Abnormal Cochlear Potentials in Friedreich's Ataxia Point to Disordered Synchrony of Auditory Nerve Fiber Activity

Santarelli, Rosamaria; Cama, Elona; Pegoraro, Elena; Scimemi, Pietro

doi:10.1159/000375307

Cited by 6 publications

(5 citation statements)

References 19 publications

(27 reference statements)

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“…Rance et al (2008) found reduced ABR Wave V/ I amplitude ratios (in patients who still had recordable potentials) consistent with axonal loss in the auditory nerve. Furthermore, Santarelli et al (2015b) carried out objective measures of auditory function in such patients and found summating potentials to be of normal latency but reduced amplitude and compound action potentials absent and replaced by a prolonged negativity, suggesting that Friedreich ataxia may also result in a reduction of inner hair cell function producing reduced depolarization of terminal dendrites.…”

Section: Axonal Neuropathiesmentioning

confidence: 99%

Pathophysiological mechanisms and functional hearing consequences of auditory neuropathy

Rance

Starr

2015

Brain

137

117

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The effects of inner ear abnormality on audibility have been explored since the early 20th century when sound detection measures were first used to define and quantify 'hearing loss'. The development in the 1970s of objective measures of cochlear hair cell function (cochlear microphonics, otoacoustic emissions, summating potentials) and auditory nerve/brainstem activity (auditory brainstem responses) have made it possible to distinguish both synaptic and auditory nerve disorders from sensory receptor loss. This distinction is critically important when considering aetiology and management. In this review we address the clinical and pathophysiological features of auditory neuropathy that distinguish site(s) of dysfunction. We describe the diagnostic criteria for: (i) presynaptic disorders affecting inner hair cells and ribbon synapses; (ii) postsynaptic disorders affecting unmyelinated auditory nerve dendrites; (iii) postsynaptic disorders affecting auditory ganglion cells and their myelinated axons and dendrites; and (iv) central neural pathway disorders affecting the auditory brainstem. We review data and principles to identify treatment options for affected patients and explore their benefits as a function of site of lesion.

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Section: Axonal Neuropathiesmentioning

confidence: 99%

Pathophysiological mechanisms and functional hearing consequences of auditory neuropathy

Rance

Starr

2015

Brain

137

117

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“…Psychoacoustic test batteries of speech and nonspeech stimuli are used to assess auditory processing in the central auditory nervous system. Temporal resolution (auditory temporal processing) is dependent on neural synchrony [ 24 ] and reported to be impaired in auditory neuropathy and FRDA patients [ 4 – 6 ]. Speech in noise test (auditory stream segregation) is also impaired in individuals with auditory neuropathy, FRDA [ 8 ] and brainstem pathology [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

“…Preneural auditory responses from the cochlear outer hair cells are typically normal in more than 90% of the patients [ 4 ]. Most of these individuals show abnormalities in auditory neural and brainstem responses as a result of axonopathy in the eighth nerve and auditory brainstem, termed as “auditory neuropathy,” [ 4 – 6 ] which is the cause of listening difficulties [ 4 , 7 , 8 ]. Patients with auditory neuropathy struggle to understand speech when background noise is present [ 9 , 10 ] and show impaired ability to selectively attend to a particular voice based on its location [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Auditory Phenotypic Variability in Friedreich’s Ataxia Patients

et al. 2021

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Auditory neural impairment is a key clinical feature of Friedreich’s Ataxia (FRDA). We aimed to characterize the phenotypical spectrum of the auditory impairment in FRDA in order to facilitate early identification and timely management of auditory impairment in FRDA patients and to explore the relationship between the severity of auditory impairment with genetic variables (the expansion size of GAA trinucleotide repeats, GAA1 and GAA2), when controlled for variables such as disease duration, severity of the disease and cognitive status. Twenty-seven patients with genetically confirmed FRDA underwent baseline audiological assessment (pure-tone audiometry, otoacoustic emissions, auditory brainstem response). Twenty of these patients had additional psychophysical auditory processing evaluation including an auditory temporal processing test (gaps in noise test) and a binaural speech perception test that assesses spatial processing (Listening in Spatialized Noise-Sentences Test). Auditory spatial and auditory temporal processing ability were significantly associated with the repeat length of GAA1. Patients with GAA1 greater than 500 repeats had more severe auditory temporal and spatial processing deficits, leading to poorer speech perception. Furthermore, the spatial processing ability was strongly correlated with the Montreal Cognitive Assessment (MoCA) score. To our knowledge, this is the first study to demonstrate an association between genotype and auditory spatial processing phenotype in patients with FRDA. Auditory temporal processing, neural sound conduction, spatial processing and speech perception were more severely affected in patients with GAA1 greater than 500 repeats. The results of our study may indicate that auditory deprivation plays a role in the development of mild cognitive impairment in FRDA patients.

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“…In addition to impaired balance and coordination of voluntary movements, Friedreich's ataxia is associated with hearing impairment, including difficulty understanding speech in background noise; auditory thresholds were, however, unchanged [88][89][90][91], nor was OHC function [92]. Most affected individuals show abnormalities in auditory neural and brainstem responses as a result of auditory neuropathy [92][93][94]. Of FRDA patients, 8 to 13% show sensorineural hearing loss, as revealed in a pure-tone audiogram [95].…”

Section: Friedreich's Ataxiamentioning

confidence: 99%

Current Advances in Gene Therapies of Genetic Auditory Neuropathy Spectrum Disorder

Saidia

Ruel

Bahloul

et al. 2023

JCM

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Auditory neuropathy spectrum disorder (ANSD) refers to a range of hearing impairments characterized by an impaired transmission of sound from the cochlea to the brain. This defect can be due to a lesion or defect in the inner hair cell (IHC), IHC ribbon synapse (e.g., pre-synaptic release of glutamate), postsynaptic terminals of the spiral ganglion neurons, or demyelination and axonal loss within the auditory nerve. To date, the only clinical treatment options for ANSD are hearing aids and cochlear implantation. However, despite the advances in hearing-aid and cochlear-implant technologies, the quality of perceived sound still cannot match that of the normal ear. Recent advanced genetic diagnostics and clinical audiology made it possible to identify the precise site of a lesion and to characterize the specific disease mechanisms of ANSD, thus bringing renewed hope to the treatment or prevention of auditory neurodegeneration. Moreover, genetic routes involving the replacement or corrective editing of mutant sequences or defected genes to repair damaged cells for the future restoration of hearing in deaf people are showing promise. In this review, we provide an update on recent discoveries in the molecular pathophysiology of genetic lesions, auditory synaptopathy and neuropathy, and gene-therapy research towards hearing restoration in rodent models and in clinical trials.

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Abnormal Cochlear Potentials in Friedreich's Ataxia Point to Disordered Synchrony of Auditory Nerve Fiber Activity

Abstract: These findings suggest that underlying auditory neuropathy in FRDA is a disordered synchrony in auditory nerve fiber discharge, possibly resulting from auditory nerve fiber degeneration and inner hair cell loss.

Cited by 6 publications

References 19 publications

Pathophysiological mechanisms and functional hearing consequences of auditory neuropathy

Pathophysiological mechanisms and functional hearing consequences of auditory neuropathy

Auditory Phenotypic Variability in Friedreich’s Ataxia Patients

Current Advances in Gene Therapies of Genetic Auditory Neuropathy Spectrum Disorder

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