Information from cochlear potentials and genetic mutations helps localize the lesion site in auditory neuropathy

Auditory neuropathy (AN) is a disorder characterized by disruption of auditory nerve activity resulting from lesions involving the auditory nerve (postsynaptic AN), inner hair cells and/or the synapses with auditory nerve terminals (presynaptic AN). Affected subjects show impairment of speech perception beyond that expected for the hearing loss, abnormality of auditory brainstem potentials and preserved outer hair-cell activities. Furthermore, AN can be identified either as an isolated disorder or as an associated disorder with multisystem involvement including peripheral and optic neuropathies (non-isolated AN). Mutations in several nuclear and mitochondrial genes have been identified as underlying these forms of AN. Recently, new genes have been identified as involved in both isolated (DIAPH3, OTOF) and non-isolated AN (OPA1). Moreover, abnormal cochlear potentials have been recorded from patients with specific gene mutations by using acoustic stimuli or electrical stimulation through cochlear implant. In this review, different types of genetically based auditory neuropathies are discussed and the proposed molecular mechanisms underlying AN are reviewed

Hearing Dysfunction in a Large Family Affected by Dominant Optic Atrophy (OPA8-Related DOA): A Human Model of Hidden Auditory Neuropathy

Hidden auditory neuropathy is characterized by reduced performances in challenging auditory tasks with the preservation of hearing thresholds, resulting from diffuse loss of cochlear inner hair cell (IHC) synapses following primary degeneration of unmyelinated terminals of auditory fibers. We report the audiological and electrophysiological findings collected from 10 members (4 males, 6 females) of a large Italian family affected by dominant optic atrophy, associated with the OPA8 locus, who complained of difficulties in understanding speech in the presence of noise. The patients were pooled into two groups, one consisting of 4 young adults (19–50 years) with normal hearing thresholds, and the other made up of 6 patients of an older age (55–72 years) showing mild hearing loss. Speech perception scores were normal in the first group and decreased in the second. Otoacoustic emissions (OAEs) and cochlear microphonics (CMs) recordings were consistent with preservation of outer hair cell (OHC) function in all patients, whereas auditory brainstem responses (ABRs) showed attenuated amplitudes in the first group and severe abnormalities in the second. Middle ear acoustic reflexes had delayed peak latencies in all patients in comparison with normally hearing individuals. Transtympanic electrocochleography (ECochG) recordings in response to 0.1 ms clicks at intensities from 120 to 60 dB peak equivalent SPL showed a reduction in amplitude of both summating potential (SP) and compound action potential (CAP) together with delayed CAP peak latencies and prolonged CAP duration in all patients in comparison with a control group of 20 normally hearing individuals. These findings indicate that underlying the hearing impairment in OPA8 patients is hidden AN resulting from diffuse loss of IHCs synapses. At an early stage the functional alterations only consist of abnormalities of ABR and ECochG potentials with increased latencies of acoustic reflexes, whereas reduction in speech perception scores become apparent with progression of the disease. Central mechanisms increasing the cortical gain are likely to compensate for the reduction of cochlear input

OPA1-related auditory neuropathy: site of lesion and outcome of cochlear implantation.

Hearing impairment is the second most prevalent clinical feature after optic atrophy in Dominant Optic Atrophy associated with mutations in the OPA1 gene. In this study we characterized the hearing dysfunction in OPA1-linked disorders and provided effective rehabilitative options to improve speech perception. We studied two groups of OPA1 subjects, one comprising 11 patients (7 males; age range 13-79 years) carrying OPA1 mutations inducing haploinsufficiency, the other, 10 subjects (3 males; age range 5-58 years) carrying OPA1 missense mutations. Both groups underwent audiometric assessment with pure tone and speech perception evaluation, and otoacoustic emissions and auditory brainstem response recording. Cochlear potentials were recorded through transtympanic electrocochleography from the group of patients harboring OPA1 missense mutations and were compared to recordings obtained from 20 normally-hearing controls and from 19 subjects with cochlear hearing loss. Eight patients carrying OPA1 missense mutations underwent cochlear implantation. Speech perception measures and electrically-evoked auditory nerve and brainstem responses were obtained after one year of cochlear implant use. Nine out of 11 patients carrying OPA1 mutations inducing haploinsufficiency had normal hearing function. In contrast, all but one subject harboring OPA1 missense mutations displayed impaired speech perception, abnormal brainstem responses and presence of otoacoustic emissions consistent with auditory neuropathy. In electrocochleography recordings, cochlear microphonic had enhanced amplitudes while summating potential showed normal latency and peak amplitude consistent with preservation of both outer and inner hair cell activities. After cancelling the cochlear microphonic, the synchronized neural response seen in both normally-hearing controls and subjects with cochlear hearing loss was replaced by a prolonged, low-amplitude negative potential that decreased in both amplitude and duration during rapid stimulation consistent with neural generation. The use of cochlear implant improved speech perception in all but one patient. Brainstem potentials were recorded in response to electrical stimulation in five subjects out of six, whereas no compound action potential was evoked from the auditory nerve through the cochlear implant. These findings indicate that underlying the hearing impairment in patients carrying OPA1 missense mutations is a disordered synchrony in auditory nerve fiber activity resulting from neural degeneration affecting the terminal dendrites. Cochlear implantation improves speech perception and synchronous activation of auditory pathways by by-passing the site of lesion

An audiological perspective on ''Two further patients with Warsaw breakage syndrome. Is a mild phenotype possible?"

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A European perspective on auditory processing disorder-current knowledge and future research focus

Current notions of \u201chearing impairment,\u201d as reflected in clinical audiological practice, do not acknowledge the needs of individuals who have normal hearing pure tone sensitivity but who experience auditory processing difficulties in everyday life that are indexed by reduced performance in other more sophisticated audiometric tests such as speech audiometry in noise or complex non-speech sound perception. This disorder, defined as \u201cAuditory Processing Disorder\u201d (APD) or \u201cCentral Auditory Processing Disorder\u201d is classified in the current tenth version of the International Classification of diseases as H93.25 and in the forthcoming beta eleventh version. APDs may have detrimental effects on the affected individual, with low esteem, anxiety, and depression, and symptoms may remain into adulthood. These disorders may interfere with learning per se and with communication, social, emotional, and academic-work aspects of life. The objective of the present paper is to define a baseline European APD consensus formulated by experienced clinicians and researchers in this specific field of human auditory science. A secondary aim is to identify issues that future research needs to address in order to further clarify the nature of APD and thus assist in optimumdiagnosis and evidence-based management. This European consensus presents the main symptoms, conditions, and specific medical history elements that should lead to auditory processing evaluation. Consensus on definition of the disorder, optimum diagnostic pathway, and appropriate management are highlighted alongside a perspective on future research focus

Speech Perception Changes in the Acoustically Aided, Nonimplanted Ear after Cochlear Implantation: A Multicenter Study

In recent years there has been an increasing percentage of cochlear implant (CI) users who have usable residual hearing in the contralateral, nonimplanted ear, typically aided by acoustic amplification. This raises the issue of the extent to which the signal presented through the cochlear implant may influence how listeners process information in the acoustically stimulated ear. This multicenter retrospective study examined pre- to postoperative changes in speech perception in the nonimplanted ear, the implanted ear, and both together. Results in the latter two conditions showed the expected increases, but speech perception in the nonimplanted ear showed a modest yet meaningful decrease that could not be completely explained by changes in unaided thresholds, hearing aid malfunction, or several other demographic variables. Decreases in speech perception in the nonimplanted ear were more likely in individuals who had better levels of speech perception in the implanted ear, and in those who had better speech perception in the implanted than in the nonimplanted ear. This raises the possibility that, in some cases, bimodal listeners may rely on the higher quality signal provided by the implant and may disregard or even neglect the input provided by the nonimplanted ear

La neuropatia uditiva

Nel corso degli ultimi decenni le alterazioni della percezione verbale causate da una disfunzione del sistema uditivo non riconducibili a una lesione cocleare \u201cclassica\u201d sono state oggetto di un crescente interesse emergendo dal gruppo indistinto ed eterogeneo dei disturbi psichiatrici, neuropsicologici e del linguaggio in cui erano state confinate. La spinta alla individuazione di alterazioni del \u201cprocessing\u201d del segnale uditivo si \ue8 svolta lungo due direttive principali. Nel 1996 Arnold Starr e collaboratori hanno riportato le caratteristiche cliniche di un gruppo di pazienti che presentavano una severa compromissione della percezione verbale a fronte di una perdita uditiva lieve o moderata. Tali reperti erano associati alla presenza delle otoemissioni acustiche (otoacoustic emissions, OAEs) e all\u2019assenza delle risposte evocate uditive del tronco encefalico (auditory brainstem responses, ABRs). L\u2019assenza di coinvolgimento del sistema nervoso centrale e il riscontro di una neuropatia periferica riscontrate nella maggioranza dei pazienti ha indotto gli autori a ipotizzare che la lesione responsabile della compromissione della percezione verbale e dell\u2019assenza della risposta ABR fosse riconducibile a fenomeni di demielinizzazione delle fibre del nervo uditivo (auditory neuropathy, AN) o in alternativa, a lesioni delle cellule ciliate interne (inner hair cells, IHCs) o delle sinapsi interposte. Le basi neurofisiologiche della ridotta percezione verbale sarebbero pertanto da ricercare in una alterata codifica dell\u2019informazione uditiva da parte del compartimento afferente periferico con conservazione della funzionalit\ue0 delle cellule ciliate esterne (outer hair cells. OHCs)

Meccanismi neurofisiologici alla base degli acufeni: effetti inaspettati della plasticit\ue0\ua0 neuronale

Classicamente gli acufeni sono stati classificati in periferici e centrali sulla base della presunta localizzazione della lesione a livello della periferia uditiva o del sistema nervoso centrale. Tale lesione determinerebbe l\u2019insorgenza di un segnale neurale \u201caberrante\u201d responsabile della erronea percezione sonora (Eggermont, 2003; Baguley, 2002). In realt\ue0, il problema \ue8 troppo complesso per poter essere risolto in questi termini. I dati forniti dalla ricerca di base e dalla ricerca clinica inducono attualmente a ritenere che nella stragrande maggioranza dei casi la lesione debba essere localizzata a livello della periferia uditiva e riguardi in particolare le cellule ciliate (Nore\uf1a e Eggermont, 2003, Jastreboff, 1990; Liberman e Kiang, 1978). La conseguente modificazione del pattern di scarica a livello delle fibre del nervo rappresenta comunque una condizione necessaria ma non sufficiente per l\u2019insorgenza di una illusione della percezione uditiva. La realizzazione di questa condizione dipende infatti strettamente dalle modalit\ue0 con cui la nuova configurazione della scarica neurale periferica viene elaborata dai centri nervosi immediatamente dopo l\u2019instaurarsi del danno e, in una fase successiva, dopo l\u2019innesco dei fenomeni di plasticit\ue0 neuronale

Hearing aids for auditory neuropathy patients

Auditory Neuropathy (AN) is a hearing disorder characterized by disruption of temporal coding of acoustic signals in auditory nerve fibers resulting from lesions involving the nerve fibers themselves, the inner hair cells or their synapses with auditory nerve terminals. In contrast, outer hair cell activities are preserved (cochlear microphonic and otoacoustic emissions, OAEs). AN may be underlain by genetic disorders or result from a wide range of other etiologies. The disruption of auditory nerve discharge underlies both the absence of auditory brainstem responses (ABRs) and the impairment of speech perception. These alterations show high variability depending on etiology, site of lesion and stage of the disease. Cochlear implantation constitutes the only rehabilitative tool able to restore speech perception in patients with genetic AN. Nevertheless, some patients benefit from the use of auditory input delivered by hearing aids before cochlear implantation. Differently from subjects affected by genetic AN, hearing-impaired children discharged from Neonatal Intensive Care Units (NICUs) with absent ABRs and presence of OAEs may be successful hearing aid users. In this presentation I shall report the outcome of hearing aid use in patients with genetic AN and in a group of children discharged from NICUs with the clinical picture of AN