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Hypothesis: Making a cochleostomy with a laser can affect the inner ear function., Background: Different types of lasers can be used to create a fenestration in the footplate of the stapes during stapedotomy. Because of variations in absorption spectra of the laser light in various tissues or fluids, each laser has its own characteristics and possible side effects., Materials and Methods: The basal turns of the cochleae of 20 guinea pigs were fenestrated using 4 types of lasers (thulium, KTP, CO2, diode; all groups n = 4). A control group (n = 4) was included to correct for the effects of the surgery alone. At 3 different time points, acoustically evoked compound action potentials (CAPs) were recorded at 5 frequencies and at different sound pressure levels. N1-P2 amplitudes were measured, and subsequently, thresholds were calculated. A repeated measures analysis of variance was used to investigate differences between groups., Results: There was a decrease in CAP amplitudes and an increase in CAP thresholds after cochleostomy with each laser. The increase in thresholds was significantly larger for higher frequencies. The thulium laser evoked the largest threshold shifts, the KTP laser the smallest with the CO2, and diode lasers in intermediate positions. Overall, there was an increase in latencies after treatment., Conclusion: Laser treatment on or near the cochlea can cause damage to the sensitivity of the cochlea for sound. The thulium laser seems to be the worst choice in this respect.

Hypothesis: Using an appropriate dose of an aminoglycoside antibiotic cotreated with a loop diuretic a guinea pig model of high-frequency loss can be obtained mimicking cochlear implant candidates with low-frequency residual hearing. We examined the stability of this model over time., Background: A well-established method to create an animal model for profound deafness is cotreatment with an aminoglycoside antibiotic and a loop diuretic. Recent data indicated that reduction of the aminoglycoside dose might yield selective high-frequency hearing loss. Such a model is relevant for studies related to hybrid cochlear implant devices, for example, with respect to preservation of residual hearing., Methods: Guinea pigs received an electrode for chronic recording of compound action potentials to tones to assess thresholds. They were treated with a coadministration of kanamycin (200 mg/kg) and furosemide (100 mg/kg), after which, the animals were sacrificed for histologic analysis at 2, 4, or 7 weeks., Results: After 2 to 7 weeks threshold shifts were greater than 50 dB for 8 to 16 kHz in 15 of 17 animals, whereas threshold shifts at 2 kHz or lower were less than 50 dB in 13 animals. Major threshold shifts occurred the first 2 to 4 days; subsequently, some spontaneous recovery occurred and, after 2-3 weeks thresholds, remained stable. Inner hair cell loss still progressed between 2 and 4 weeks in the most basal cochlear region; thereafter, hair cell loss was stable., Conclusion: An appropriate animal model for selective severe high-frequency hearing loss was obtained, which is stable at 4 weeks after ototoxic treatment.

Hypothesis: How to induce most efficiently severe sensorineural hearing loss in mice using a single coadministration of an aminoglycoside antibiotic and a loop diuretic?, Background: The coadministration of aminoglycosides and a loop diuretic has been widely used to induce hair cell and spiral ganglion cell loss in guinea pigs. However, the development of new treatment strategies against sensorineural hearing loss, such as tissue engineering techniques, requires the use of mouse models. Previous attempts to induce hearing loss in mice have rendered inconsistent results because of resistance to aminoglycoside-induced ototoxicity. Especially inner hair cells seem to be resistant to aminoglycoside-induced ototoxicity., Methods: In the present study, we aim to optimize hearing loss in mice, using a single high-dose kanamycin (700 and 1,000 mg/kg) injection followed by a furosemide (100 mg/kg) administration. Although previous studies used intraperitoneal furosemide injections 30 minutes after kanamycin administration, we used intravenous furosemide injections administered within 5 minutes after kanamycin treatment., Results: Auditory brain stem responses illustrated severe threshold shifts, and histologic analysis showed marked outer hair cell destruction as well as spiral ganglion cell loss. The present protocol results in more severe inner hair cell loss when compared with the results of previous researches., Conclusion: We conclude that severe sensorineural hearing loss can be induced in mice. Moreover, we found that this mouse model can be augmented via the use of rapid intravenous furosemide administrations to maximize inner hair cell loss.

Hypothesis: Interactions between cochlear responses to combined electrical and acoustic stimulation (EAS) depend on electrically evoked hair cell activity (i.e., electrophonics)., Background: Although relevant for EAS strategies in cochlear implant users with residual low-frequency hearing, cochlear responses to EAS are not well characterized. Previously, we have shown that acoustically evoked compound action potentials (CAPs) can be suppressed by electrical stimulation. In the present study, we characterized the role of electrophonics in CAP suppression in guinea pigs, under conditions representative of clinically applied EAS., Methods: Electrophonics depend on the frequency spectrum of the electric pulse train, which is mainly determined by pulse width and, to a lesser extent, by pulse rate. We measured suppression of tone-evoked CAPs by electric pulse trains, while varying the pulse width (80 - 400 μs, n = 5) and the pulse rate (500 - 4000 pps, n = 5). The role of outer hair cells (OHCs) in electrophonics was tested in animals with varying degrees of OHC loss (n = 24)., Results: Suppression of acoustically evoked CAPs varied with pulse width, indicating that electrophonics were involved. Short pulse widths resulted in minimal CAP suppression at low acoustic frequencies. Pulse rate did not significantly affect CAP suppression. OHC loss had no significant effect on electrophonic activity., Conclusion: Electrophonic activity was present in cochleae with extensive basal hair cell loss, indicating that electrophonics can occur in EAS users. Our results show that short pulse widths are optimal for use in EAS stimulation strategies, on the assumption that minimal suppression is best.

Hypothesis: Limiting spatial overlap between electrical stimulation (ES) and acoustical stimulation (AS) in the cochlea reduces the effects of AS on electrically evoked auditory nerve activity., Background: Some hybrid cochlear implant systems have a regular array, whereas others have short arrays that spatially segregate ES from AS. AS settings in hybrid implants may also affect electroacoustic interaction., Methods: ES (900 μA) was delivered in the high-frequency part of the cochlea, and the electrically evoked compound action potential (eCAP) was recorded to assess auditory nerve activity. Maximal spatial overlap of ES and AS was tested by using normal-hearing animals (NH, n = 6), whereas minimal overlap was modeled by using animals with high-frequency hearing loss (HFHL, n = 6). AS consisted of broadband (BB) or low-frequency (LF) noise (0-100 dB SPL). Effects of AS on eCAP amplitude were statistically tested using 1-sample t tests (α = 0.05)., Results: BB noise at 60 dB SPL significantly suppressed eCAP amplitude in NH animals but not in HFHL animals up to a 30 dB higher level. Suppression with LF noise at 60 dB SPL was not significant in either the NH or the HFHL group, but at 90 dB SPL, suppression was significant in both groups., Conclusion: Minimizing spatial overlap between ES and AS reduces eCAP suppression when moderate sound levels are applied. Overlap can be reduced by applying ES in an acoustically insensitive part of the cochlea or by limiting the acoustic spectrum to low frequencies when ES is applied in acoustically sensitive areas.

Background: Currently, Ménière's disease is predominantly diagnosed through clinical criteria. Additional standard vestibular testing, such as nystagmography, can show variable responses. In the last decade, the cervical vestibular evoked myogenic potential (VEMP) has shown to be of additive value in diagnosing Ménière's disease. In this study, the results of the ocular VEMP (oVEMP) in response to air-conducted sound will be discussed., Objectives: To evaluate possible changes of the oVEMP in a large group (n = 37) of patients with Ménière's disease., Material and Methods: In 55 subjects without Ménière's disease and 37 patients with Ménière's disease, oVEMPs in response to air-conducted sound stimulation (tone-burst, 500 Hz; maximum stimulus level, 120 dB sound pressure level) were studied. Recording was performed in upgaze with surface electrodes underneath both eyes. The burden of the test was scored by all subjects on a visual analogue scale., Results: In patients with Ménière's disease the response rates are lower, the oVEMP amplitudes are smaller, and thresholds are higher than in subjects without Ménière's disease. This effect is observed in both ears of patients with Ménière's disease. The affected ear is more altered than the clinically unaffected ear., Conclusion: The air-conducted oVEMP can be a relevant addition to the current diagnostic workup of patients with possible Ménière's disease. A lower response rate, smaller amplitude, and higher threshold of the oVEMP indicate the pathologic disease in this population.