Auditory Neuropathy/auditory Dys-synchrony Research Articles

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 / Auditory Dyssynchrony in children with Cochlear Implants

AbstractThe electrical stimulation generated by the Cochlear Implant (CI) may improve the neural synchrony and hence contribute to the development of auditory skills in patients with Auditory Neuropathy / Auditory Dyssynchrony (AN/AD). AimProspective cohort cross-sectional study to evaluate the auditory performance and the characteristics of the electrically evoked compound action potential (ECAP) in 18 children with AN/AD and cochlear implants. Material and methodsThe auditory perception was evaluated by sound field thresholds and speech perception tests. To evaluate ECAP's characteristics, the threshold and amplitude of neural response were evaluated at 80Hz and 35Hz. ResultsNo significant statistical difference was found concerning the development of auditory skills. The ECAP's characteristics differences at 80 and 35Hz stimulation rate were also not statistically significant. ConclusionThe CI was seen as an efficient resource to develop auditory skills in 94% of the AN/ AD patients studied. The auditory perception benefits and the possibility to measure ECAP showed that the electrical stimulation could compensate for the neural dyssynchrony caused by the AN/AD. However, a unique clinical procedure cannot be proposed at this point. Therefore, a careful and complete evaluation of each AN/AD patient before recommending a Cochlear Implant is advised. Clinical Trials: NCT01023932

Saccular dysfunction in children with sensorineural hearing loss and auditory neuropathy/auditory dys-synchrony

Conclusion: There is a correlation between the AN/AD disorder and the saccular dysfunction in children with severe sensorineural hearing loss, which means that saccular dysfunction can be a concomitant sign of AN/AD. In conclusion, the term of audio-vestibular dys-synchrony (AVS) is a more suitable description for this condition. Objectives: Patients with auditory neuropathy/auditory dys-synchrony (AN/AD) characteristically demonstrate poor neural responses from the vestibulocochlear nerve and brainstem while displaying evidence of intact outer hair cells function. Therefore, the objective of this study is studying of the relationship of the saccular dysfunction with AN/AD disorder in children with sensorineural hearing loss. Methods: In this cross-sectional study, 100 children with bilateral severe-to-profound sensorineural hearing losses underwent audiologic tests and cervical vestibular-evoked myogenic potentials (cVEMPs) at the Audiology Department of Hamadan University of Medical Sciences (Hamadan, Iran). Results: Eleven children with bilateral severe sensorineural hearing loss were given to unilateral AN/AD disorder (11 ears), and two children (4 ears) had bilateral AN/AD (total = 13 children). The ears with AN/AD took the form of unrepeatable or absent waves of ABR and presence of OAEs. The statistical analysis of an independent t-test between AN/AD ears as compared to non-AN/AD ears of these 13 children showed that the mean latencies of p13 and the mean latencies of n23 and the mean peak-to-peak amplitude had significant differences.

Identification of a novel splice site variant of OTOF in the Korean nonsyndromic hearing loss population with low prevalence of the OTOF mutations

Purpose(1) To describe the frequency of the OTOF mutations among Korean ARNSHL (autosomal recessive nonsyndromic hearing loss) populations; (2) to report the vertical transmission of DFNB9 in a family, where two related DFNB9 patients in the family manifested a different audiological phenotype. MethodWe analyzed the prevalence of OTOF mutations among 71 Korean sporadic or possible ARNSHL pediatric patients, as well as among AN/AD (auditory neuropathy/auditory dys-synchrony) patients by direct PCR (polymerase chain reaction) sequencing or targeted resequencing of known deafness genes. ResultsThe AN/AD phenotype which was characterized by preservation of OAE (otoacoustic emission) was present in 5 (7%) of 71 probands, and the prevalence of OTOF mutations was calculated to be 20% (1/5) and 1.4% (1/71) among AN/AD patients and total sporadic/ARNSHL patients, respectively. PJVK mutations did not account for Non-DFNB9 AN/AD patients. To our interest, the only proband (SB4-11) with two OTOF mutant alleles in our cohort had deaf parents, who also turned out to be DFNB9. We identified a novel splice site variant of OTOF from the mother (SB4-13) of SB4-11. This was the first observation of vertical transmission of DFNB9 phenotype from parents to son in this population where the prevalence of OTOF is very low and consanguineous marriage is not allowed. Another DFNB9 patient (SB4-12), the father of SB4-11, carried a homozygous p.Y374X mutation that affected only the long isoform of OTOF and did not manifest AN/AD. ConclusionThe OTOF mutations do not contribute significantly to Korean ARNSHL and AN/AD unlike in Japan and Taiwan. This low prevalence mandates a search for other etiologies. Our observation of the discordant audiologic phenotype within the same DFNB9 family is more likely due to the loss of OAE over time rather than a genotype–phenotype correlation.

Evidence for genotype–phenotype correlation for OTOF mutations

ObjectivesThe aim of this study is to evaluate the auditory phenotype in subjects with OTOF gene mutations to describe genotype–phenotype correlations. MethodsTwenty-two affected members from three families with homozygous OTOF mutations were included. Nine subjects were evaluated audiologically with otoscopic examination, pure-tone audiometry, tympanometry with acoustic reflex testing, auditory brain stem responses, and otoacoustic emission tests. ResultsHomozygous c.4718T>C (p.Ile1573Thr) mutation was associated with the auditory neuropathy/auditory dys-synchrony (AN/AD) phenotype and with progressive sensorineural hearing loss in four siblings in one family, while homozygous c.4467dupC (p.I1490HfsX19) was associated with severe to profound sensorineural hearing loss without AN/AD in four relatives in another family. Homozygous c.1958delC (p.Pro653LeufsX13) mutation was associated with moderate sensorineural hearing loss without AN/AD in one affected person in an additional family. ConclusionsThe audiological phenotype associated with different OTOF mutations appears to be consistently different suggesting the presence of a genotype–phenotype correlation.

Developmental outcomes of children with auditory neuropathy/dyssynchrony (auditory neuropathy spectrum disorder)

Background This paper reviews current knowledge about the developmental outcomes of children with auditory neuropathy/auditory dyssynchrony (ANAD). Aim The article discusses the diverse variables that can impact developmental outcomes of this population of children with hearing loss and what is currently known in the literature. Since two-thirds of the children with ANAD have additional disabilities, this population of children is very complex. Patients The article discusses three children with very diverse developmental profiles including the differential diagnostic evaluations that supported decisions about communication approaches. Methods Three case histories of children with ANAD representing different individual characteristics and developmental trajectories are discussed. These three cases were chosen to represent the diversity of the population of children with ANAD. Results Case A is a child who received bilateral cochlear implantation and successfully developed listening and spoken language skills. Case B is a child who received bilateral cochlear implantation which did not result in successful listening and spoken language because of a breakdown at the level of the auditory cortex but is using sign language as a primary approach to learn to communicate. Case C is a child with significant co-morbidities including cerebral palsy and global developmental delays who is communicating through both spoken and signed language without the use of amplification. Conclusion Children with ANAD have significant diversity in their ability to access spoken language without amplification, with hearing aids and with cochlear implants. However, despite this diversity, when children are provided access to language through individualization and appropriate matching of both auditory and visual communication approaches, they can become successful language learners.

A Tutorial on Auditory Neuropathy/Dyssynchrony for the Speech-Language Pathologist and Audiologist

This article presents information about developmental outcomes of children with auditory neuropathy/auditory dyssynchrony (AN). Colorado data on the number of children screened and the number of children identified with unilateral and bilateral AN will be described. Descriptive information about the percent of children with AN with cognitive disability and disabilities other than hearing loss will be presented. Language outcomes of children with normal cognitive development will be presented. This article will also provide information about etiologies and audiological information of children with AN. It includes assessment tools that have been useful in decision making for children with AN.

Adults with Auditory Neuropathy: Comparison of Auditory Steady-State Response and Pure-Tone Audiometry

The relation between the auditory steady-state response (ASSR) and behavioral audiometric thresholds requires further clarification in the case of adults with auditory neuropathy/auditory dys-synchrony (AN/AD). The aim of this study was to compare pure-tone audiometric threshold (PTAT) and ASSR in adults with AN/AD. Sixteen adult participants (32 ears) with AN/AD, ranging in age from 14 to 34 years. PTAT and ASSR with high-rate stimulus modulation were measured at four octave frequencies, 500, 1000, 2000, and 4000 Hz, in each ear. The behavioral auditory thresholds were compared with ASSR estimated thresholds at each frequency. Analyses included comparison of group means and coefficients of correlation. The average pure-tone thresholds revealed a moderate hearing loss in the AN/AD patients with a focus on the low frequencies. Low-frequency loss audiograms were observed in almost two-thirds of the participants. The estimated auditory thresholds measured by ASSR at all frequencies were substantially higher than the PTAT measures. There were no significant correlations between the PTAT and ASSR measurements at the 1000, 2000, and 4000 Hz frequencies (p > .05); the correlation between the two measures at 500 Hz (p = .029, r = 0.39) was weak but significant. There was no significant correlation between the PTAT and ASSR results at the majority of the frequencies usually tested in adults with AN/AD. Although ASSR is not a suitable method to estimate auditory thresholds in this group of patients, perhaps it can be utilized as an adjunct technique for the differential diagnosis of this disorder.

The frequency of auditory neuropathy detected by universal newborn hearing screening program

Auditory neuropathy/auditory dyssynchrony (AN/AD) has become a well-accepted clinical entity. The combined use of oto-acoustic emissions (OAEs) and auditory brainstem response (ABR) testing in the universal newborn hearing screening (UNHS) has led to the easy recognition of this disorder. Although, we are now able to diagnose AN/AD reliably, little is known about its epidemiology, etiology, and especially the frequency of its occurrence. The primary goal of this study was to determine the frequency of AN/AD in the Western Anatolian region of Turkey. The secondary goal was to compare the detection rate of AN/AD before and after the implementation of the UNHS in the audiology department of Dokuz Eylul University Hospital. Between 2005 and 2007, among the 23,786 newborns who were screened by automated click evoked oto-acoustic emissions (a-CEOAE) and automated auditory brainstem responses (a-ABRs), 2236 were referred to our department. All necessary audiological tests were performed for all the referred newborns. Among them, babies with deficient or abnormal ABR in combination with normal OAEs were considered as having AN/AD. These babies were evaluated with additional diagnostic audiological tests. Furthermore, comparison of the incidence of children diagnosed with AN/AD before and after the implementation of UNHS in our audiology department was also performed. Among the referred newborns, 65 had abnormal or deficient ABR test results. Ten of these 65 newborn babies (mean diagnostic age: 5.7 months) with hearing impairment showed electrophysiological test results that were consistent with AN/AD. The frequency of AN/AD in these 65 children with hearing loss was 15.38%. Moreover, the frequency of AN/AD within UNHS was found to be 0.044%. Seven of the 10 babies with AN/AD had hyperbilirubinemia as a risk factor, which is a high rate to be emphasized. On the other hand, the retrospective investigation of children diagnosed with AN/AD in the same audiology department between 1999 and 2005 (i.e. before the implementation of UNHS) revealed only 7 children, with an average diagnostic age of 34 months. After implementing the UNHS, the incidence of AN/AD in the audiology department increased from 1.16 to 4.13. Furthermore, the age of diagnosis of AN/AD decreased from 34 months to 5.7 months. This study shows that AN/AD, when screened, is a comparatively common disorder in the population of hearing-impaired infants. While newborn hearing screening provides early detection of babies with hearing loss, it also helps to differentiate AN/AD cases when the screening is performed with both a-ABR and automated oto-acoustic emission (a-OAE) tests. Thus, the routine combined use of a-ABR and a-OAE tests in UNHS programs, especially for the high-risk infants, can provide better detection of newborns with AN/AD. Furthermore, hyperbilirubinemia is merely an association and maybe etiologically linked.

Intervention for a Child with Auditory Neuropathy/Dys-synchrony

Intervention for a Child with Auditory Neuropathy/Dys-synchrony

Cochlear microphonics in sensorineural hearing loss: Lesson from newborn hearing screening

The diagnostic dilemma surrounding the presence of cochlear microphonics (CM) coupled with significantly elevated auditory brainstem response (ABR) thresholds in babies failing the newborn hearing screening is highlighted. A case report is presented where initial electo-diagnostic assessment could not help in differentiating between Auditory Neuropathy/Auditory Dys-synchrony (AN/AD) and sensorineural hearing loss (SNHL). In line with the protocol and guidelines provided by the national Newborn Hearing Screening Programme in the UK (NHSP) AN/AD was suspected in a baby due to the presence of CM at 85 dBnHL along with click evoked ABR thresholds of 95 dBnHL in one ear and 100 dBnHL in the other ear. Significantly elevated thresholds for 0.5 and 1kHz tone pip ABR fulfilled the audiological diagnostic criteria for AN/AD. However, the possibility of a SNHL could not be ruled out as the 85 dBnHL stimuli presented through inserts for the CM would have been significantly enhanced in the ear canals of the young baby to exceed the threshold level of the ABR that was carried out using headphones. SNHL was eventually diagnosed through clinical and family history, physical examination and imaging that showed enlarged vestibular aqueducts. Presence of CM in the presence of very high click ABR thresholds only suggests a pattern of test results and in such cases measuring thresholds for 0.5 and 1 kHz tone pip ABR may not be adequate to differentiate between SNHL and other conditions associated with AN/AD. There is a need for reviewing the existing AN/AD protocol from NHSP in the UK and new research to establish parameters for CM to assist in the differential diagnosis. A holistic audiological and medical approach is essential to manage babies who fail the newborn hearing screening.

Contemporary Audiologic Assessment for Auditory Dys-Synchrony

Contemporary Audiologic Assessment for Auditory Dys-Synchrony

Eletrococleografia extratimpânica na neuropatia/dessincronia auditiva

O potencial evocado auditivo de tronco encefálico (PEATE) vem sendo amplamente utilizado como método para avaliação da função coclear em indivíduos com diagnóstico de neuropatia/dessincronia auditiva (NA/DA). Na ausência das emissões otoacústicas, muitos casos de NA/DA foram diagnosticados pela presença do microfonismo coclear (MC) identificado no PEATE. OBJETIVO: Demonstrar a aplicabilidade clínica da eletrococleografia extratimpânica (Ecog-ET) no diagnóstico diferencial da NA/DA quando comparada ao PEATE. MATERIAL E MÉTODO: Uma criança com 4 anos de idade, com diagnóstico de NA/DA atendida no Centro de Pesquisas Audiológicas realizou a Ecog-ET com tone burst de 2000Hz nas polaridades de rarefação e condensação. RESULTADOS: Ilustrou-se o registro da Ecog-ET. Com a utilização de protocolo apropriado, o MC pode ser evidenciado e confirmado na Ecog, com qualidade de registro superior ao obtido no PEATE. CONCLUSÃO: A Ecog-ET permitiu uma análise mais detalhada do MC quando comparada ao PEATE tendo, portanto aplicabilidade clínica na investigação da função coclear na NA/DA.

Factors associated with auditory neuropathy/dys-synchrony in a developing country

Two-stage hearing screening, with a first stage of automated otoacoustic emissions (AOAE) followed by automated auditory brainstem response (AABR), is the protocol of choice for the early detection of congenital and early-onset hearing loss (PCEHL) in a number of developed countries. However, this protocol would miss children with auditory neuropathy/ auditory dys-synchrony (AN/AD). The aim of the study was to ascertain the characteristics of infants with AN/AD profile in a developing country and identify predictors of this condition in a primary care, non-hospital-based setting. Case-control analysis of the sociodemographic and medical profile of 11 infants with normal outer hair cell function, but confirmed with PCEHL, were compared to 64 infants with normal hair cell function and no PCEHL. The infants with AN/AD profile were further compared with 45 infants with PCEHL who failed transient evoked otoacoustic emissions (TEOAE). Independent predictors were determined from univariate and multiple logistic regression analyses. Factors associated with AN/AD profile in the univariate analysis were male sex (OR, 9.39: 95% CI 1.1477.74) and hyperbilirubinaemia requiring exchange blood transfusion (OR, 5.63: CI 1.06129.85). About 64% of the infants with AN/AD profile had a history of hyperbilirubinaemia and 54.5% were hospitalized in the first month of life for a serious illness. No independent factor was predictive of AN/AD from multiple logistic regression analysis. Infants with AN/AD profile were significantly more likely to have a history of hyperbilirubinaemia (OR, 14.00: CI 3.00165.34) and be hospitalized in the first month of life (OR, 7.80: CI 1.8033.77) than infants with PCEHL who failed TEOAE. There is no prognostic/selective tool for the early detection of infants with AN/AD profile in non-hospital-based settings in developing countries. AABR screening of infants with normal outer hair cells, who have a history of hyperbilirubinaemia with or without exchange blood transfusion, is recommended as far as practicable, where a two-stage TEOAE/AABR protocol is implemented.

Fluctuating Corticosteroid-Responsive Auditory Neuropathy/Dyssynchrony Is Suggestive of Central Nervous System Pathology

To highlight diagnostic and management features of auditory neuropathy/auditory dyssynchrony (AN/DS) due to central demyelinating disorder. A child with AN/DS due to central nervous system pathologic findings. Audiometry, auditory brainstem response (ABR) test, otoacoustic emission test, magnetic resonance imaging (MRI) with gadolinium contrast, intravenous corticosteroid treatment, antiviral treatment, stereotactic biopsy, and cyclophosphamide immunomodulation. Pure-tone audiometry, speech discrimination testing, ABR, and MRI. A 12-year-old girl presented with acute sensorineural hearing loss, abnormal ABR, and normal otoacoustic emissions consistent with AN/DS. The hearing loss demonstrated fluctuation and corticosteroid responsiveness. Magnetic resonance imaging and stereotactic biopsy revealed brainstem demyelination consistent with multiple sclerosis. Definitive treatment consisted of cyclophosphamide immunomodulation. Although recent focus on pathophysiology of AN/DS has shifted from auditory nerve abnormalities to dyssynchrony within the cochlea, cases associated with fluctuating sensorineural hearing loss and responsiveness to corticosteroid therapy should raise the suspicion of central nervous system pathologic findings. Therefore, it is crucial to obtain brain MRI with contrast enhancement in all patients with AN/DS. This is critical in patients undergoing cochlear implantation because MRI may be contraindicated postoperatively.

Auditory neuropathy/auditory dys-synchrony detected by universal newborn hearing screening

The implementation of neonatal hearing screening has enabled early detection and intervention in hearing loss. The use of otoacoustic emissions (OAE) and auditory brainstem response testing in universal screening has led to the recognition of this recently described disorder called auditory neuropathy/auditory dys-synchrony (AN/AD). This diagnosis indicates that the infant has significant hearing loss despite having normal outer hair cells in the cochlea. We reviewed the characteristics and natural history of nine infants detected to have AN/AD from universal newborn hearing screening in a national pediatric hospital. Fifty-two cases of hearing loss were detected from 14,807 consecutively screened cases. Of the 52 cases, 9 had electrophysiological test results consistent with AN/AD. They include both premature infants who had major neonatal complications and term infants with no perinatal complications. Six cases had bilateral and three cases had unilateral findings. We suggest that AN/AD can occur in low-risk infants and hence screening of high-risk cases alone is insufficient. Our findings are discussed with reference to the current literature.

The Jaundiced Gunn Rat Model of Auditory Neuropathy/Dyssynchrony

High levels of bilirubin are neurotoxic and may result in deafness or auditory neuropathy/auditory dyssynchrony (AN/AD). The jaundiced (jj) Gunn rat animal model of kernicterus has electrophysiologic and neuroanatomic abnormalities of brainstem auditory nuclei with normal cochlear microphonic recordings. We examined morphologic changes in the cochlea, spiral ganglion, and auditory nerve and relate these findings to current understanding of AN/AD. At 15 days of age, jj and nonjaundiced (Nj) littermates were injected with sulfadimethoxine (sulfa) and killed 3 days later by transcardial perfusion. Sections were cut through decalcified temporal bones, cochlear nerves, and auditory brainstem and processed for light and electron microscopy and immunohistochemical localization of calbindin-D and parvalbumin. Spiral ganglion neurons were severely degenerated with a paucity of myelinated axons in jj animals. Electron microscopy of the intramodilar auditory nerve revealed a lack of large caliber axons in jj-sulfa versus Nj-sulfa controls. Large diameter degenerating axons were characterized by an electron-dense atrophied axis cylinder resembling an axonopathy. Our findings of abnormal spiral ganglion cells and selective loss of large, myelinated auditory nerve fibers with no abnormalities in cochlear hair cells, support the sulfa-treated jj Gunn rat as a model for bilirubin induced AN/AD. The paucity of large caliber neurons undermines temporal coding of auditory information and neural synchrony and demonstrates that in addition to brainstem auditory nuclei, spiral ganglion neurons are selectively vulnerable to bilirubin toxicity.

Auditory neuropathy/auditory dys-synchrony in school children with hearing loss: frequency of occurrence

Objective: The frequency of occurrence of a recently identified hearing disorder, auditory neuropathy/auditory dys-synchrony (AN/AD), was investigated in children with hearing impairment in Hong Kong. Methods: In this study, 56 students, aged 7–18 years, attending primary divisions in schools for the hearing impaired were screened using otoacoustic emission procedures. Results: One student in the study group was found to have intact outer hair cell function. A detailed diagnostic assessment of this case strongly suggested AN/AD was involved. Combining the study results with those of a previously conducted survey in Hong Kong, the frequency of occurrence of AN/AD in children attending schools for the hearing impaired was estimated to be 2.44% (3 out of 123 children screened). Estimates of the frequency of occurrence of AN/AD in various other educational settings in Hong Kong were also derived. Conclusions: The study indicates that AN/AD is not an extremely rare disorder. Educational audiologists and other health care professionals need to be actively involved in the identification and management of AN/AD. Research should be directed at technological innovations that may help to overcome the limitations of present screening procedures, in order to more accurately identify the disorder.