AIFM1 variants associated with auditory neuropathy spectrum disorder cause apoptosis due to impaired apoptosis-inducing factor dimerization / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.‍T260A, p.‍R422W, and p.‍R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%‍‒‍49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%‍‒‍17.9%, which was significantly higher than that (6.9%‍‒‍7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.

Etiology of early hearing loss in Brazilian children / Etiologia da perda auditiva precoce em crianças brasileiras

Abstract Introduction Hearing loss etiology depends on the population studied as well as on the ethnicity and the socio-economic condition of the analyzed region. Etiological diagnosis contributes to the improvement of preventive measures and to the early identification of this deficiency. Objective To identify the etiological factors of hearing loss and its prevalence in a tertiary hospital in southern Brazil, to verify the frequency of mutations in GJB2 and GJB6 genes, and to correlate the degree of hearing loss with the etiological factors of deafness. Methods This prevalence study involved 140 children with bilateral sensorineural or mixed hearing loss. Medical history, physical examination, audiometry, and evoked auditory brainstem response were conducted. Imaging and genetic examinations were also performed. Results Etiologies and their prevalence were as follows: (a) indeterminate causes, 31.4%; (b) conditions related to neonatal period, 22.1%; (c) genetic, 22.1%; (d) auditory neuropathy, 10%; (e) other factors (cortical malformation, intracranial hemorrhage, and internal ear malformations), 7.9% and (f) congenital infections, 6.4%. Within the genetic cases, ten homozygous and seven heterozygotes of the 35delG mutation were identified, besides two cases of rare variants of GJB2: p.Try172* and p.Arg184Pro. One case with homozygosis of del(GJB6-D13S1830) was found. Regarding severity of hearing loss, in 78.6% of the cases the degree of hearing loss was profound and there were no significant differences when comparing between etiologies. Conclusion The number of indeterminate etiologies is still high and congenital CMV infection may be a possible cause of undiagnosed etiology for hearing loss. The predominance of etiologies related to neonatal conditions and infectious causes are characteristic of developing countries. The most prevalent mutation was 35delG, the main GJB2 gene, probably because of the European influence in the genotype of our population.

Resumo Introdução A etiologia da perda auditiva depende da população estudada, da etnia e da condição socioeconômica da região analisada. O diagnóstico etiológico contribui para o aprimoramento das medidas preventivas e para a identificação precoce dessa deficiência. Objetivos Identificar os fatores etiológicos da perda auditiva e sua prevalência em um hospital terciário do sul do Brasil, verificar a frequência de mutações nos genes GJB2 e GJB6 e correlacionar o grau da perda auditiva com os fatores etiológicos da deficiência auditiva. Método Este estudo de prevalência avaliou 140 crianças com perda auditiva neurossensorial bilateral ou mista. Foram submetidos a anamnese com histórico médico, exame físico, audiometria e potencial evocado auditivo de tronco encefálico. Exames de imagem e genéticos também foram feitos. Resultados As etiologias e sua prevalência foram as seguintes: (a) causas indeterminadas, 31,4%; (b) condições relacionadas ao período neonatal, 22,1%; (c) genética, 22,1%; (d) neuropatia auditiva, 10%; (e) outros fatores (malformação cortical, hemorragia intracraniana e malformações da orelha interna), 7,9% e (f) infecções congênitas, 6,4%. Entre os casos genéticos, foram identificados dez casos homozigotos e sete heterozigotos da mutação 35delG, além de dois casos de variantes raras do GJB2: p.Try172* e p.Arg184Pro. Foi encontrado um caso homozigoto da mutação del (GJB6‐D13S1830). Em relação à gravidade da perda auditiva, em 78,6% dos casos o grau da perda auditiva foi profundo e não houve diferenças significantes na comparação entre as etiologias. Conclusão O número de etiologias indeterminadas ainda é elevado e a infecção congênita por CMV pode ser uma possível causa de etiologia não diagnosticada para perda auditiva. A predominância das etiologias relacionadas às condições neonatais e às causas infecciosas são características de países em desenvolvimento. A mutação mais prevalente foi a 35delG e o principal gene foi o GJB2, provavelmente devido à influência europeia no genótipo de nossa população.

Effect of Quiet and Noise on P300 Response in Individuals with Auditory Neuropathy Spectrum Disorder

Abstract Introduction Auditory neuropathy spectrum disorder (ANSD) is a clinical condition in which individuals have normal cochlear responses and abnormal neural responses. There is a lack of evidence in the literature regarding the neural discrimination skill in individuals with ANSD, especially when the signal is presented in the presence of noise. Objectives The present study was performed with the aim to investigate auditory discrimination skill, in quiet and in the presence of noise, in individuals with ANSD and to compare the findings with normal-hearing individuals. Methods A total of 30 individuals with normal hearing sensitivity and 30 individuals with ANSD in the age range of 15 to 55 years old, with the mean age of 27.86 years old, were the participants. P300 response was recorded from both groups using syllable pairs /ba/-/da/ in oddball paradigm and the syllable /da/ in repetitive paradigm in quiet and at +10 dB signal-to-noise ratio (SNR). Results There was significant prolongation in latency and reaction time, and reduction in amplitude of P300 response and sensitivity in both groups with the addition of noise. The topographic pattern analysis showed activation of the central-parietal-occipital region of the brain in individuals with ANSD, whereas activation of the central-parietal region was observed in individuals with normal hearing. The activation was more diffused in individuals with ANSD compared with that of individuals with normal hearing. Conclusion The individuals with ANSD showed a significantly more adverse effect of noise on the neural discrimination skill than the normal counterpart.

Importance of Vestibulo-ocular Reflex Gain and Refixation Saccade Analysis in Individuals with Auditory Neuropathy Spectrum Disorder

Abstract Introduction Auditory neuropathy spectrum disorder (ANSD) features the presence of otoacoustic emissions, poor speech identification score and absent auditory brainstem response. Objective The present study was designed to evaluate the functioning of all six semicircular canals in individuals with ANSD and to compare it with those of normalhearing individuals. Methods A total of 50 individuals participated in the present study, in which Group I comprised25normal-hearingindividuals, and GroupII comprised25individualswithANSD. All of the participants underwent case history, pure tone audiometry, immittance, otoacoustic emissions, auditory evoked response and video head impulse test (vHIT). Results The independent sample t-test revealed significantly lower vestibulo-ocular reflex gain values in individuals with ANSD. A presence of 100% corrective refixation saccades was observed in the same group. The Pearson correlation test revealed no significant correlation between vestibulo-ocular reflex (VOR) gain with duration of hearing loss and pure tone thresholds for any of the three orthogonal planes. The chisquared test revealed no association between the VOR gain values and the presence or absence of saccades in any of the semicircular canals (p>0.05). Conclusion Huge percentages of individuals with ANSD have been found to have associated vestibular dysfunction as well. Therefore, the vHIT can be used as one of the important tests of the vestibular test battery to evaluate all six semicircular canals in individuals with ANSD.

Very Early (<2 h) Versus Early (12 h) Administration of Caffeine Citrate for Reducing Need for Mechanical Ventilation within 24 h of Life in Preterm Infants on Continuous Positive Airway Pressure

Background: Auditory neuropathy, auditory dys-synchrony, and auditory neuropathy spectrum disorder (ANSD) are variableterms used to describe an auditory disorder seen in patients ranging in age from infants to adults. The prevalence of ANSD indeaf schoolchildren is 2.46% within the age range of 6–12 years. In children, they are detected by the presence of otoacousticemissions (OAEs) in the absence of ABRs. In older age group, difficulty hearing in noise, fluctuating hearing, and speechperception performance not predict ed by the level of residual hearing have been reported. The multitude of etiologies forANSD results in heterogeneous group of patients – making the management strategies even more challenging. The commonetiologies put forward are – prematurity, neonatal insult, genetic abnormality, ototoxic drugs, and head injury.Aim of the Study: This study aims to study the audiological profile in ANSD in a tertiary care hospital and to study the etiologyof ANSD cases.Materials and Methods: A total of 42 patients attending the ENT Outpatient Department of Government Medical College,Kozhikode, with ANSD were included in the study. An ethical committee clearance was obtained before the commencement ofthe study. An ethical committee cleared consent form was used for the study. All ANSD patients were evaluated with a detailedhistory including perinatal and development history, ototoxic drug exposure, head trauma, neurodegenerative conditions, andfamily history. Following clinical evaluation which included general examinations, ENT examination, and central nervous systemexamination, an audiological evaluation, which included pure tone audiometry, speech audiometry, immittance evaluation, OAE,and auditory brainstem response, was done. Radiological investigation (magnetic resonance imaging brain with inner ear – focusingon any structural anomalies; cochlea, vestibulocochlear nerve, and internal auditory canal) was done. Patients were counseledregarding the rehabilitation options based on their audiological and radiological results and the need for follow-up was explained.Observation and Results: A total of 42 patients attending the ENT Outpatient Department (OPD) of Government MedicalCollege, Kozhikode, with ANSD were included in the study. Among the 42 patients, 21 (50%) were in the age group of 11–20 yearsfollowed by 13 patients who were between 0 and 10 years (30.95%). The remaining 8 were aged above 20 years (19.04%).The youngest patient was 10 months old and the oldest was aged 38 years with a mean age of 10.35 ± 2.10 years. Therewere 29 (69.04%) females and 13 (30.95%) males. 3/42 (7.14%) patients gave a history of exposure to ototoxic drugs suchas streptomycin, gentamicin, and kanamycin, but never had a history of loss of hearing before that. History of premature birthwas noted in 10 (23.80%) patients and the remaining patients did not show premature birth history. Among the 42 patients ofthis study group, 23 (54.76%) had low birth weight, of which 2/42 (4.76%) were <1.5 kg. 21/42 (50%) patients had birth weightabove 1.5 kg. 10/42 patients (23.80%) gave a history of neonatal intensive care unit (NICU) admissions at the time of their birth.Conclusions: The major risk factor identified in this study for ANSD was low birth weight with prematurity, NICU admissions,and viral infections having significant contributions. On audiological evaluation, hearing loss was of mild-to-moderate rangewith a low-frequency loss. There was no statistical correlation between pure audiometry values and speech audiometry whichwas a characteristic observation. OAEs were present in the majority of patients with absent cochlear microphonics (reversepolarity) and acoustic reflexes.

The molecular mechanisms underpinning auditory neuropathy / 中华耳鼻咽喉头颈外科杂志

Auditory neuropathy (AN) is a hearing disorder where cochlear inner hair cell and/or the auditory nerve function is disrupted while outer hair cell function is normal. It can affect people of all ages, from infancy to adulthood. People with auditory neuropathy may have normal hearing threshold, or hearing loss ranging from mild to severe; they always have poor speech-perception abilities. It is a heterogeneous disorder which can have either congenital or acquired causes. AN may result from specific loss of cochlear inner hair cells, disordered release of neurotransmitters by inner hair cell ribbon synapses, deafferentation accompanying loss of auditory nerve fibers, neural dys-synchrony or conduction block as a result of demyelination of nerve fibers and auditory nerve hypoplasia. Although the definition of AN includes the central part, its incidence is low, and the etiology and pathology are not clear. The present review aimed to provide an overview of the genetic conditions associated with AN and highlight the neural and synaptic mechanism of AN. Possible strategy for treatments of AN was also discussed.

Retrospective analysis of auditory neuropathy patients after cochlear implantation / 中华耳鼻咽喉头颈外科杂志

Objectives@#To study an effects on hearing ability and speech performance of the patients with auditory neuropathy (AN) after cochlear implantation (CI).@*Methods@#Thirty-five AN patients (26 males and 9 females) after CI in our center since 2007 were chosen, including 5 postlingual patients (implanted age from 14.3 to 38.6 years old) and 30 prelingual patients (implanted age from 1.1 to 13.7 years old). Hearing sensitivity and speech performance were estimated via following methods: (1) implanted hearing thresholds by sound field audiometry; (2) speech audiometry, including monosyllable, disyllable and sentences recognition test by computer-controlled software and sentence recognition test under noise condition (signal to noise ratio=+ 10dB); (3) Mandarin Early Speech Perception test (MESP), Mandarin Pediatric Speech Intelligibility test (MPSI), MAIS, or IT-MAIS for prelingual AN implantees.@*Results@#The average implanted hearing threshold (250-4 000 Hz) was (41.1±11.7) dBHL in 22 AN implantees, while those prelingual implantees was (39.1±10.9) dBHL, and (44.9±12.3) dBHL in postlingual implantees. Speech audiometry were implemented in four of 5 postlingual AN implantees, the results showed increasing tendency in monosyllable recognition scores, dramatic individual variation in computer-controlled disyllable and sentences recognition test, and poor scores (<30%) in speech recognition test in noise condition. Four of 30 prelingual implantees reconstruct their speech recognition ability within 1-3 years after switch-on, characterized as recognition scores (>60%) in monosyllable, disyllable and sentences. The one of prelingual implantee gained recognition scores of speech in noise within 1 year after switch-on. MAIS or IT-MAIS were implemented in twenty-five prelingual implantees, the average score in these patients was 28.6±11.7.@*Conclusion@#Cochlear implant can improve the hearing thresholds of AN patients, however, the improvement in speech performance presented significant variations among the implanted individuals.

Alterações retrococleares na esclerose sistêmica: relato de casos / Retrocochlear impairments in systemic sclerosis: a case report study

RESUMO Objetivo Relatar três casos de pacientes portadores de Esclerose Sistêmica e que apresentaram alterações retrococleares. Método Trata-se de um estudo de relato de casos de três indivíduos com esclerose sistêmica e alteração retrococlear, acompanhados em um serviço de reumatologia. Todos os pacientes realizaram o Potencial Evocado Auditivo de Tronco Encefálico e, quando necessário, nova audiometria. Resultados Todos os indivíduos apresentaram perda auditiva do tipo sensorioneural. Não foi identificado na avaliação audiológica básica qualquer resultado que sugerisse alteração retrococlear, porém o PEATE apresentou-se alterado. Conclusão Pode-se concluir que o estudo revela alterações retrococleares nesta população, ocorrendo tanto nas latências absolutas quanto no intervalo interpico. E, neste contexto, reumatologistas e fonoaudiólogos, ao acompanharem pacientes com esclerose sistêmica, devem estar atentos para a possibilidade da ocorrência dessa alteração nessa população. Revela também, a necessidade de estudos epidemiológicos sobre o tema.

ABSTRACT Purpose To report three cases of patients with Systemic Sclerosis (SSc) and retrocochlear impairments. Methods This is a case report of three individuals with SSc and retrocochlear impairments assisted at a rheumatology outpatient clinic. All individuals underwent Brainstem Auditory Evoked Potential (BAEP) and, when necessary, audiometry. Results All three individuals presented sensorineural hearing loss. Although no retrocochlear impairment was identified in the basic audiologic evaluation, the BAEP results were altered. Conclusion Retrocochlear impairments were present in the individuals under study, both in the absolute latencies and interpeak interval, thereby demanding the attention of rheumatologists and speech-language pathologists to such changes during the monitoring of SSc patients. The results also show a need for epidemiological studies on the theme.

A Case of Auditory Neuropathy Caused by Pontine Hemorrhage in an Adult

A pontine hemorrhage can evoke several neurological symptoms because the pons contains various nuclei and nerve fibers. Hearing loss can develop as a result of a pontine hemorrhage because there is an auditory conduction pathway in the cochlear nucleus of the pons. However, very few cases of hearing loss caused by pontine lesions have been reported, and there have been no reports of auditory neuropathy that developed following a pontine hemorrhage. Recently we had a patient who experienced a nontraumatic pontine hemorrhage who was diagnosed with auditory neuropathy. The 34-year-old male patient was admitted to the emergency department with sudden alteration of mental status. His brain computed tomographic imaging revealed a hemorrhage in the central pons. He complained of hearing difficulties after his mental status recovered through conservative treatment, but a pure-tone audiogram showed very mild hearing loss in both ears. Further hearing tests using otoacoustic emissions, which showed normal responses, and auditory brainstem responses, which showed no waveforms at maximum stimulus intensity, revealed that his hearing difficulties were caused by auditory neuropathy. This case implies that the threshold of sound detection can be preserved in patients with pontine hemorrhage who complain of hearing difficulties. Auditory neuropathy should be considered as a possible cause of hearing difficulties in these patients and appropriate hearing tests should be performed.

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.

Audiological Profile of Adult Persons with Auditory Neuropathy Spectrum Disorders

BACKGROUND AND OBJECTIVES: The auditory profile of a large number of persons with late onset auditory neuropathy spectrum disorder (ANSD) is recently described in the Indian context. The purpose of study was 1) to profile data on routine audiological parameters, cortical evoked potentials, and temporal processing, 2) to analyze the benefit from hearing aids for persons with ANSD, and 3) to understand the association between benefit from hearing aids and auditory profile. SUBJECTS AND METHODS: Thirty-eight adults with late onset ANSD and a matched group of 40 normally hearing adults participated in the study. Basic audiological tests, recording of cortical evoked potentials, and temporal processing tests were carried out on both groups of participant while only persons with ANSD were fitted with hearing aid. RESULTS: Subjects in the two groups were significantly different on all the audiological parameters. ANSD group seemed to benefit from hearing aids variably. The mean amplitude of N2 was significantly different between normally-hearing participants and patients with ANSD. CONCLUSIONS: Residual temporal processing, particularly amplitude modulation detection seems to be associated with benefit from hearing aids in patients with ANSD.

Auditory Brainstem Response Improvements in Hyperbillirubinemic Infants

BACKGROUND AND OBJECTIVES: Hyperbillirubinemia in infants have been associated with neuronal damage including in the auditory system. Some researchers have suggested that the bilirubin-induced auditory neuronal damages may be temporary and reversible. This study was aimed at investigating the auditory neuropathy and reversibility of auditory abnormalities in hyperbillirubinemic infants. SUBJECTS AND METHODS: The study participants included 41 full term hyperbilirubinemic infants (mean age 39.24 days) with normal birth weight (3,200-3,700 grams) that admitted in hospital for hyperbillirubinemia and 39 normal infants (mean age 35.54 days) without any hyperbillirubinemia or other hearing loss risk factors for ruling out maturational changes. All infants in hyperbilirubinemic group had serum bilirubin level more than 20 milligram per deciliter and undergone one blood exchange transfusion. Hearing evaluation for each infant was conducted twice: the first one after hyperbilirubinemia treatment and before leaving hospital and the second one three months after the first hearing evaluation. Hearing evaluations included transient evoked otoacoustic emission (TEOAE) screening and auditory brainstem response (ABR) threshold tracing. RESULTS: The TEOAE and ABR results of control group and TEOAE results of the hyperbilirubinemic group did not change significantly from the first to the second evaluation. However, the ABR results of the hyperbilirubinemic group improved significantly from the first to the second assessment (p=0.025). CONCLUSIONS: The results suggest that the bilirubin induced auditory neuronal damage can be reversible over time so we suggest that infants with hyperbilirubinemia who fail the first hearing tests should be reevaluated after 3 months of treatment.

Auditory Neuropathy/Dyssynchrony in Biotinidase Deficiency

Biotinidase deficiency is a disorder inherited autosomal recessively showing evidence of hearing loss and optic atrophy in addition to seizures, hypotonia, and ataxia. In the present study, a 2-year-old boy with Biotinidase deficiency is presented in which clinical symptoms have been reported with auditory neuropathy/auditory dyssynchrony (AN/AD). In this case, transient-evoked otoacoustic emissions showed bilaterally normal responses representing normal function of outer hair cells. In contrast, acoustic reflex test showed absent reflexes bilaterally, and visual reinforcement audiometry and auditory brainstem responses indicated severe to profound hearing loss in both ears. These results suggest AN/AD in patients with Biotinidase deficiency.

Auditory Neuropathy/Dyssynchrony: A Retrospective Analysis of 15 Cases

Introduction Auditory neuropathy/dyssynchrony (AN/AD) comprises a spectrum of pathology affecting the auditory pathways anywhere from the inner hair cells to the brainstem. It is characterized by an absent or atypical auditory brainstem response (ABR) with preservation of the cochlear microphonics and/or otoacoustic emissions (OAEs). Objective Retrospective analysis of patients with AN/AD. Methods Fifteen patients with AN/AD were included in this study and their records were retrospectively investigated. Results Possible etiology of AN/AD was neonatal hyperbilirubinemia in three patients, family history of hearing loss in three patients, consanguineous marriage in two patients, head trauma in two patients, mental motor retardation in one patient, cerebrovascular disease in one patient, and there was no apparent cause in three patients. Conclusion Otolaryngologists should keep in mind the diagnosis of AN/AD especially in patients complaining of difficulty in hearing and speech and audiological evidence of disassociation between pure tone and speech audiometry. ABR and OAE testing is recommended in these patients for AN/AD diagnosis. .

Role of Cochlear Microphonic in Newborn Hearing Test / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Cochlear microphonic (CM) is an electrical potential generated by outer hair cells in response to acoustic stimulation. The aim of this study is to evaluate the significance of CM in neonatal hearing loss. SUBJECTS AND METHOD: From April 2013 to April 2014, 64 neonates hospitalized in neonatal intensive care unit were enrolled. Subjects underwent transient evoked otoacoustic emission (TEOAE), auditory brain stem response (ABR) and CM. We analyzed the results of hearing tests and the correlation between CM and the other test modalities. RESULTS: Ninety two ears showed normal ABR waves whereas the other 36 ears had abnormal ABR. There were two neonates who were suspected of auditory neuropathy because of the presence of TEOAE and CM. Among 14 ears who showed abnormal OAE results, 12 ears (86%) were identified as having CM. The amplitudes of CMs were correlated with the reproducibility of TEOAE (p<0.005). Between the ears with positive TEOAE and others with negative TEOAE, the amplitudes of CMs were significantly different (p<0.005). CONCLUSION: Many ears were identified with the presence of CM without TEOAE response because of the the vulnerability of OAE from middle ear status and environment. We suppose that CM might provide information on outer hair cell function to complement the OAE in neonatal hearing test.

The Ability of Temporal Gap Detection in Listeners with Auditory Neuropathy Spectrum Disorder / 听力学及言语疾病杂志

Objective This study was aimed at investigating the ability of temporal gap detection (TGD) in listeners with auditory neuropathy spectrum disorder (ANSD ) .Methods The temporal gap detection thresholds were measured for subjects using a TGD program developed by University of California ,Irvine .Three groups of subjects were recruited in this study ,including 12 subjects with normal hearing ,12 subjects with sensorineural hearing loss (SNHL) ,and 15 subjects with ANSD .The differences of TGD thresholds among the three groups of subjects were analyzed using a one - sample ANOVA method .Results No significant difference of the TGD thresh‐old was observed between two ears for all the subjects .The mean and standard deviation of the gap - detection threshold for both ears was about 3 .9 ± 1 .1 ms ,3 .6 ± 1 .1 ms ,and 13 .7 ± 9 .9 ms for normal - hearing subjects , subjects with SNHL ,and subjects with ANSD ,respectively .The TGD threshold in subjects with ANSD was sig‐nificantly higher than those of in normal hearing group (P< 0 .01) and SNHL group (P< 0 .01) ,while no signifi‐cant difference was found in TGD thresholds between normal - hearing subjects and subjects with SNHL .Conclusion For listeners with auditory neuropathy spectrum disorder ,their ability to resolve temporal information was de‐graded with a large individual variability .

Damage of Spiral Ganglion Cell Induced by Ouabain Application in Cat / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Auditory neuropathy is a hearing disorder characterized by the absence or the marked impairment of the auditory brainstem responses with the preservation of the cochlear microphonics (CMs) and otoacoustic emissions. This suggests that outer hair cell (OHC) function is normal but proximal auditory function to OHCs is impaired. It is assumed that the lesion is localized at the level of the inner hair cells (IHCs), auditory nerve fibers, or the synapse between them. This study was aimed to observe the change of hearing threshold and pathology of spiral ganglion cell induced by ouabain application, and present basic data to explain the auditory neuropathy. MATERIALS AND METHOD: Twenty ears of twenty normal hearing cats were used in this study. Cats were treated with 100 microL ouabain (1 mM) applied on the round window. After three days, compound action potential (CAP) and CM were measured and the cochlea was obtained. Pathologic change of spiral ganglion cell was evaluated under light microscope after H&E stain. Normal saline was injected for the control group. RESULTS: In the ouabain group, CAP threshold was increased in all tested frequencies (p0.05). There was significant difference between CAP and CM threshold shift (p<0.001). In the control group, there was no significant difference in CAP and CM thresholds. Light microscopic findings show that the condensed chromatin and nuclear fragments of spiral ganglion cells of an ear was exposed to ouabain, and outer hair cell and inner hair cell were not damaged. CONCLUSION: This study shows that the CAP threshold was significantly increased but the CM threshold was not changed in the ouabain group. Ouabain induced damage of spiral ganglion cells. This study is not sufficient to explain auditory neuropathy because threshold shift of CAP is not obvious, but it would be helpful to explain that selective damage of spiral ganglion cell would be the mechanism of auditory neuropathy.

A Case of Auditory Neuropathy with Recovery of Normal Hearing

Newborn hearing screening test is very important in the early diagnosis of childhood hearing loss because it affects language development. Auditory neuropathy is a spectrum disorder characterized by abnormal auditory brainstem response but preserved otoacoustic emission and cochlear microphonics. In general, auditory neuropathy patients have poor word discrimination and variable patterns of pure tone audiometry. We report on a patient with auditory neuropathy diagnosed at 16 months of age and started wearing hearing aids, but showed normal pure tone and speech audiometric findings 3 years later. Close follow-up for patients with auditory neuropathy is recommended.

O espectro da neuropatia auditiva pode contribuir para acidente de trabalho? o relato de uma investigação clínica / Can auditory neuropathy spectrum disorder contribute to work accidents? a clinical investigation report

Considerando a possível insuficiência do exame admissional legalmente preconizado para avaliação auditiva no que se refere à identificação de comprometimento da habilidade para reconhecer fala em ambiente ruidoso, este trabalho tem como objetivo relatar o processo de uma investigação clínica, conduzida em 2010, de um trabalhador que sofreu acidente de trabalho, visando identificar possíveis elementos clínicos não previamente considerados, mas que poderiam ter contribuído para a ocorrência do acidente. Utilizou-se a escala Abbreviated Profile of Hearing Aid Benefit para comparar a habilidade de reconhecimento da fala em ambiente ruidoso do trabalhador acidentado com a de ouvintes normais e realizaram-se exames de audiometria, imitanciometria, emissões otoacústicas, potencial evocado auditivo de tronco encefálico e teste de reconhecimento de sentenças no silêncio e no ruído. Identificou-se que o trabalhador apresentava espectro da neuropatia auditiva (ENA) e que a alteração neural prejudicava de forma relevante a compreensão da fala em presença de ruído. A avaliação da sensibilidade auditiva no exame admissional se mostrou insuficiente para identificar a real situação auditiva do trabalhador com ENA, que compromete o reconhecimento de sinais de advertência, levando a um aumento no risco de ocorrência de acidente em ambientes ruidosos.

Considering that the hearing assessment test legally recommended for job admission exams is not adequate to identify impaired ability to recognize speech in noisy environments, this paper reports a clinical investigation conducted in 2010 for a worker who suffered a work accident due to noise. It aimed at identifying clinical elements which were not previously taken into consideration, but that could have contributed to the accident. Abbreviated Profile of Hearing Aid Benefit Scale was used to measure the injured worker's ability to recognize speech in a noisy environment and to compare it with the hearing skill of normal adults. Audiometry, tympanometry, otoacoustic emissions, auditory evoked brainstem potential, and sentence recognition in quiet and in noisy environments were also carried out. They showed that the worker had an Auditory Neuropathy Spectrum Disorder (ANSD) and that the neural disorder significantly impaired speech understanding in noisy surroundings. Hearing sensitivity assessment during job admission exams was not enough to identify the actual hearing ability of the worker with ANSD, as the disorder prevents warning signs from being noticed and increases risk of accidents in noisy environments.

Perfil pragmático longitudinal de uma criança no espectro da neuropatia auditiva / Longitudinal pragmatic profile of a child with auditory neuropathy spectrum disorder

A maior parte da comunicação humana depende da conversão de ideias em linguagem, envolvendo a interação de todos os seus componentes - fonológico, semântico, sintático e pragmático. A pragmática estuda a relação entre o significado social da linguagem e seu conteúdo semântico, manifestado pelo ato comunicativo em si. O espectro da neuropatia auditiva gera uma dessincronia na condução nervosa, contribuindo para o prejuízo na percepção da fala. Na criança deficiente auditiva, o processo de aquisição e desenvolvimento da linguagem pode ser estimulado com a intervenção. O objetivo dessa pesquisa foi realizar acompanhamento longitudinal do uso das habilidades pragmáticas de comunicação por uma criança com espectro da neuropatia auditiva. A criança realizou intervenção fonoaudiológica por três anos na área de Audiologia Educacional. Foram gravadas conversações espontâneas, ao início de cada ano, transcritas e analisadas segundo protocolo de habilidades comunicativas verbais. Na gravação inicial, a criança apresentou maior número de habilidade de respostas diretas; porém, estas foram ampliadas com o fornecimento de respostas mais complexas ao longo da intervenção. Na última gravação, já propõe novos tópicos de discurso, realiza narrativas e argumentações. O surgimento de habilidades comunicativas refinadas é explicado pelo desenvolvimento da linguagem, que é potencializado pela terapia com deficientes auditivos. Pode-se concluir que para o caso apresentado a intervenção fonoaudiológica proporcionou melhora nas habilidades pragmáticas de comunicação.

Human communication depends mostly on the conversion of ideas into language, involving the interaction among all its components - phonological, semantic, syntactic and pragmatic. Pragmatics studies the relationship between the social meaning of language and its semantic content, expressed by the communicative act itself. Auditory neuropathy spectrum disorder generates a dyssynchrony in nerve conduction, contributing to an impairment in speech perception. In hearing impaired children the language acquisition and development process can be stimulated with intervention. The aim of this study was to present a longitudinal follow-up of the use of pragmatic communication abilities by a child with auditory neuropathy spectrum disorder. The child received speech-language pathology therapy during three years in the Educational Audiology area. Video recordings of spontaneous conversation were made in the beginning of each year. These recordings were transcribed and analyzed according to the verbal communicative abilities protocol. In the initial recording, the most frequent ability presented by the child was the direct response; however these were extended to more complex responses during the intervention. In the last recording the child proposes new topics of discourse, produce narratives and arguments. The emergence of more sophisticated communication skills is justified by the language development, which benefits from language therapy with hearing impaired children. This suggests that, for the case study described, speech-language pathology therapy contributed to the improvement of pragmatic communication abilities.