Absent Auditory Brainstem Responses Research Articles

Short-term outcomes of infants with hyperbilirubinemia-associated auditory neuropathy spectrum disorder in neonatal intensive care unit

Hyperbilirubinemia is a high-risk factor for auditory neuropathy spectrum disorder (ANSD) as well as hearing loss in general. This study described the outcomes of hyperbilirubinemia-associated ANSD infants diagnosed in hearing screening in the neonatal intensive care unit (NICU).A total of 578 children with hyperbilirubinemia admitted to the NICU between October 2020 and October 2021 were included in this study. The distortion product otoacoustic emission (DPOAE) and automatic auditory brainstem response (AABR) were combined for hearing screening, and those who failed the DPOAE or/and AABR underwent an auditory brainstem response (ABR) test. Infants with ANSD were followed up for 12 months.Forty infants (40/578, 6.9%) failed the DPOAE or/and AABR tests, of which, 13 (13/578, 2.2%) were diagnosed as ANSD, and 27 (27/578, 4.7%) were diagnosed as having sensorineural hearing loss (SNHL). Of the 13 ANSD infants followed up for 12 months, 7 recovered, 3 improved, 3 did not recover, and 1 was lost, equating to improved or recovered hearing in 75% (9/12) of ANSD infants at 12 months of age. Moreover, the maximum bilirubin in recovered or improved ANSD infants was 408.6 ± 129.0 μmol/L, while the maximum bilirubin in unrecovered ANSD infants was 749.3 ± 323.0 μmol/L. Furthermore, poorly differentiated and absent ABR waveforms were observed in 6 and 14 ears at 1 month, 2 ears were lost, 6 (6/6, 100.0%) and 6 (6/12, 50.0%) ears were recovered or improved at 12 months of age.s: The incidence of hyperbilirubinemia associated-ANSD was 2.2% of infants screened in the NICU. ANSD caused by hyperbilirubinemia may be transient, with most infants improving or recovering hearing by 12 months of age. Infants with poorly differentiated ABR waveforms and low bilirubin concentration are more likely to recover and hearing aids are not recommended in hyperbilirubinemia-associated ANSD below 12 months of age.

Apoptosis of type I spiral ganglion neuron cells in Otof-mutant mice

Otof, which encodes otoferlin, knockout mice are considered model mice for auditory neuropathy spectrum disorder, which is characterized by an absent auditory brainstem response (ABR) despite preserved distortion product otoacoustic emission (DPOAE). Although otoferlin-deficient mice lack neurotransmitter release at the inner hair cell (IHC) synapse, it remains unclear how the Otof mutation affects spiral ganglions. Thus, we used Otof-mutant mice carrying the Otoftm1a(KOMP)Wtsi allele (Otoftm1a) and analyzed spiral ganglion neurons (SGNs) in Otoftm1a/tm1a mice by immunolabeling type Ⅰ SGNs (SGN-Ⅰ) and type II SGNs (SGN-II). We also examined apoptotic cells in SGNs. Four-week-old Otoftm1a/tm1a mice had an absent ABR but normal DPOAEs. The number of SGNs was significantly lower in Otoftm1a/tm1a mice on postnatal day 7 (P7), P14, and P28 compared with that of wild-type mice. Moreover, significantly more apoptotic SGNs were observed in Otoftm1a/tm1a mice than in wild-type mice on P7, P14, and P28. SGN-IIs were not significantly reduced in Otoftm1a/tm1a mice on P7, P14, and P28. No apoptotic SGN-IIs were observed under our experimental conditions. In summary, Otoftm1a/tm1a mice showed a reduction in SGNs accompanied by apoptosis of SGN-Ⅰs even before the onset of hearing. We speculate that the reduction in SGNs with apoptosis is a secondary defect caused by a lack of otoferlin in IHCs. Appropriate glutamatergic synaptic inputs may be important for the survival of SGNs.

Prevalence, risk factors, and audiological characteristics of auditory neuropathy

Objective The objective of this study was to determine the prevalence, risk factors, and audiological characteristics of auditory neuropathy spectrum disorder (ANSD) in the pediatric population. Design A retrospective review of medical charts was conducted for children visiting two hospitals in Saudi Arabia. Study Sample Medical records of 1025 patients with sensorineural hearing loss (SNHL) were reviewed. We analyzed the databases for results of audiological examinations, risk factors, and outcomes of intervention including hearing aid (HA) and cochlear implantation (CI). Results Out of 1025 children with SNHL, 101 patients (9.85%) were identified to have ANSD. Audiological characteristics of the ANSD group revealed a severe-to-profound degree of hearing loss, all showed type A tympanogram and absent reflexes, absent auditory brainstem response (ABR) findings with present cochlear microphonic while otoacoustic emissions were absent in 54.5% of patients. The most prevalent risk factors for ANSD in this group were family history of hearing loss, consanguinity, hyperbilirubinemia, and low birth weight. Pure tone and speech detection thresholds improved significantly with CI compared to HA use in this sample of patients with ANSD. Conclusion This study shows that ANSD is not extremely rare among Saudi children with severe to profound hearing loss, with a prevalence of 9.85%.

Prevalence, behavioural, and management outcomes of infants with auditory neuropathy spectrum disorder.

To provide an overview of electrophysiological and behavioural outcomes from a large UK centres data set on children diagnosed with auditory neuropathy (ANSD) between 2002 and March 2018. A systematic audit was undertaken, collating the electrophysiological data from auditory brainstem response (ABR) follow-up, risk factors, and later behavioural results/management. These were then compared to look for trends between groups. The study sample consisted of 118 925 infants born, with 46 (0.039%, 0.39 per 1000 births) being diagnosed with congenital ANSD (39 bilateral, seven unilateral). Twenty-nine per cent of ears with ANSD had short latency components on ABR testing. Forty-four per cent of ears with present cochlear microphonics but absent transient-evoked otoacoustic emissions (TE-OAE) and no ABR went on to have profound behavioural hearing threshold levels. All but one child went on to show a hearing loss on behavioural testing. ANSD was not confined to the population from neonatal intensive care units: there were three bilateral and five unilateral cases in the typically developing infant population. The incidence of ANSD is higher in this sample than that reported previously in the literature. Children who had cochlear microphonics with absent ABR and absent TE-OAE had significantly worse later behavioural outcomes than other patterns of electrophysiological results.

Familial Temperature-Sensitive Auditory Neuropathy: Distinctive Clinical Courses Caused by Variants of the OTOF Gene.

Objective: To investigate the clinical course and genetic etiology of familial temperature-sensitive auditory neuropathy (TSAN), which is a very rare subtype of auditory neuropathy (AN) that involves an elevation of hearing thresholds due to an increase in the core body temperature, and to evaluate the genotype–phenotype correlations in a family with TSAN.Methods: Six members of a non-consanguineous Chinese family, including four siblings complaining of communication difficulties when febrile, were enrolled in this study. The clinical and audiological profiles of the four siblings were fully evaluated during both febrile and afebrile episodes, and the genetic etiology of hearing loss (HL) was explored using next-generation sequencing (NGS) technology. Their parents, who had no complaints of fluctuating HL due to body temperature variation, were enrolled for the genetics portion only.Results: Audiological tests during the patients’ febrile episodes met the classical diagnostic criteria for AN, including mild HL, poor speech discrimination, preserved cochlear microphonics (CMs), and absent auditory brainstem responses (ABRs). Importantly, unlike the pattern observed in previously reported cases of TSAN, the ABRs and electrocochleography (ECochG) signals of our patients improved to normal during afebrile periods. Genetic analysis identified a compound heterozygous variant of the OTOF gene (which encodes the otoferlin protein), including one previously reported pathogenic variant, c.5098G > C (p.Glu1700Gln), and one novel variant, c.4882C > A (p.Pro1628Thr). Neither of the identified variants affected the C2 domains related to the main function of otoferlin. Both variants faithfully cosegregated with TSAN within the pedigree, suggesting that OTOF is the causative gene of the autosomal recessive trait segregation in this family.Conclusion: The presence of CMs with absent (or markedly abnormal) ABRs is a reliable criterion for diagnosing AN. The severity of the phenotype caused by dysfunctional neurotransmitter release in TSAN may reflect variants that alter the C2 domains of otoferlin. The observations from this study enrich the current understanding of the phenotype and genotype of TSAN and may lay a foundation for further research on its pathogenesis.

Auditory Steady-State Response (ASSR) in hearing-impaired children with absent Auditory Brainstem Response (ABR) waves

Objectives: The aim of this work was to evaluate the residual hearing in children with sensorineural hearing loss and absent ABR waves by ASSR to select the appropriate way for intervention either the use of hearing aid or cochlear implant. Patients and methods: Forty children (80 ears) were included in this study in the period from May 2019 up to April 2020. All children had detailed complete history taking, otoscopic examination, immittancemetry, hearing assessment to get an accurate frequency specific threshold with play audiometry, behavioral observation audiometry, and evoked audiometry including ABR, TEOAEs, and ASSR. Results: Forty hearing impaired children with ages ranged from 1 to 5 years old, 22 were males and 18 were female. ASSR response was obtained from 53 ears, and 27 ears showed no response. The ASSR showed a better response at low-frequency regions when compared to the high-frequency regions but with no statistically significant difference. Conclusions: The absence of click-ABR waves and behavioral free-field responses do not rule out the presence of residual hearing. ASSR was done to estimate the residual hearing mainly at low-frequency regions.

Neurodegenerative Diseases and the Auditory-Vestibular System

Neurodegenerative Diseases and the Auditory-Vestibular System

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

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 normal-hearing individuals. Methods A total of 50 individuals participated in the present study, in which Group I comprised 25 normal-hearing individuals, and Group II comprised 25 individuals with ANSD. 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 chi-squared 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.

Auditory neuropathy spectrum disorder (ANSD) in referrals from neonatal hearing screening at a well-baby clinic.

Auditory neuropathy spectrum disorder (ANSD) is a particular kind of hearing disorder characterised by normal outer hair cell function and abnormal or absent auditory brain stem responses. Little data are available regarding the prevalence of this condition in healthy newborns. We performed a retrospective medical records review of 791 referrals from universal neonatal hearing screening (UNHS) at a well-baby clinic to investigate the prevalence of ANSD. Hearing screening was performed by automated auditory brain stem response (ABR) testing. A diagnosis of ANSD was established when ABR tracings were absent in the presence of otoacoustic emissions and/or a cochlear microphonic. Amongst 201 infants with confirmed congenital hearing loss, 13 infants were diagnosed with ANSD. The condition was unilateral in six and bilateral in seven infants. A risk factor for hearing loss could be identified in three infants. Abnormalities on magnetic resonance imaging were found in six infants; five of them had cochlear nerve deficiency. The prevalence of ANSD was 6.5% amongst well babies with confirmed congenital hearing loss identified through UNHS. The estimated incidence of ANSD in our population of newborns at the well-baby clinic was 0.09/1000 live births. Magnetic resonance revealed an underlying anatomical abnormality in about half of the patients. • Auditory neuropathy dyssynchrony spectrum disorder (ANSD) is a particular form of hearing loss, mostly encountered in neonatal intensive care unit (NICU) graduates. • Little data are available on the prevalence and risk factors for ANSD in healthy newborns. What is new: • The estimated prevalence of ANSD in healthy newborns is 0.09/1000 live births. • In about half of the healthy newborns with ANSD, a structural abnormality was detected on magnetic resonance imaging of the posterior fossa/brain.

The Yin and Yang of Auditory Nerve Damage

Chambers et al. investigate consequences in the central auditory system after profound cochlear denervation. They observed gains in firing rate in auditory cortex despite nearly absent auditory nerve and brainstem responses, suggesting an important role of central plasticity and its clinical implications.

Timescales of Auditory Processing

Timescales of Auditory Processing

Subjective and Objective Estimate of Neural Fatigue in an Adult with Auditory Neuropathy Spectrum Disorder

Auditory neuropathy spectrum disorder (ANSD) is a retrocochlear disorder in which cochlear functioning is normal but the transmission in the auditory neural pathway is affected. The present study reports of neural fatigue seen in subjective and objective tests of adaption in a 19 year old adult with ANSD. He had bilateral mild sensorineural hearing loss with otoacoustic emissions present and absent auditory brainstem response. Immittance evaluation showed elevated acoustic reflexes at 500 Hz and 1000 Hz in both ipsilateral and contralateral stimulation. Reflex decay test was administered at 500 Hz and 1000 Hz which showed positive reflex decay with contralateral stimulation. Olsen and Noffsinger tone decay test and supra-threshold adaptation test showed positive tone decay at 500 Hz, 1000 Hz and 2000 Hz in both ears. The results of the study showed positive reflex decay and positive tone decay which indicate abnormal neural fatigue. The abnormal neural firing seen in individuals with ANSD could have resulted in positive reflex decay and tone decay. However, further studies on larger group of population are essential for further understanding the mechanisms in detail.

Amplification Options in Children with Auditory Neuropathy Spectrum Disorder

Auditory neuropathy spectrum disorder (ANSD) is a specific form of hearing loss characterized by the presence of normal or near-normal Otoacoustic Emissions (OAEs) but the absence of normal middle ear muscle reflex and severely abnormal or completely absent auditory brainstem response (ABRs). Amplification is considered a dilemma in such disorder with a lot of debates. This article will review hearing aids and cochlear implant as options for management in ANSD.

Audiological changes over time in adolescents and young adults with auditory neuropathy spectrum disorder.

Auditory neuropathy spectrum disorder (ANSD) describes a condition in which a patient's otoacoustic emissions (OAE) are (or were at one time) present and auditory brainstem responses (ABR) are abnormal or absent. ANSD is also diagnosed based on the presence of cochlear microphonics and abnormal or absent ABRs with or without abnormalities of OAE. We noted the changes in audiological characteristics over time with respect to pure tone thresholds, OAEs and Speech Identification Scores (SIS) in seven individuals with ANSD. The results indicated that all the individuals with ANSD had decreased SIS over time, whereas there was subsequent reduction in pure tone thresholds only in nine out of fourteen ears. There was absence of OAEs for two individuals in both ears during the follow-up evaluations. There was no regular pattern of changes in pure tone thresholds or SIS across all individuals. This indicates that there may be gradual worsening of hearing abilities in individuals with ANSD. Thus, regular follow-up and monitoring of audiological changes are necessary for individuals with ANSD. Also, longitudinal studies need to be done to further add evidence to the audiological changes over time in individuals with ANSD.

Auditory Steady State Response (ASSR) Frequency-Specific Thresholds with Absent Auditory Brainstem Response (click-ABR) Test Results among Filipino Children

Objective: Determine the frequency-specific thresholds of auditory steady state response (ASSR) of Filipino children with absent auditory brainstem response (click-ABR) results.
 
 Methods:
 This is a cross-sectional study analyzing the frequency-specific thresholds of auditory steady state response (ASSR) of Filipino children with absent auditory brainstem response (click-ABR) results. The study population comprised of 99 pediatric patients referred for hearing assessment using electrophysiologic techniques at the Ear Unit of the Philippine General Hospital. The subjects underwent hearing threshold evaluation using both evoked-potential techniques (click ABR and ASSR) within a 1-month period from January 2009 to March 2014. The ASSR results of patients with absent click-ABR were collected and analyzed.
 Results: There were 99 patients who underwent both ABR and ASSR. Of the 65 patients with absent ABR thresholds results, 13 patients had unilateral absent ABR while 52 had bilateral absent ABR results. The data of hearing tests from the combined 117 ears with absent ABR hearing tests were collected.
 The proportion of children with ASSR thresholds with absent ABR per frequency were:
 
 500 Hz - 45/117 (38.5 %);
 1000 Hz - 76/117 (64.0 %);
 2000 Hz - 63/117 (53.8 %); and
 4000 Hz - 41/117 (35.0 %).
 
 The proportion of children with ASSR thresholds with absent ABR per number of frequencies were:
 
 4 frequencies - 19/117 (16.2 %);
 3 frequencies - 32/117 (27.4 %);
 2 frequencies - 22/117 (18.8 %); and
 1 frequency - 44/117 (37.6%)
 
 Conclusion: In the absence of click- ABR response, ASSR may provide information about the levels of severe to profound hearing loss among children. The criteria of selection of candidates for intervention (hearing aids or cochlear implantation) should include results from hearing evaluation not only from behavioral and ABR thresholds but also from ASSR thresholds. This may ensure that exclusion of some children with severe and profound hearing loss who may benefit from the intervention will be minimized.
 
 Keywords: profound sensorineural deafness, evoked response audiometry, hearing thresholds

Perinatal Medical Risks Associated with Auditory Neuropathy Spectrum Disorder

Objectives: (1) Determine perinatal medical factors associated with auditory neuropathy spectrum disorder (ANSD). (2) Compare risk factors associated with ANSD to those in sensorineural hearing loss (SNHL). Methods: Retrospective case-control study of children diagnosed with ANSD at an academic tertiary care center between July 2009 and January 2014. Inclusion criteria for the ANSD group were normal otoacoustic emissions, absent or elevated middle-ear muscle reflexes, and severely abnormal or absent auditory brainstem response waveforms. The ANSD group was compared with 2 age- and sex-matched control groups: (1) normal-hearing children and (2) children with SNHL. Results: Twenty-two patients (15 male, 7 female) met ANSD inclusion criteria, and were matched to 2 control groups as described above. Case and control groups were assessed for the following perinatal risk factors: prematurity, low birth weight, hyperbilirubinemia, mechanical ventilation, and administration of ototoxic antibiotics. On multivariate logistic regression between ANSD and normal-hearing groups, hyperbilirubinemia ( P = .006) and administration of ototoxic antibiotics ( P = .004) were significantly associated with an increased odds ratio (OR) toward developing ANSD. Comparing ANSD and SNHL groups, the only significant risk factor for development of ANSD was hyperbilirubinemia ( P = .005, odds ratio = 12). Conclusions: ANSD, a clinical spectrum of disease united by normal cochlear function but abnormal auditory pathway transduction, remains an enigmatic entity. In the present study, matched comparisons between ANSD versus normal-hearing and SNHL control groups identified perinatal hyperbilirubinemia and ototoxic antibiotics as significant risk factors. Diligent hearing evaluation to diagnose ANSD in infancy, particularly among patients with a perinatal history of hyperbilirubinemia, is critical.

Audiological profiling of 198 individuals with auditory neuropathy spectrum disorder

Objective: The study aimed at exploring the audiological characteristics and the relationship between speech identification scores with cortical evoked potential measures and hearing aid benefit in individuals with auditory neuropathy spectrum disorder (ANSD). Study design: We initiated a retrospective study of patients who were diagnosed as having ANSD. In 198 patients with ANSD, patient history, risk factors, degree and configuration of hearing loss, speech identification scores in quiet and noise, otoacoustic emissions (OAE), immittance evaluation, auditory brainstem responses (ABR), long latency responses (LLR) and hearing aid benefit were assessed. Results: The results showed that the majority of the patients had bilateral ANSD with a female to male ratio of 1.25:1 with the majority having a rising configuration of hearing loss. OAEs were present in most with absent stapedial reflexes and ABR. The study also showed that individuals with ANSD do obtain benefit from hearing aids and it is related to the presence of LLR. Conclusions: The present study emphasizes the audiological characteristics of a large group with ANSD. Among the management options, hearing aids were found to be useful in only a few of the patients and other rehabilitation options, such as cochlear implants, need to be explored in future studies. Currently, the determining factors for benefit with hearing aid are speech identification scores and cortical auditory evoked potentials.

An auditory profile of sclerosteosis.

Objective: To characterise auditory involvement secondary to excessive craniotubular bone growth in individuals with sclerosteosis in South Africa. Methods: This cross-sectional study assessed the auditory profile of 10 participants with sclerosteosis. An auditory test battery was used and results for each ear were recorded using descriptive and comparative analyses. Results: All participants presented with bilateral, mixed hearing losses. Of the 20 ears, hearing loss was moderate in 5 per cent (n=1), severe in 55 per cent (n=11) and profound in 40 per cent (n=8). Air-bone gaps were smaller in older participants, although the difference was not statistically significant (p>0.05). Computed tomography scans indicated pervasive abnormalities of the external auditory canal, tympanic membrane, middle-ear space, ossicles, oval window, round window and internal auditory canal. Narrowed internal auditory canals corresponded to poor speech discrimination, indicative of retrocochlear pathology and absent auditory brainstem response waves. Conclusion: Progressive abnormal bone formation in sclerosteosis involves the middle ear, the round and oval windows of the cochlea, and the internal auditory canal. The condition compromises conductive, sensory and neural auditory pathways, which results in moderate to profound, mixed hearing loss.

Long Ringing Cochlear Microphonics - Not Unique to Auditory Neuropathy Spectrum Disorder in Children

Long Ringing Cochlear Microphonics - Not Unique to Auditory Neuropathy Spectrum Disorder in Children Background: The detection of cochlear microphonics in surface recordings has been considered a distinctive sign of outer hair cell integrity in participants with auditory neuropathy spectrum disorder. The study highlights that this notion could result in misdiagnosis of patients. Methods: The study reports three children with sloping hearing loss who were misdiagnosed as auditory neuropathy spectrum disorder based on absence of auditory brainstem response and presence of long ringing cochlear microphonics. The study also reports of three children with abnormal cochlear microphonics who have neurological abnormalities. Results: The abnormal cochlear microphonics (long ringing) with absent auditory brainstem response was noted in sloping hearing loss participants. In addition, abnormal cochlear microphonics was also observed along with auditory brainstem response in children with neurological abnormalities. Conclusion: Our results show that abnormal CM detection in surface recording is not a distinctive feature of auditory neuropathy spectrum disorder and participants who are diagnosed with auditory neuropathy spectrum disorder based on traditional diagnostic criteria should be reviewed to rule out possible misdiagnosis.

Auditory steady-state response audiometry in children with severe to profound sensorineural hearing loss

Objective The aim of the study was to find out the predictive value of single monotic auditory steady-state response (ASSR) for hearing threshold estimation in children with severe to profound sensorineural hearing loss (SNHL). Methodology Forty-eight children (96 ears) with severe to profound SNHL were included in the present study, with age range 1-10 years. They were subjected to age-based audiological evaluation to estimate the behavioral thresholds. Single monotic ASSR was performed for all children using test signals of 250, 500, 1000, 2000, and 4000 Hz, modulated in both ears at high rates of 67, 74, 81, 88, and 95 Hz, respectively, using GSI Audera-evoked potential system. ASSR thresholds were obtained and analyzed according to the equipment default criteria. Results The number and percentage of ASSR detected were highest at 1000 Hz then 500 Hz followed by 2000 Hz and were the least at 4000 and 250 Hz in all children. The ASSR thresholds obtained were statistically correlated with the behavioral pure tone audiometry thresholds at 500, 100, and 2000 Hz. A considerable number of ears with no sound field thresholds or click auditory brainstem response responses showed ASSR. Conclusion Single monotic ASSR, with high modulation frequencies, has proven to be a reasonable method for estimating hearing sensitivity in the mid-conventional audiometric frequencies in children with severe to profound SNHL. Recommendations All children with no behavioral hearing threshold and/or absent click-evoked auditory brainstem response should be tested by ASSR at 500, 1000, and 2000 Hz to give information about the presence of useful residual hearing. ASSR can provide important information for use in the cochlear implant selection process