Presynaptic and postsynaptic mechanisms underlying auditory neuropathy in patients with mutations in theOTOForOPA1gene

Rosamaria Santarelli,Roberta Rossi,Pietro Scimemi,Taosheng Huang,Ignacio Del Castillo,Elona Cama,Edoardo Arslan,Arnold Starr

doi:10.3109/1651386x.2011.558764

Rosamaria Santarelli, Roberta Rossi + Show 6 more

Open Access

https://doi.org/10.3109/1651386x.2011.558764

Copy DOI

Abstract

AbstractObjective: Our objective was to compare acoustically- and electrically-evoked potentials of the auditory nerve in patients with postsynaptic or presynaptic auditory neuropathy with underlying mutations in the OPA1 or OTOF gene. Study design: Transtympanic electrocochleography (ECochG) was recorded from two adult patients carrying the R445H OPA1 mutation, and from five children with mutations in the OTOF gene. Cochlear potentials to clicks or tone-bursts were compared to recordings obtained from 16 normally hearing subjects. Electrically-evoked neural responses recorded through the cochlear implant were also obtained. Results: The cochlear microphonic (CM) was recorded from all subjects, with normal amplitudes. After cancelling the CM, cochlear potentials were of negative polarity with reduced amplitude and prolonged duration compared to controls in both groups of patients. Prolonged negative responses were recorded as low as 50–90dB below behavioural threshold in subjects with OTOF mutations where...

Highlights

Auditory neuropathy (AN) is a disorder characterized by disruption of auditory nerve activity with preservation of outer hair cell (OHC) function [1]
Since in the majority of patients the SP was followed by a slow neural potential without an identifiable compound action potential (CAP), we indicated the waveform obtained after cochlear microphonic (CM) cancellation as the SP-CAP complex, and defined the SP-CAP onset at the initial negative deflection arising from baseline and the SP-CAP end at the return to baseline [15]
Cochlear potentials show an initial fast SP deflection followed by the CAP which returns to baseline by 2.4 ms

Summary

Introduction

Auditory neuropathy (AN) is a disorder characterized by disruption of auditory nerve activity with preservation of outer hair cell (OHC) function (otoacoustic emissions, OAE, and/or cochlear microphonic, CM) [1]. The disorder has a wide range of aetiologies (e.g. genetic, infectious, toxic-metabolic, immunological); in half the patients no aetiological factors can be identified [1,2]. It occurs in all age groups [1] and may be present in isolation or associated with multisystem involvement [1,3,4]. Among non-isolated AN disorders, mutations in the OPA1 gene are believed to cause disruption of auditory nerve discharge by affecting the unmyelinated portions of auditory nerve fibres [5]. Patients carrying OPA1 mutations present with slowly progressive loss of visual acuity, with underlying atrophy of optic nerve fibres; two-thirds show hearing

Methods

Results

Conclusion