[Peculiarities of CI processor fitting in children with auditory neuropathy spectrum disorders]. / Osobennosti nastroiki protsessora kokhlearnogo implantata u detei so slukhovoi (auditornoi) neiropatiei.

The peculiarities of cochlear implant (CI) processor fitting in children with auditory neuropathy spectrum disorders (ANSD) were investigated. At the 1-st fitting of the CI processor a standard protocol of parameters was used in all patients, including patients with cochlear nerve hypoplasia. After the initial fitting session, the behavioral tonal thresholds with CI in 55% of patients were 30-35 dB, in 32.% of patients - 40-50 dB. After 3-6 months, 65% of children with ANSD showed significant progress in auditory-speech development, which made it possible to use the standard protocol of tuning parameters for them with the most comfortable and threshold levels of electrical stimulation adjusted according to the child's reactions. The best dynamics was observed in 2 children with presynaptic ANSD with a confirmed DFNB9 (OTOF) gene mutation. In 35% of children, there was no progress in distinguishing speech signals and instability of reactions to sounds persisted after 6 months using of CI and speech therapy training, despite the low tonal thresholds of hearing. In these children the coding strategy was changed, the stimulation frequency was reduced, and the pulse width was increased. This helped to improve the discrimination of sounds with CI and progress in the child's speech development. The results demonstrate that children with ANSD require more frequent correction of CI processor settings: 1st year - every 3 months, then at least 2 times a year until the optimal coding strategy and settings are achieved. To predict the effectiveness of CI and determine the optimal tactics for setting up the CI processor in patients with ANSD, the preoperative examination should include MRI of the cerebellopontine angle to detect anomalies of the cochlear nerve and genetic examination to identify mutations that cause hearing impairment in patients with ANSD.

[The issue of auditory neuropathy: from origins to the present]. / Problema auditornoi (slukhovoi) neiropatii: ot istokov k sovremennosti.

The issue of auditory neuropathy spectrum disorders (ANSD) has been in a focus of specialists attention for a relatively short time, but during this time a huge amount of scientific and practical knowledge about this hearing disorder has been accumulated. ANSD is a specific auditory deficit caused by dysfunction of periphery part of the auditory system, which may affect the inner hair cells, the spiral ganglion neurons and the auditory nerve, as well as the area of synaptic contact between them, while the outer hair cells, as a rule, remain intact. As a result, a specific condition is formed, in which a patient's otoacoustic emissions and/or cochlear microphonics are present, auditory brainstem responses are abnormal or absent, electrophysiological data may not correlate with hearing level, the discrepancy between pure tone audiometry and speech discrimination is observed. ANSD prevalence, epidemiology, contemporary views on its etiology, including detailed information on hereditary forms of the disorder and its risk factors are considered in the review. The data on the basic rungs of the ANSD pathogenesis, which underlie the development of various forms of the disorder and mainly determine the rehabilitation approach, are presented. The detailed clinical and audiological characteristics of ANSD are presented; contemporary approach to ANSD diagnosis and rehabilitation, including indications for surgical treatment, are considered.

Cortical Auditory Event-Related Potentials and Categorical Perception of Voice Onset Time in Children With an Auditory Neuropathy Spectrum Disorder.

Objective: This study evaluated cortical encoding of voice onset time (VOT) in quiet and noise, and their potential associations with the behavioral categorical perception of VOT in children with auditory neuropathy spectrum disorder (ANSD). Design: Subjects were 11 children with ANSD ranging in age between 6.4 and 16.2 years. The stimulus was an /aba/-/apa/ vowel-consonant-vowel continuum comprising eight tokens with VOTs ranging from 0 ms (voiced endpoint) to 88 ms (voiceless endpoint). For speech in noise, speech tokens were mixed with the speech-shaped noise from the Hearing In Noise Test at a signal-to-noise ratio (SNR) of +5 dB. Speech-evoked auditory event-related potentials (ERPs) and behavioral categorization perception of VOT were measured in quiet in all subjects, and at an SNR of +5 dB in seven subjects. The stimuli were presented at 35 dB SL (re: pure tone average) or 115 dB SPL if this limit was less than 35 dB SL. In addition to the onset response, the auditory change complex (ACC) elicited by VOT was recorded in eight subjects. Results: Speech evoked ERPs recorded in all subjects consisted of a vertex positive peak (i.e., P1), followed by a trough occurring approximately 100 ms later (i.e., N2). For results measured in quiet, there was no significant difference in categorical boundaries estimated using ERP measures and behavioral procedures. Categorical boundaries estimated in quiet using both ERP and behavioral measures closely correlated with the most-recently measured Phonetically Balanced Kindergarten (PBK) scores. Adding a competing background noise did not affect categorical boundaries estimated using either behavioral or ERP procedures in three subjects. For the other four subjects, categorical boundaries estimated in noise using behavioral measures were prolonged. However, adding background noise only increased categorical boundaries measured using ERPs in three out of these four subjects. Conclusions: VCV continuum can be used to evaluate behavioral identification and the neural encoding of VOT in children with ANSD. In quiet, categorical boundaries of VOT estimated using behavioral measures and ERP recordings are closely associated with speech recognition performance in children with ANSD. Underlying mechanisms for excessive speech perception deficits in noise may vary for individual patients with ANSD.

A case of auditory neuropathy revealed by OTOF gene mutation analysis in a junior high school girl.

OBJECTIVE: Congenital auditory neuropathy (AN) affects hearing and speech development. The degree of hearing difficulty in congenital AN varies as a function of pathology at the inner ear hair cell (IHC) synapses or the auditory nerve. We report a case of a Chinese girl with AN revealed by OTOF (otoferlin) gene mutation analysis who had only a mild hearing loss. PATIENT: A 13-year-old Chinese girl was diagnosed as having congenital AN on the basis of OTOF gene mutation analysis. She manifest a mild sensorineural hearing loss with 50% maximum monosyllable speech discrimination rate, normal DPOAEs (distortion product otoacoustic emissions) beyond ambient noise levels, only SPs (summating potentials) evoked during ECoG (electrocochleography) and absent ABRs (auditory evoked brainstem responses) bilaterally to clicks presented at 100 dBnHL. She was able to effectively communicate with others by speech reading owing to her mild hearing loss. Moreover, bilateral hearing aids helped her to communicate. CONCLUSIONS: Our patient was demonstrated to have a mutation on the OTOF gene. Nevertheless, she was able to communicate using auditory visual speech reading in spite of a mild auditory threshold elevation probably due to partial pathology at the IHC synapses or in the auditory nerve.

Management of children with auditory neuropathy spectrum disorder (ANSD) / Tratamento de crianças com espectro da neuropatia auditiva (ENA)

ABSTRACT INTRODUCTION: ANSD is a challenging problem. OBJECTIVE: To present our experience on management of the children with ANSD with respect to clinical data. METHODS: This retrospective study included all children younger than 16 years of age who applied to the department between 2005 and 2013 (with the exception of newborn hearing screening NHS referrals). The data were derived from pure tone, OAEs and ABR tests, and further medical risk factors of the subjects were evaluated. RESULTS: ANSD was recognized in 74 ears of 40 children (B/U: 34/6) among 1952 children with SNHL (2.04%) detected among 9520 applicants to the department (0.42%). The clinical tests revealed that hearing loss greater than 15 dB was present in both ears of 38 cases. The degree of hearing loss was profound in 48% children, severe in 12% children, moderate in 28% children, mild in 10% children and normal in 5% children. ABRs were absent/abnormal in 37/3 ears and CMs were detected in all. Acoustic reflexes were absent in all ears. Rehabilitation was managed by CI and hearing aids in 15 and 23 cases, respectively. FM system was given to two cases displaying normal hearing but poor speech discrimination in noisy environments. CONCLUSION: ANSD is a relatively challenging problem for the audiology departments because of its various clinical features and difficulties in management. Our patients with ANSD most commonly displayed profound hearing loss. The number of overlooked cases may be minimized by performing ABR and OAE in every case referred with the suspicion of hearing loss.

Resumo Introdução: Espectro da neuropatia auditiva ainda é uma condição clínica desafiadora. Objetivo: Apresentar nossa experiência no tratamento de crianças com espectro da neuropatia auditiva em relação aos dados clínicos. Método: Este estudo retrospectivo incluiu crianças menores de 16 anos de idade que deram entrada no departamento entre 2005 e 2013 (com exceção de encaminhamentos para triagem auditiva neonatal). Foram avaliados os dados obtidos a partir dos exames de audiometria tonal, emissões otoacústicas (EOA), potencial evocado auditivo de tronco encefálico (ABR) e outros fatores de risco. Resultados: Das 1.952 crianças com perda auditiva neurossensorial (2,04%) detectadas dentre os 9.520 candidatos que deram entrada no departamento (0,42%), espectro da neuropatia auditiva foi reconhecida em 74 orelhas de 40 crianças (B/U: 34/6). Os testes clínicos revelaram que uma perda auditiva superior a 15 dB estava presente em ambas as orelhas em 38 casos. O grau de perda auditiva das crianças era profundo em 48%, grave em 12%, moderado em 28%, leve em 10%, e normal em 5%. ABR estava ausente/anormal em 37/3 orelhas e microfonia coclear foi detectado em todas as crianças. Reflexos acústicos estavam ausentes em todas as orelhas. A reabilitação foi tratada com implante coclear e aparelhos auditivos em 15 e 23 casos, respectivamente. Um sistema FM foi utilizado em dois casos que apresentavam audição normal, mas discriminação deficiente da fala em ambientes ruidosos. Conclusão: Espectro da neuropatia auditiva é um problema desafiador para os departamentos de audiologia, devido às suas várias características clínicas e dificuldades no tratamento. Em nossos pacientes a perda auditiva profunda foi a mais frequente. O número de casos negligenciados pode ser diminuído com a realização dos exames ABR e EOA em todos os casos encaminhados com suspeita de perda auditiva.

Management of children with auditory neuropathy spectrum disorder (ANSD).

INTRODUCTION: ANSD is a challenging problem. OBJECTIVE: To present our experience on management of the children with ANSD with respect to clinical data. METHODS: This retrospective study included all children younger than 16 years of age who applied to the department between 2005 and 2013 (with the exception of newborn hearing screening NHS referrals). The data were derived from pure tone, OAEs and ABR tests, and further medical risk factors of the subjects were evaluated. RESULTS: ANSD was recognized in 74 ears of 40 children (B/U: 34/6) among 1952 children with SNHL (2.04%) detected among 9520 applicants to the department (0.42%). The clinical tests revealed that hearing loss greater than 15dB was present in both ears of 38 cases. The degree of hearing loss was profound in 48% children, severe in 12% children, moderate in 28% children, mild in 10% children and normal in 5% children. ABRs were absent/abnormal in 37/3 ears and CMs were detected in all. Acoustic reflexes were absent in all ears. Rehabilitation was managed by CI and hearing aids in 15 and 23 cases, respectively. FM system was given to two cases displaying normal hearing but poor speech discrimination in noisy environments. CONCLUSION: ANSD is a relatively challenging problem for the audiology departments because of its various clinical features and difficulties in management. Our patients with ANSD most commonly displayed profound hearing loss. The number of overlooked cases may be minimized by performing ABR and OAE in every case referred with the suspicion of hearing loss.

Auditory nerve disease and auditory neuropathy spectrum disorders.

In 1996, a new type of bilateral hearing disorder was discerned and published almost simultaneously by Kaga et al. [1] and Starr et al. [2]. Although the pathophysiology of this disorder as reported by each author was essentially identical, Kaga used the term "auditory nerve disease" and Starr used the term "auditory neuropathy". Auditory neuropathy (AN) in adults is an acquired disorder characterized by mild-to-moderate pure-tone hearing loss, poor speech discrimination, and absence of the auditory brainstem response (ABR) all in the presence of normal cochlear outer hair cell function as indicated by normal distortion product otoacoustic emissions (DPOAEs) and evoked summating potentials (SPs) by electrocochleography (ECoG). A variety of processes and etiologies are thought to be involved in its pathophysiology including mutations of the OTOF and/or OPA1 genes. Most of the subsequent reports in the literature discuss the various auditory profiles of patients with AN [3,4] and in this report we present the profiles of an additional 17 cases of adult AN. Cochlear implants are useful for the reacquisition of hearing in adult AN although hearing aids are ineffective. In 2008, the new term of Auditory Neuropathy Spectrum Disorders (ANSD) was proposed by the Colorado Children's Hospital group following a comprehensive study of newborn hearing test results. When ABRs were absent and DPOAEs were present in particular cases during newborn screening they were classified as ANSD. In 2013, our group in the Tokyo Medical Center classified ANSD into three types by following changes in ABRs and DPOAEs over time with development. In Type I, there is normalization of hearing over time, Type II shows a change into profound hearing loss and Type III is true auditory neuropathy (AN). We emphasize that, in adults, ANSD is not the same as AN.

Identification of novel OTOF compound heterozygous mutations by targeted next-generation sequencing in a Chinese patient with auditory neuropathy spectrum disorder.

OBJECTIVES: The molecular causes of auditory neuropathy spectrum disorder (ANSD) are not well known. Identification of the pathogenic mutations underlying nonsyndromic ANSD is difficult because of its extremely heterogeneous trait. The aim of the present study was to identify the genetic etiology of a single Chinese patient diagnosed with congenital ANSD by targeted next-generation sequencing. METHODS: Targeted next-generation sequencing of 79 known deafness genes was performed in a child that was clinically diagnosed with ANSD and received cochlear implantation. Candidate pathogenic variants were confirmed by Sanger sequencing. Post-implantation outcome were evaluated in a 40 months span. RESULTS: Novel compound heterozygous mutations p.R1583H/p.Q1883X in OTOF were identified as the pathogenic cause of the patient, correlated with a good post-implantation outcome in terms of sound detection and communication skills. CONCLUSION: Targeted next-generation sequencing is effective for molecular diagnosis of ANSD and may provide important information for clinical management of this disease.