Auditory Neuropathy/Auditory Synaptopathy.

Patients with auditory neuropathy (AN)/auditory synaptopathy (AS) present unique evaluation and management challenges. Communication ability using auditory stimuli varies among patients, with particular difficulty understanding speech in noise. Auditory physiologic responses are key to accurate identification and monitoring of patients with AN/AS. Management approaches should consider individual variation and the possibility of change over time. Many patients with accurately characterized AN/AS demonstrate success with cochlear implants. Areas of discovery, including understanding of synaptic and neural mechanisms, genotype/phenotype relationships, and use of cochlear and cortical evoked potentials, will promote accurate clinical evaluation and management of infants, children, and adults with AN/AS.

An integrative approach for pediatric auditory neuropathy spectrum disorders: revisiting etiologies and exploring the prognostic utility of auditory steady-state response.

Auditory neuropathy is an important entity in childhood sensorineural hearing loss. Due to diverse etiologies and clinical features, the management is often challenging. This study used an integrative patient-history, audiologic, genetic, and imaging-based approach to investigate the etiologies and audiologic features of 101 children with auditory neuropathy. Etiologically, 48 (47.5%), 16 (15.8%), 11 (10.9%), and 26 (25.7%) children were categorized as having acquired, genetic, cochlear nerve deficiency-related, and indefinite auditory neuropathy, respectively. The most common causes of acquired and genetic auditory neuropathy were prematurity and OTOF mutations, respectively. Patients with acquired auditory neuropathy presented hearing loss earlier (odds ratio, 10.2; 95% confidence interval, 2.2-47.4), whereas patients with genetic auditory neuropathy had higher presence rate of distortion product otoacoustic emissions (odds ratio, 10.7; 95% confidence interval, 1.3-85.4). In patients with different etiologies or pathological sites, moderate to strong correlations (Pearson's r = 0.51-0.83) were observed between behavioral thresholds and auditory steady-state response thresholds. In conclusion, comprehensive assessments can provide etiological clues in ~75% of the children with auditory neuropathy. Different etiologies are associated with different audiologic features, and auditory steady-state responses might serve as an objective measure for estimating behavioral thresholds.

Relationship research between auditory neuropathy spectrum disorder and exchange transfusion in neonates with severe hyperbilirubinemia.

OBJECTIVE: To explore the effects of exchange transfusion on auditory neuropathy spectrum disorder (ANSD) in neonates with severe hyperbilirubinemia (SH). METHODS: The clinical data of 2216 SH neonates who met the standard of exchange transfusion and 732 non severe-hyperbilirubinemia (NSH) neonates in the same period who did not require exchange transfusion in the neonatology department of Childrens' Hospital of Chongqing Medical University between January 2010 and December 2015 were retrospectively analyzed. In addition, the SH neonates were further divided into the exchange transfusion group and photography group. Hearing screening was conducted on all neonates using transiently evoked otoacoustic emission (TEOAE) and auto auditory brainstem response (AABR), and neonates who failed the above screening were performed diagnostic hearing test. And then neonates diagnosed with hearing disorder were followed up for 2-5 years. RESULTS: The pass rates of hearing screening were 80.58%, 79.71% and 87.84% in the phototherapy group, exchange transfusion group and NSH group respectively, with a significant difference(P < 0.05). Hearing loss was diagnosed in 10.15%, 12.39% and 8.54% of neonates in the phototherapy group, exchange transfusion group and NSH group. After follow-up, ultimate incidence rates of ANSD were 11.96%, 11.57% and 2.4% respectively in the 3 groups, with a significant difference (P < 0.05). CONCLUSIONS: SH is one of risk factors for ANSD. SH neonates have a lower incidence of ANSD in the exchange transfusion group than in the phototherapy group. Neonates who meet the standards of exchange transfusion adopt this therapy in early stage, which can quickly decrease bilirubin level and ultimately reduce incidence of ANSD.

Effectiveness of low-cut modified amplification strategy and channel-free hearing aid in individuals with auditory neuropathy spectrum disorder.

OBJECTIVE: The present study attempted to compare the aided benefit using low-cut modified amplification and channel-free hearing aids in individuals with auditory neuropathy spectrum disorder (ANSD). It was also attempted to determine these effects in good and poor performers with ANSD. DESIGN: Cross-sectional within group pretest, post-test design. STUDY SAMPLE: Twenty-five individuals with acquired ANSD were selected for the study. The study sample included 11 males and 14 females between the age ranges of 17-40 years (mean age of 24.6 years). RESULTS: The results of the repeated measures analysis of variance (ANOVA) showed that aided benefit was significantly higher with the channel-free hearing aid. Mixed ANOVA results showed that the improvement was more in good performers than poor performers with ANSD. Multiple regression analyses showed that speech identification scores are a strong predictor of aided benefit. CONCLUSIONS: The results of the present study suggest that channel-free hearing aids and low-cut modified amplification can be used as an efficient alternative technique during hearing aid fitting for individuals with ANSD. However, further evidence-based studies on a larger group are essential to validate the results.

Cortical development and neuroplasticity in Auditory Neuropathy Spectrum Disorder.

Cortical development is dependent to a large extent on stimulus-driven input. Auditory Neuropathy Spectrum Disorder (ANSD) is a recently described form of hearing impairment where neural dys-synchrony is the predominant characteristic. Children with ANSD provide a unique platform to examine the effects of asynchronous and degraded afferent stimulation on cortical auditory neuroplasticity and behavioral processing of sound. In this review, we describe patterns of auditory cortical maturation in children with ANSD. The disruption of cortical maturation that leads to these various patterns includes high levels of intra-individual cortical variability and deficits in cortical phase synchronization of oscillatory neural responses. These neurodevelopmental changes, which are constrained by sensitive periods for central auditory maturation, are correlated with behavioral outcomes for children with ANSD. Overall, we hypothesize that patterns of cortical development in children with ANSD appear to be markers of the severity of the underlying neural dys-synchrony, providing prognostic indicators of success of clinical intervention with amplification and/or electrical stimulation. This article is part of a Special Issue entitled .

Auditory neuropathy.

Neural disorders of the auditory nerve are associated with particular disorders of auditory perceptions dependent on processing of acoustic temporal cues. These include: (1) speech perception; (2) localizing a sound's origin in space; and (3) identifying sounds in background noise. Auditory neuropathy (AN) is a consequence of: (1) presynaptic disorders affecting inner hair cell ribbon synapses; (2) postsynaptic disorders of auditory nerve dendrites; and (3) postsynaptic disorders of auditory nerve axons. The etiologies of these disorders are diverse, similar to other cranial or peripheral neuropathies. The pathologies cause attenuated and dyssynchronous auditory nerve discharges. Therapies and management of patients with AN are reviewed.

Electrocochleography in children with auditory synaptopathy/neuropathy: diagnostic findings and characteristic parameters.

INTRODUCTION: The early diagnosis of AS/AN in children remains challenging because it exclusively relies on the detection of OAE and/or CM, while ABR are pathologically changed or missing. The aim of our study was to ensure the diagnosis of AS/AN, demarcate it to an outer hair cell damage and possibly differentiate between pre- and postsynaptic pathologies. METHODS: We retrospectively evaluated the transtympanic ECochG results of ten children with AS/AN and compared them to a matched group with SNHL and without any signs of AS/AN. We analyzed the thresholds, latencies and - as a new parameter - the amplitude ratio between CAP and SP. RESULTS: CM and SP thresholds were significantly lower than CAP thresholds in AS/AN patients and significantly lower than SP and CM thresholds in SNHL patients with comparable CAP thresholds. The CAP/SP ratio of amplitudes in SNHL children was more than three times (significantly) higher than in AS/AN children. The cutoff value was set at 1.0 in order to differentiate between both groups with a 80-90% sensitivity and specificity. It was not possible to differentiate between a pre- and postsynaptic type of AS/AN in our collective. SUMMARY AND CONCLUSION: The ECochG can add valuable information for a precise differential diagnosis of AS/AN, especially in babyhood. We identified the CAP/SP ratio as a new parameter for differentiation between AS/AN and SNHL. When the CAP/SP ratio falls below 1.0, patients can be diagnosed AS/AN with high specificity and sensitivity. Significantly smaller SPL are needed to evoke SP and CM in the AS/AN group, thus showing the preserved hair cell function.

Auditory neuropathy in late preterm infants treated with phototherapy for hyperbilirubinemia.

OBJECTIVE: To evaluate the prevalence of auditory neuropathy (AN) in late preterms treated with phototherapy for hyperbilirubinemia. DESIGN: Prospective observational study comprising late preterms treated with phototherapy for hyperbilirubinemia. Newborns were screened with combined transient-evoked otoacoustic emissions (TEOAEs) / automated auditory brainstem responses (AABR). Infants who failed screening underwent diagnostic (ABR). Infants were all re-evaluated with AABR at one year. STUDY SAMPLE: Eighty-five infants with a mean serum total bilirubin concentration of 22.3 ± 1.76 mg/dl; severe-hyperbilirubinemia (SH), and 102 infants with a mean serum total bilirubin concentration of 18.6 ± 1.26 mg/dl; non-severe hyperbilirubinemia (NSH) were included. RESULTS: From 85 late preterms with SH, six (7.1%) failed screening and underwent diagnostic ABR for six weeks. AN was diagnosed in two (2%) infants with SH. Four (3.9%) of the 102 controls with NSH demonstrated failure at TEOAE/AABR. No AN was diagnosed in the control group at the diagnostic ABR. No statistically significant difference was found between infants treated with phototherapy for SH and NSH with regard to AN/AD either in the postnatal period or at one year. No correlation was found between serum bilirubin levels and ABR latencies or thresholds. CONCLUSIONS: AN (2%) in late preterms treated with phototherapy for severe-hyperbilirubinemia was not higher than in those with non-severe hyperbilirubinemia.

Auditory neuropathy in individuals with Type 1 diabetes.

Peripheral neuropathy is a major consequence of diabetes mellitus with up to 50 % of patients showing clinically significant neural injury during the disease course. Hearing loss (as defined by impaired sound detection thresholds) is a recognized symptom of DM, but the possibility of auditory neuropathy (AN) has not been explored in this population. This pilot study investigated peripheral auditory function, auditory processing and speech perception in individuals with Type 1 diabetes mellitus (T1DM) and compared the findings with measures of vestibular function, ocular pathology/visual acuity and overall neurologic profile. Ten adults with T1DM and ten matched controls underwent a battery of tests which included: audiometry, otoacoustic emissions, auditory brainstem responses, temporal processing measures and speech perception. Six of the ten T1DM participants showed electrophysiologic evidence of AN and impaired functional hearing. Furthermore, auditory capacity was correlated with both visual acuity and degree of somatic peripheral neuropathy. This pilot investigation revealed functional-hearing deficits severe enough to impact upon everyday communication. Should the findings be confirmed by larger studies, auditory evaluation may form an important part of the management regimen for individuals with T1DM. This may be especially important for those with DM-related eye conditions, as deficits across multiple sensory modalities can have multiplicative detrimental effects on quality-of-life.

Time-frequency analysis of transient evoked-otoacoustic emissions in individuals with auditory neuropathy spectrum disorder.

The aim of the study was to describe and quantify the cochlear active mechanisms in individuals with Auditory Neuropathy Spectrum Disorders (ANSD). Transient Evoked Otoacoustic Emissions (TEOAEs) were recorded in 15 individuals with ANSD and 22 individuals with normal hearing. TEOAEs were analyzed by Wavelet transform method to describe and quantify the characteristics of TEOAEs in narrow-band frequency regions. It was noted that the amplitude of TEOAEs was higher and latency slightly shorter in individuals with ANSD compared to normal hearing individuals at low and mid frequencies. The increased amplitude and reduced latencies of TEOAEs in ANSD group could be attributed to the efferent system damage, especially at low and mid frequencies seen in individuals with ANSD. Thus, wavelet analysis of TEOAEs proves to be another important tool to understand the patho-physiology in individuals with ANSD.

Effect of companding on speech recognition in quiet and noise for listeners with ANSD.

OBJECTIVE: The present study assesses the effect of companding on speech perception in quiet and noise for listeners with auditory neuropathy spectrum disorder (ANSD). DESIGN: Speech perception was assessed using speech reception threshold in noise (SRTn) for sentences and consonant identification in quiet and at different signal-to-noise ratios (15, 10, 5, and 0 dB SNR). STUDY SAMPLE: Ten ANSD listeners and normal-hearing listeners participated in the study. RESULTS: ANSD listeners required significantly higher SRTn when compared to the normal-hearing listeners. Companding reduced SRTn more significantly in listeners with ANSD, but for normal-hearing listeners there was only a marginal reduction. In the consonant identification task, ANSD listeners performed poorer than normal-hearing listeners in quiet and noise. Companding improved consonant identification in quiet and at 15 dB SNR for listeners with ANSD, whereas no improvement was observed in normal-hearing listeners. CONCLUSION: Results of the present study demonstrate that companding improved speech perception in quiet and noise for ANSD listeners. The amount of improvement is higher at higher SNRs. In normal-hearing listeners, companding showed marginal improvement in both quiet and noise. The findings are discussed for rehabilitation of ANSD listeners by hearing aids which incorporate the companding strategy.

Masking effects in patients with auditory neuropathy-possible involvement of suppression mechanism caused by normal outer hair cell function.

OBJECTIVE: Variations in the effects of masking noise were evaluated in different pathologies of sensorineural hearing loss. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Fifty-five ears of 30 patients with sensorineural hearing loss who underwent noise audiometry in the Department of Otolaryngology-Head and Neck Surgery, Tohoku University Hospital, since 2010, because of complaints of hearing difficulty in noisy environments. MAIN OUTCOME MEASURES: Masked threshold for narrow band and white noise. RESULTS AND DISCUSSION: Masking effects in patients with auditory neuropathy were significantly larger than those in patients with other types of hearing losses. Masking effects of broad band white noise were greater than those of narrow band noise. Masking effects could be observed for white noise even in the elevated unmasked threshold region, where little contribution of excitatory masking effect would be expected. The present findings support the idea that the suppression mechanism caused by normal outer hair cell function is important in the masking phenomenon in patients with auditory neuropathy.

Spatial hearing in a child with auditory neuropathy spectrum disorder and bilateral cochlear implants.

OBJECTIVE: The neural dys-synchrony associated with auditory neuropathy spectrum disorder (ANSD) causes a temporal impairment that could degrade spatial hearing, particularly sound localization accuracy (SLA) and spatial release from masking (SRM). Unilateral cochlear implantation has become an accepted treatment for ANSD but treatment options for the contralateral ear remain controversial. We report spatial hearing measures in a child with ANSD before and after receiving a second cochlear implant (CI). STUDY SAMPLE: An 11-year-7-month old boy with ANSD and expressive and receptive language delay received a second CI eight years after his first implant. DESIGN: The SLA and SRM were measured four months before sequential bilateral CIs (with the contralateral ear plugged and unplugged), and after nine months using both CIs. RESULTS: Testing done before the second CI, with the first CI alone, suggested that residual hearing in the contralateral ear contributed to sound localization accuracy, but not word recognition in quiet or noise. Nine-months after receiving a second CI, SLA improved by 12.76° and SRM increased to 3.8-4.2 dB relative to pre-operative performance. Results were compared to published outcomes for children with bilateral CIs. CONCLUSIONS: The addition of a second CI in this child with ANSD improved spatial hearing.

Auditory system dysfunction due to infantile thiamine deficiency: long-term auditory sequelae.

Eleven infants who were fed a thiamine-deficient formula for a mean of 3 months were evaluated for immediate and long-term auditory abnormalities. At presentation, 8 infants had auditory neuropathy spectrum disorder (ANSD), which resolved with supplementary thiamine in 5 children, was permanent in 2 children, and deteriorated in 1 patient who died at the age of 7 years. An additional patient had an auditory pattern corresponding to that of auditory neuropathy of brain stem origin. The 2 remaining patients had unilateral cochlear hearing loss. Six to 8 years later, all patients with transient ANSD had normal audiograms, 2 patients had unilateral cochlear hearing loss, and the rest had neural hearing loss. All survivors had a language developmental delay and impaired speech intelligibility of varying degrees, especially in the presence of background noise. Thiamine is crucial for normal auditory development and function, and its deficiency may be considered an acquired metabolic cause of ANSD in infants.

Hearing status in neonatal hyperbilirubinemia by auditory brain stem evoked response and transient evoked otoacoustic emission.

Hyperbilirubinemia at neonatal period is one of the major deteriorating factors of the auditory system. If left untreated, it may cause certain cerebral damage. This study aims to evaluate the impact of hyperbilirubinemia on the hearing of neonate. This study was conducted on 35 newborn babies with jaundice (bilirubin more than 20 mg/dL). Auditory brainstem response (ABR) and transient evoked otoacoustic emission (TEOAE) tests were performed, after treatment and one year after. ABR test results indicated that 26 children (74.3%) had normal hearing but 9 (25.7%) suffered from an impairment. As for TEOAE test, 30 children (85.7%) passed whereas the remaining (14.3%) seemed to be failures. The comparative results of the two tests pointed to autonomic neuropathy /autonomic dysreflexia symptoms in 5 babies. Due to the high incidence of autonomic neuropathy/autonomic dysreflexia among hyperbilirubinemic babies, screening in this regard seems reasonable. Our result emphasizes the necessity of more experiments on the afflicted areas.

Estudio electrofisiológico y electroacústico de un desorden del espectro de neuropatía auditiva: reporte de un caso en recién nacido de alto riesgo / Electrophysiology and electroacoustic study of spectrum disorder of auditory neuropathy: report of a case in high-risk newborn

El desorden del espectro de neuropatía auditiva (DENA) describe una condición en la cual se observa o se ha observado emisiones otoacústicas (EOA) junto con potenciales evocados auditivos de tronco (PEAT) anormales o ausentes. Su identificación se basa en la presencia de potencial microfónico coclear (PMIC) junto con un PEAT anormal o ausente y EOA presentes o antecedentes de su presencia. Los umbrales tonales pueden encontrarse entre los rangos de normalidad hasta pérdidas auditivas profundas. El reconocimiento del habla generalmente se encuentra afectado particularmente en presencia de ruido de fondo, sin embargo en algunos individuos se mantiene conservado (sin ruido). Se presenta caso clínico de un recién nacido de sexo femenino de pretérmino de 29 semanas y 810 grs (GIII), apgar 7/8, presenta displasia broncopulmonar, sospecha de infección connatal tratada, hiperbilirrubinemia (max 11 mg/dl) tratada con fototerapia. Es derivada al Servicio de Otorrinolaringología para su evaluación auditiva. La evaluación auditiva realizada corresponde a potenciales evocados auditivos de tronco (PEAT), impedanciometria, audiometría de campo de respuesta reflejas y emisiones oto-acústicas. Los resultados obtenidos concuerdan con lo descrito en la literatura para un DENA.

Auditory neuropathy spectrum disorder (ANSD) describes a condition in which it is possible to find otoacoustic emissions (OAE) in presence of abnormal or absent auditory brainstem evoked potentials (ABR). The pure tone thresholds may show a spectrum from normal to profound hearing loss. Speech recognition is often affected in presence of background noise, but in some individuals remains intact. We report a case of a pre term newborn (female) of 29 weeks and 810 grams, Apgar 7/8, bronchopulmonary dysplasia, suspected connatal infection, and hyperbilirubinemia (max 11 mg / dl). She was referred to Hospital Padre Hurtado for hearing assessment. The hearing test performed were an ABR, tympanometry & acoustic reflex, visual reinforcement audiometry and otoacoustic emissions. The results are consistent with those described in the literature for ANSD.

Risk factors for auditory neuropathy spectrum disorder in NICU infants compared to normal-hearing NICU controls.

OBJECTIVES: To evaluate independent etiologic factors associated with auditory neuropathy spectrum disorder (ANSD) in infants who have been admitted to the neonatal intensive care unit (NICU) compared to normal-hearing controls. STUDY DESIGN: Case-control study. METHODS: We included all infants (n = 9) with the ANSD profile admitted to the NICU of Sophia Children's Hospital between 2004 and 2009. Each patient was matched with four normal-hearing controls of the same gender and postconceptional age. The following possible risk factors were studied: birth weight, dysmorphic features, APGAR scores (at 1, 5, and 10 minutes), respiratory distress (IRDS), cytomegalovirus (CMV) infection, sepsis, meningitis, cerebral bleeding, hyperbilirubinemia requiring phototherapy, peak total bilirubin level, furosemide, dexamethason, vancomycin, gentamycin, and tobramycin administration. RESULTS: Nine infants met the ANSD criteria in one or both ears. IRDS (P = .02), meningitis (P = .04), and vancomycin administration (P = .009) were significantly increased in infants with ANSD compared to controls. CONCLUSIONS: In high-risk NICU infants IRDS, meningitis and vancomycin administration are associated with auditory neuropathy spectrum disorder.

Auditory steady state response in auditory neuropathy.

REVIEW: Auditory neuropathy is a disorder characterised by preservation of outer hair cell function, with normal otoacoustic emissions and/or cochlear microphonics, but an absent or distorted auditory brainstem response. PURPOSE: This study aimed to objectively assess hearing thresholds in patients with auditory neuropathy, using the auditory steady state response. MATERIALS AND METHODS: Thirteen patients with auditory neuropathy and 15 normal hearing subjects were examined. Audiological evaluation included basic audiological tests, otoacoustic emissions, auditory brainstem response and auditory steady state response. RESULTS: In the auditory neuropathy patients, the auditory brainstem response was absent in 11 patients, while the auditory steady state response was absent in only three. CONCLUSION: The auditory steady state response may serve as a valuable objective measure for assessing the hearing threshold across different frequencies in patients with auditory neuropathy. We recommend that auditory steady state response be used to complete the evaluation of patients with auditory neuropathy.

An electrophysiological measure of binaural hearing in noise.

BACKGROUND: A common complaint of patients with (central) auditory processing disorder is difficulty understanding speech in noise. Because binaural hearing improves speech understanding in compromised listening situations, quantifying this ability in different levels of noise may yield a measure with high clinical utility. PURPOSE: To examine binaural enhancement (BE) and binaural interaction (BI) in different levels of noise for the auditory brainstem response (ABR) and middle latency response (MLR) in a normal hearing population. RESEARCH DESIGN: An experimental study in which subjects were exposed to a repeated measures design. STUDY SAMPLE: Fifteen normal hearing female adults served as subjects. Normal hearing was assessed by pure-tone audiometry and otoacoustic emissions. INTERVENTION: All subjects were exposed to 0, 20, and 35 dB effective masking (EM) of white noise during monotic and diotic click stimulation. DATA COLLECTION AND ANALYSIS: ABR and MLR responses were simultaneously acquired. Peak amplitudes and latencies were recorded and compared across conditions using a repeated measures analysis of variance (ANOVA). RESULTS: For BE, ABR results showed enhancement at 0 and 20 dB EM, but not at 35 dB EM. The MLR showed BE at all noise levels, but the degree of BE decreased with increasing noise level. For BI, both the ABR and MLR showed BI at all noise levels. However, the degree of BI again decreased with increasing noise level for the MLR. CONCLUSIONS: The results demonstrate the ability to measure BE simultaneously in the ABR and MLR in up to 20 dB of EM noise and BI in up to 35 dB EM of noise. Results also suggest that ABR neural generators may respond to noise differently than MLR generators.

Cortical thickness in congenital amusia: when less is better than more.

Congenital amusia (or tone deafness) is a lifelong disorder characterized by impairments in the perception and production of music. A previous voxel-based morphometry (VBM) study revealed that amusic individuals had reduced white matter in the right inferior frontal gyrus (IFG) relative to musically intact controls (Hyde et al., 2006). However, this VBM study also revealed associated increases in gray matter in the same right IFG region of amusics. The objective of the present study was to better understand this morphological brain anomaly by way of cortical thickness measures that provide a more specific measure of cortical morphology relative to VBM. We found that amusic subjects (n = 21) have thicker cortex in the right IFG and the right auditory cortex relative to musically intact controls (n = 26). These cortical thickness differences suggest the presence of cortical malformations in the amusic brain, such as abnormal neuronal migration, that may have compromised the normal development of a right frontotemporal pathway.