Otolaryngology - Theses
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ItemLocal and systemic steroids in hearing preservation after cochlear implant surgery: are they equivalent?( 2019)Since the conception of the cochlear implant, the criteria for evaluating potential candidates has greatly expanded. We have seen a move to implanting a greater range of ages, including young children, implanting simultaneous bilateral ears, implantation in single sided deafness, and implanting those with a significant level of residual low-frequency hearing. The later permits a combination of electric stimulation from the implant, and natural acoustic stimulation, termed “electroacoustic stimulation”, that greatly enhances an individual’s speech recognition and music appreciation when compared to implant stimulation alone. Unfortunately, implantation often results in either early or delayed loss of residual hearing in the post-operative period. This is speculated to be the result of implantation trauma and delayed inflammatory events. In order for cochlear implantation to progress further, we now find ourselves with the predicament of how to best preserve this hearing. Despite a large body of research into hearing preservation strategies, we are still faced with unacceptable rates of hearing preservation. Corticosteroids are widely used in the peri-operative setting in an attempt to preserve hearing. It is widely believed that that they exert their effects by modulating the inflammatory reaction to an implant. Currently, little is known about the precise mechanism by which corticosteroids preserve hearing after cochlear implantation, or about the optimal administration regimes. The investigations in this thesis aim to explore the mechanism of action of corticosteroids in the context of hearing preservation after cochlear implantation, as well as compare the various routes of administration. Specifically, these investigations will compare local and systemically administered glucocorticoids, pharmacokinetics and pharmacodynamics within the inner ear, and provide a rationale for their administration regimes. Additionally, investigations in this thesis will explore the role of the mineralocorticoid receptor in the pathologic events following cochlear implantation.
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ItemTrauma and residual hearing loss after cochlear implantation surgery( 2019)For the last 30 years, cochlear implantation (CI) surgery has been successfully used for the treatment of severe to profound deafness. With improvements in cochlear implant technology, the surgical criteria have expanded to include patients with residual low frequency hearing. These patients can benefit from simultaneous use of the implant and a hearing aid in the same ear, termed electro-acoustic stimulation (EAS). EAS has been shown to be particularly beneficial for perceptual tasks relying on pitch resolution, such as music appreciation and speech perception in background noise (Gantz et al., 2005, Santa Maria et al., 2013). Unfortunately, residual hearing loss, termed post-implantation hearing loss, occurs in half of all patients, which degrades many of the benefits of EAS (Carlson et al., 2011). Post-implantation hearing loss may arise from direct surgical trauma and indirect damage to the cochlea (Eshraghi and Van de Water, 2006). The causes of direct trauma include surgical access to the cochlea and electrode insertion trauma. This results in several types of tissue injury, which may cause further hearing loss through a biological response, also termed indirect damage. However, the precise contributions of direct and indirect damage to post-implantation hearing loss remain indeterminate, in part, because of the lack of a standardised animal implantation model. Animal experimentations have been partly hampered by the difficult access to the mammalian inner ear and the absence of a consistent implantation technique (Rowe et al., 2016, Smeds et al., 2015, James et al., 2008) that has led to marked differences in the level of trauma and hearing loss (O'Leary et al., 2013, Farhadi et al., 2013, Honeder et al., 2015). The principal aim of this thesis was to examine the different types of cochlear trauma, how they relate to hearing loss and how hearing loss can be prevented. The issues that have been addressed here include cochlear anatomy and imaging techniques, pathology, pharmacology, electrophysiology and force recordings. This thesis begins by establishing a reproducible animal model of cochlear implantation surgery, followed by systematically examination the relevant contributors to surgical trauma and post-implantation hearing loss. From these findings, pharmacological therapy targeting the indirect damage and recording techniques to reduce post-implantation hearing loss have been investigated. An anatomical study of the guinea pig cochlea was initially performed using novel imaging and processing techniques. This study quantitatively described the soft and bony tissue relationships in the complex hook region of the unoperated guinea pig cochlea. A reproducible technique for implanting in an animal was established in this study for the remaining in vivo studies, including the use of a cochleostomy in an anteroinferior plane (highest predictability and smallest risk of trauma) and closer to the round window (lowest force profile). The first in vivo experiment of this thesis investigated the relative influence of implant insertion depth on trauma and hearing loss. This study also explored the use of glucocorticosteroids (‘steroids’) to preserve hearing and target the biological response to the implant. Key findings were that implants deeply inserted or in the presence of an osseous spiral lamina fracture caused the greatest low-frequency hearing loss. Steroids reduced the biological response in the most apical regions but had no effect on hearing thresholds. A second in vivo experiment was performed to further investigate the efficacy of steroids and to explore if trauma and hearing loss could be predicted at the time of surgery through force or electrocochleography recordings. Preserving the compound action potential of the electrocochleography recording was found to be predictive of an atraumatic insertion and reduced post-implantation hearing loss. Conversely, force was correlated with trauma but not hearing loss. Pre-operative steroids were effective in reversing the loss of hearing amplitudes evoked by lower frequency tones during implantation with hard electrodes. The results presented in this thesis will help inform the cochlear implant community of potential techniques to improve hearing preservation surgery. Specifically, these results provide a validated experimental model of hearing preservation surgery. These results also suggest a role for steroids in reducing tissue response and synaptopathy, and for electrocochleography as an intraoperative recording paradigm to reduce trauma and improve post-implantation hearing loss.
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ItemLocal delivery of Dexamethasone for the preservation of residual hearing in an animal cochlear implant model( 2015)This thesis uses an experimental model of cochlear implantation to examine the hearing protection afforded by the application of dexamethasone to the round window prior to surgery.
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ItemSystemic steroid protects residual hearing in a guinea pig model of cochlear implantation( 2011)Background: The protection of residual hearing is an important goal of cochlear implant surgery. Local application of steroids to the round window membrane (RWM) of the guinea pig prior to cochleostomy has been shown to protect hearing, but requires a period of pre-treatment for at least one hour. To determine whether this waiting period can be avoided, the efficacy of administering systemic steroids prior to cochlear implantation is investigated. Methods: Seventeen normal hearing guinea pigs were randomly assigned to receive a single preoperative intravenous injection of: 1) normal saline, 2) dexamethasone 0.2 mg/kg or 3) dexamethasone 2 mg/kg, 60 minutes before cochlear implantation. Implantation was completed with a silastic/platinum dummy electrode. Prior to surgery pure tone auditory brainstem response (ABR) thresholds were estimated from both ears separately in response to tone-pips from 2-32 kHz. This was again completed at 1 and 4 weeks postoperatively. The primary outcome measure was threshold shift at 1 and 4 weeks. Histology was examined for evidence of insertion trauma and foreign body reaction. Results: Preoperative injection of 2 mg/kg dexamethasone prevented an elevation in ABR thresholds at all frequencies compared with the control group (8 - 32 kHz) at 1 and 4 weeks post implantation. This protection was not seen with a lower dose (0.2mg/kg) of dexamethasone. There was a foreign body reaction observed in control and low-dose treated animals, however this was suppressed in all but one of the high-dose dexamethasone-treated animals. Conclusions: Intravenous high dose dexamethasone protects hearing during cochlear implantation and prevents the development of an inflammatory histological response. The prolonged intra-operative delay required for local delivery is avoided in this model. Furthermore, it may provide better protection of low frequency hearing than locally administered steroid.