse cochlea.

Background: Gene therapy may provide a way to restore cochlear function to deaf patients. The most successful techniques for cochlear gene therapy have been injection of early-generation adenoviral vectors into scala media in guinea pigs. However, it is important to be able to perform gene therapy research in mice because there is wide availability of transgenic strains with hereditary hearing loss. Purpose: We demonstrate our technique for delivery of a third-generation adenoviral vector, helper-dependent adenovirus (HDAd), to the adult mouse cochlea. Methods: Mice were injected with an HDAd that contained a reporter gene for either β-galactosidase or green fluorescent protein into scala media. After 4 days, the cochleae were harvested for analyses. Auditory brainstem response monitoring of cochlear function was performed before making a cochleostomy, after making a cochleostomy, and before killing the animal. Results: β-Galactosidase was identified in the spiral ligament, the organ of Corti, and spiral ganglion cells by light microscopy. Green fluorescent protein epifluorescence was assessed in whole-mount organ of Corti preparations using confocal microscopy. This demonstrated transduction of inner hair cells, outer hair cells, and supporting cells. Paraffin-embedded cross sections similarly revealed gene transduction within the organ of Corti. Threshold shifts of 39.8 ± 5.4 and 37.7 ± 5.5 dB were observed in mice injected with HDAd or control buffer, respectively. Conclusion: The technique of scala media HDAd injection reliably infects the adult mouse cochlea, including cells within the organ of Corti, although the procedure itself adversely affects hearing.

Optical cochlear implant: evaluation of insertion forces of optical fibres in a cochlear model and of traumata in human temporal bones.

Abstract Optical stimulation for hearing restoration is developing as an alternative therapy to electrical stimulation. For a more frequency-specific activation of the auditory system, light-guiding fibres need to be inserted into the coiled cochlea. To enable insertion with minimal trauma, glass fibres embedded in silicone were used as models. Thus, glass fibres of varying core/cladding diameter with and without silicon coating (single as well as in bundles) were inserted into a human scala tympani (ST) model. Insertion cochlear model force measurements were performed, and the thinner glass fibres that showed low insertion forces in the model were inserted into cadaveric human temporal bones. Silicone-coated glass fibres with different core/cladding diameters and bundle sizes could be inserted up to a maximum depth of 20 mm. Fibres with a core/cladding diameter of 50/55 μm break during insertion deeper than 7–15 mm into the ST model, whereas thinner fibres (20/25 μm) could be inserted in the model without breakage and in human temporal bones without causing trauma to the inner ear structures. The insertion forces of silicone-coated glass fibres are comparable to those measured with conventional cochlear implant (CI) electrodes. As demonstrated in human temporal bones, a minimal traumatic implantation of an optical CI may be considered feasible.

Laser-induced collagen remodeling and deposition within the basilar membrane of the mouse cochlea

The cochlea is the mammalian organ of hearing. Its predominant vibratory element, the basilar membrane, is tonotopically tuned, based on the spatial variation of its mass and stiffness. The constituent collagen fibers of the basilar membrane affect its stiffness. Laser irradiation can induce collagen remodeling and deposition in various tissues. We tested whether similar effects could be induced within the basilar membrane. Trypan blue was perfused into the scala tympani of anesthetized mice to stain the basilar membrane. We then irradiated the cochleas with a 694-nm pulsed ruby laser at 15 or 180 Jcm(2). The mice were sacrificed 14 to 16 days later and collagen organization was studied. Polarization microscopy revealed that laser irradiation increased the birefringence within the basilar membrane in a dose-dependent manner. Electron microscopy demonstrated an increase in the density of collagen fibers and the deposition of new fibrils between collagen fibers after laser irradiation. As an assessment of hearing, auditory brainstem response (ABR) thresholds were found to increase moderately after 15 Jcm(2) and substantially after 180 Jcm(2). Our results demonstrate that collagen remodeling and new collagen deposition occurs within the basilar membrane after laser irradiation in a similar fashion to that found in other tissues.

Artemin improves survival of spiral ganglion neurons in vivo and in vitro.

Artemin and its receptors are upregulated in the auditory nerve of deafened rats as a possible intrinsic protective mechanism against ototoxicity-related apoptosis. Consequently, we examined the effect of artemin on spiral ganglion neurons in vitro and in vivo. Spiral ganglion neurons were isolated from neonatal rats and cultured in serum-free medium supplemented with artemin and/or brain-derived neurotrophic factor (BDNF). In vitro, the survival rate of spiral ganglion neurons cultivated with artemin or BDNF was significantly improved compared with negative controls. In addition, artemin was delivered to the inner ear of deafened guinea pigs for 28 days. In-vivo artemin was as effective as BDNF in spiral ganglion neuron protection. Therefore, artemin promotes the survival of spiral ganglion neurons in vitro and in vivo.

Ossiculoplasty in missing malleus and stapes patients: experimental and preliminary clinical results with a new malleus replacement prosthesis with the otology-neurotology database.

Objective To present the preliminary results of new malleus replacement prosthesis combined with a total ossicular prosthesis in middle ear reconstruction in patients missing the malleus and stapes. Study Design Prospective experimental and nonrandomized clinical study. Setting Tertiary referral center. Methods An original titanium malleus replacement prosthesis (MRP) was designed to be inserted into the external auditory canal and to replace a missing malleus for various middle ear pathologies. The MRP was tested experimentally and clinically. The vibratory properties of the new prosthesis were measured using laser Doppler vibrometry. Ninety patients with missing malleus and stapes, undergoing 92 ossicular reconstructions were enrolled in this study from September 1994 to March 2012. Comparative analyses were made between a group of 34 cases of ossicular reconstructions with total prosthesis (TORP) positioned from the tympanic membrane to the stapes footplate (TM-to-footplate assembly) and a group of 58 cases of ossicular reconstructions with TORP positioned from a newly designed malleus replacement prosthesis (MRP) to the stapes footplate (MRP-to-footplate assembly). Preoperative and postoperative audiometric evaluation using conventional audiometry, that is, air-bone gap (ABG), bone-conduction thresholds (BC), and air-conduction thresholds (AC) were assessed. Results Experimentally, the vibratory properties of the MRP are promising and remain very good even when the MRP is cemented into the bony canal wall mimicking its complete osseous-integration, if this were to occur. This finding supports the short-term clinical results as in the TM-to-footplate group; the 3-month postoperative mean ABG was 23.3 dB compared with 12.5 dB in the MRP-to-footplate group (difference, 10.8; 95% confidence interval, 4.0–17.6); 37.0% of patients from the TM-to-footplate group had a postoperative ABG of 10 dB or less, and 48.1% of patients had a postoperative ABG of 20 dB or less, as compared with 58.1% and 79.1%, respectively, in the MRP-to-footplate group. The average gain in AC was 11.0 dB in the TM-to-footplate group as compared with 21.3 dB in the MRP-to-footplate group (difference, –10.3; 95% confidence interval, –18.2 to –2.4). Conclusion The results of this study indicate that superior postoperative hearing thresholds could be achieved using a MRP-to-footplate assembly, compared with a TM-to-footplate assembly in patients with an absent malleus undergoing ossiculoplasty. The postoperative AC thresholds, after 3 months and 1 year, are significantly lower in patients treated with the MRP-to-footplate assembly.

Stimulation of the cochlea using green laser light

The success of conventional hearing aids and electrical cochlear implants have generally been limited to hearing in quiet situations, in part due to a lack of localized (i.e., frequency specificity) sensorineural activation and subsequent impaired speech discrimination in noise. Laser light is a source of energy that can be focused in a controlled manner and may provide more localized activation of the inner ear, the cochlea. Compound action potentials have been elicited using 2.12 µm laser pulses through activation of auditory nerve fibers (Izzo et al. 2006). Laser stimulation (813 nm) of the cochlea has shown to induce basilar membrane motion and cochlear microphonic potentials (Fridberger et al. 2006). We sought to assess if visible light (green, 532 nm, 10 ns pulses) could be used to consistently activate the cochlea. The laser parameters were selected based on our initial attempt to induce an optoacoustic effect as the energy transfer mechanism to the cochlea. Click evoked auditory brainstem responses (AABRs) were recorded preoperatively in ketamine-anesthetized guinea pigs to confirm normal hearing. The bulla and then the cochlea were exposed. Optically evoked ABRs (OABR) were recorded in response to laser stimulation with a 50 µm optical fiber (532 nm, 10 ns pulses, 500 repetitions, 10 pulses/s; Nd:YAG laser) at the round window (RW) directed towards the basilar membrane (BM). OABRs similar in morphology to acoustically evoked ABRs, except for shorter latencies, were obtained for stimulation through the RW with energy levels between 1.7-30 µJ/pulse. The OABRs increased with increasing energy level reaching a saturation level around 13-15 µJ/pulse. Furthermore the responses remained consistent across stimulation over time, including stimulation at 13 µJ/pulse for over 30 minutes, indicating minimal or no damage within the cochlea with this type of laser stimulation. Overall we have demonstrated that laser light stimulation with 532 nm has potential for a new type of auditory prosthesis that can activate the cochlea without any apparent functional damage. Further studies are needed to determine the optimal laser parameters and fiber placement locations for localized and tonotopic activation.