THE DEPARTMENT OF SPEECH PATHOLOGY AND AUDIOLOGY. FACULTY OF ARTS, UNIVERSITY OF THE WITWATERSRAND, JOHANNESBURG In partial fulfillment of the requirements for the degree of Master of Arts by coursework in Audiology June 1999 / High stimulus repetition rates have been proposed as a solution to the poor sensitivity and specificity of the standard electrocochleogram. The use of this approach has been confounded, however, by conflicting literature reports on the effects of high stimulus repetition rates on normal subjects. This study aimed to confirm the effects of high stimulus repetition rates on normal hearing subjects as a precursor to clinical high stimulus repetition rate electrocochleography trials. Electrocochleogram tracings were recorded binaurally from 51 normal hearing subjects at 7.1 cps, 51.1 cps, 101.1 cps and 151.1 cps and the summating potential and action potential latencies and amplitudes, summating potential/action potential amplitude ratios and waveform widths were recorded. Statistical analyses showed that increasing the stimulus repetition rate caused statistically (p<O.05) and clinically (p<O.O1 for latency and p<O.005 for amplitude) significant changes to the action potential latency and amplitude, summating potential/action potential amplitude ratio and waveform width, but caused only limited statistical (p<O.05) and clinical (p<O.OI for latency and p<O.005 for amplitude) changes to the summating potential amplitude and latency. Subject age had no effect on the results and there was no interaction between age and stimulus repetition rates. These findings provide the most comprehensive data on the effects of fast stimulus repetition rates to date, and have provided the beginnings of a valid clinical normative database for high stimulus repetition rate tympanic electrode electrocochleography.

Vertigo is the presenting symptom of some peripheral vestibular disorders, like Benign Positional Vertigo (BPV), Ménière's disease, and vestibular neuritis, and for many other clinical conditions as well. Some clinicians from the Christchurch Public Hospital suspect that there is a significant need to improve the diagnostic accuracy and overall management of patients presenting with complaints of "acute vertigo or dizziness", especially BPV and Ménière's disease. The final diagnosis of many such patients treated for these conditions in the past has been suspected to be somewhat incomplete or inappropriate. These patients were commonly referred to various other departments, where they underwent a number of investigations, particularly medical imaging [head CT (Computed Tomography) / MRI (Magnetic Resonance Imaging) scans, which were in many cases not necessary. Such delays in the process led to an extra or unnecessary burden on the limited health funds available to the hospital or to the patient. Another drawback was an elevated patient stress and anxiety as critical time was lost with the increased number of admissions, or in transferring the patient between various departments without any conclusive diagnosis and treatment. It was proposed to conduct a retrospective study on the accuracy of diagnosis of those patients admitted to Christchurch Public Hospital with complaints of acute vertigo, particularly for suspected peripheral vestibular disorders (mainly BPV and Ménière's disease) over the period of 2004-2005. Implementation of a more specific and detailed management approach at the level of the initial clinical examination or diagnostic investigations (specifically, by an early Otolaryngology/Audiology intervention) was planned for the year 2006. The two groups of patients (2004-2005 and 2006) were compared to verify the final achievements concerning the diagnostic accuracy and at various other levels with the newly implemented changes in 2006.

Vertigo is the presenting symptom of some peripheral vestibular disorders, like Benign Positional Vertigo (BPV), Ménière's disease, and vestibular neuritis, and for many other clinical conditions as well. Some clinicians from the Christchurch Public Hospital suspect that there is a significant need to improve the diagnostic accuracy and overall management of patients presenting with complaints of "acute vertigo or dizziness", especially BPV and Ménière's disease. The final diagnosis of many such patients treated for these conditions in the past has been suspected to be somewhat incomplete or inappropriate. These patients were commonly referred to various other departments, where they underwent a number of investigations, particularly medical imaging [head CT (Computed Tomography) / MRI (Magnetic Resonance Imaging) scans, which were in many cases not necessary. Such delays in the process led to an extra or unnecessary burden on the limited health funds available to the hospital or to the patient. Another drawback was an elevated patient stress and anxiety as critical time was lost with the increased number of admissions, or in transferring the patient between various departments without any conclusive diagnosis and treatment. It was proposed to conduct a retrospective study on the accuracy of diagnosis of those patients admitted to Christchurch Public Hospital with complaints of acute vertigo, particularly for suspected peripheral vestibular disorders (mainly BPV and Ménière's disease) over the period of 2004-2005. Implementation of a more specific and detailed management approach at the level of the initial clinical examination or diagnostic investigations (specifically, by an early Otolaryngology/Audiology intervention) was planned for the year 2006. The two groups of patients (2004-2005 and 2006) were compared to verify the final achievements concerning the diagnostic accuracy and at various other levels with the newly implemented changes in 2006.

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Objectifs: La pathophysiologie de la maladie de Ménière (MM) demeure mal comprise. Nous avons identifié dans la littérature un groupe de protéines exprimées sur le sac endolymphatique (SEL) et impliquées dans la régulation du volume endolymphatique : l’Aquaporine-2 (AQP2), le récepteur V2R de vasopressine (AVP), le Co-transporteur de Sodium Potassium et Chlorure type 2 (NKCC2) et le canal TRP type V4 (TRPV4). Notre objectif est de déterminer si leur expression sur le SEL est altérée dans la MM, pour améliorer notre compréhension de la physiologie de l’hydrops endolymphatique. Méthodes: Recrutement des cas de MM et schwannomes vestibulaires (SV) comme contrôles, le jour de leurs chirurgies respectives. Prélèvement de biopsies de SEL et sang pour AVP. L’immunohistochimie pour AQP2, V2R, NKCC2 et TRPV4 fut effectuée, et les lames scannées pour analyse digitale de densité d’expression par un logiciel spécialisé (VIS par Visiopharm®). Résultats: Total de 27 cas MM et 23 contrôles. Les scores générés par le logiciel représentent la densité d’expression totale et relative des protéines, exclusivement sur l’épithélium du SEL. Les scores d’AQP2 sont élevés de façon significative dans la MM comparée aux contrôles (p = 0.018). Nous ne rapportons aucune variation significative pour AVP, V2R, NKCC2 et TRPV4. Conclusion: Cette étude originale évalue l’expression simultanée de AQP2, V2R, NKCC2 et TRPV4 sur le SEL dans la MM, avec un groupe contrôle (SV). Nos résultats démontrent une augmentation isolée de l’AQP2 dans la MM. Nous proposons une surexpression constitutive de cette dernière, indépendante de son axe de régulation (AVP-V2R). Une mutation somatique au niveau des séquences régulatrices pourrait justifier nos observations. / Objectives: Endolymphatic sac (ELS) pathophysiology in Ménière’s Disease (MD) remains poorly understood. We identified from the literature a group of proteins expressed on the ELS and involved in endolymph volume regulation: Aquaporin-2 (AQP2), vasopressin receptor V2R, Sodium Potassium Chloride Cotransporter type 2 (NKCC2) and TRP channel type V4 (TRPV4). Our objective was to determine whether their ELS expression was altered in MD, to better understand the pathophysiology of endolymphatic hydrops. Methods: Patients with definite MD undergoing endolymphatic duct blockage surgery were recruited, as well as controls undergoing surgery for vestibular schwannomas (VS). ELS biopsies and blood samples for plasma Arginine Vasopressin (AVP) were obtained. Immunohistochemistry for AQP2, V2R, NKCC2 and TRPV4 was performed. Slides were scanned digitally for highly sensitive pixel density analysis by specialized software (VIS by Visiopharm®). Results: 27 definite MD patients and 23 VS controls were included. Global scores generated by the software represent total and relative protein expression density of 3 staining intensity levels, exclusively on ELS epithelium. AQP2 expression density was significantly elevated in MD compared to VS (p = 0.018). There was no significant difference in plasma AVP, V2R, NKCC2 and TRPV4 expression. Conclusion: This original study evaluates simultaneous in-situ expression of AQP2, V2R, NKCC2 and TRPV4 on the human ELS in MD, with a VS control group. Our results show only AQP2 up regulation on the ELS of MD patients. We suggest a constitutively increased expression of AQP2 in MD, independent of its regulatory axis (AVP-V2R). Acquired regulator sequence mutations could support this model.