Diffusion-Weighted Magnetic Resonance Imaging (dMRI) and Cochlear Implant Outcomes in Axonal Auditory Neuropathy: A Case Report.

BACKGROUND: Progressive auditory dysfunction is common in patients with generalized neurodegenerative conditions, but clinicians currently lack the diagnostic tools to determine the location/degree of the pathology and, hence, to provide appropriate intervention. In this study, we present the white-matter microstructure measurements derived from a novel diffusion-weighted magnetic resonance imaging (dMRI) technique in a patient with axonal auditory neuropathy and consider the findings in relation to the auditory intervention outcomes. METHODS: We tracked the hearing changes in an adolescent with Riboflavin Transporter Deficiency (Type 2), evaluating the sound detection/discrimination, auditory evoked potentials, and both structural- and diffusion-weighted MRI findings over a 3-year period. In addition, we explored the effect of bilateral cochlear implantation in this individual. RESULTS: Between the ages of 15 years and 18 years, the patient showed a complete loss of functional hearing ability. The auditory brainstem response testing indicated an auditory neuropathy with evidence of normal cochlear function but disrupted auditory neural activity. While three structural MRI assessments across this period showed a clinically normal cochleovestibular anatomy, the dMRI evaluation revealed a significant loss of fiber density consistent with axonopathy. The subsequent cochlear implant function was affected with the high levels of current required to elicit auditory sensations and concomitant vestibular and facial nerve stimulation issues. CONCLUSIONS: The case study demonstrates the ability of dMRI technologies to identify the subtle white-matter microstructure changes in the auditory pathway, which may disrupt the neural function in patients with auditory axonopathy.

Outcomes of Cochlear Implant Recipient With ANSD: Intra and Post Operative Findings, Progress in Audition and Speech Skills.

Introduction: Auditory neuropathy spectrum disorder (ANSD) is a distinct type of SNHL that is characterized by the presence of otoacoustic emissions and/or cochlear microphonics. Cochlear implantation was initially not recommended for ANSD children, later studies showed variable outcomes among ANSD. CI is currently the intervention option of choice for many children with ANSD who are unable to obtain benefit from conventional amplification. Aim and Objectives: To review experiences with some of the preoperative and postoperative findings in a child who was diagnosed with auditory neuropathy and provided with cochlear implant. To describe changes in auditory function, which enabled to have significant improvement in hearing and communication skills through auditory verbal therapy (AVT) and regular follow ups. Study Design: Pre and postoperative, findings in cochlear implant recipient who was diagnosed with ANSD. Child received complete medical examinations, including related consultations in audiology, otorhinolaryngology, paediatrics, neurology, psychology, speech language pathology, and radiology. Methodology/Case Report: A 3-year-old-female have brought to the hospital with a C/o not responding to sounds, name call and unable to speak. Medical and Audiological evaluations were initiated. The hearing assessments of the child included appropriate behavioural audiometric techniques, objective measures of middle ear function, acoustic reflex studies, transient evoked (TEOAE), distortion product (DPOAE) otoacoustic emissions and auditory brainstem responses (ABR). Implanted with (HiRes Ultra CI HiFocus SlimJ Electrode), and objective measures were recorded intraoperatively electrode impedances and neural response telemetry (NRT) to assess the outcomes technically. These intraoperative objective measures were used to help program the speech processor for the child. Postoperatively, child has had regular follow-up with otorhinolaryngologist to assure complete healing of the surgical incision, to assess their general medical conditions, and audiologist for switch-on (speech processor) followed by mapping. The hearing and communication skills have been assessed, also continued Auditory Verbal Therapy (AVT) on a regular basis. Postoperatively, objective measures were recorded in regular intervals and monitored with therapy outcomes. Results:  The child has shown significant improvement in sound detection, speech perception abilities, communication skills and shown evidence of progression of good NRT results, which  were recorded and had no postoperative complications. Conclusion:  Experience with cochlear implantation for child diagnosed with ANSD that effectively received and benefited from CI. A detailed and careful evaluations, audiological follow-ups and tailored rehabilitation plans, can be considered as a beneficial management approach for CI, especially who diagnosed with ANSD. The regular use of cochlear implant in this diagnosis can lead to a clear increase in speech comprehension, development and overall progress in quality of life. Success or lack of success with a CI appears to be somewhat dependent on the specific site of lesion (pre- or post-synaptic). Currently there are no clinical measures available to diagnose the specific site of lesion. Indeed, CI appears to be an effective rehabilitation modality for ANSD patients. This may be explained by the fact that the implanted electrode delivers synchronized electrical impulses directly to the auditory nerve, bypassing the presynaptic IHCs and its synapse involved in the unsynchronized firing of the auditory nerve described in ANSD. However, genetic studies that have proven to be essential in the knowledge of underlying mechanisms of ANSD represent a promising therapeutic approach in the management of ANSD.

Auditory Neuropathy Spectrum Disorder in Individuals with Sickle Cell Anemia: Case Study.

The present study attempted to understand the association between Auditory neuropathy spectrum disorder (ANSD) and Sickle cell anemia (SCA) and to recognize possible causative factors for the presence of ANSD in SCA individuals. Two cases, 24 years male and 17years female with a laboratory-confirmed diagnosis of Sickle cell anemia underwent detailed audiological evaluation i.e., pure tone audiometry, speech audiometry, immittance audiometry, otoacoustic emission, and auditory brainstem responses. Audiological evaluation revealed a bilateral moderate low-frequency sensorineural hearing loss in male and bilateral moderately severe sensorineural Hearing loss in female case with elevated Speech Recognition Threshold and poor Speech Identification Scores. 'A' type tympanogram with the absence of Acoustic reflexes and the presence of Otoacoustic emission with no distinct and reproducible peak V in Auditory Brainstem Response (ABR) at 90 dBnHL with the presence of ringing cochlear microphonics on polarity reversal collectively indicating bilateral ANSD in both cases. ANSD and SCA are reported to have a genetic basis of etiology. There might be possibilities that one genetic condition may be common in manifesting both conditions or one genetic condition can cause the presence of another genetic condition or can exaggerate the evolution of another genetic condition. Also, abnormal ABR findings indicate the possibility of neuropathological involvement in isolation or in combination with genetic abnormalities that need detailed investigation to understand non-genetic causative factors. Thus, paved the path for further research in this line and might provide better rehabilitative options.

A novel mutation in the OTOF gene in a Chinese family with auditory neuropathy.

Gene therapy for monogenic auditory neuropathy (AN) has successfully improved hearing function in target gene-deficient mice. Accurate genetic diagnosis can not only clarify the etiology but also accurately locate the lesion site, providing a basis for gene therapy and guiding patient intervention and management strategies. In this study, we collected data from a family with a pair of sisters with prelingual deafness. According to their auditory tests, subject Ⅱ-1 was diagnosed with profound sensorineural hearing loss (SNHL), Ⅱ-2 was diagnosed with AN, Ⅰ-1 was diagnosed with high-frequency SNHL, and Ⅰ-2 had normal hearing. Using whole-exome sequencing (WES), one nonsense mutation, c.4030C>T (p.R1344X), and one missense mutation, c.5000C>A (p.A1667D), in the OTOF (NM_001287489.1) gene were identified in the two siblings. Their parents were heterozygous carriers of c.5000C>A (father) and c.4030C>T (mother). We hypothesized that c.5000C>A is a novel pathogenic mutation. Thus, subject Ⅱ-1 should also be diagnosed with AN caused by OTOF mutations. These findings not only expand the OTOF gene mutation spectrum for AN but also indicate that WES is an effective approach for accurately diagnosing AN.

Childhood fever and hearing loss associated with CAPOS syndrome.

CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) syndrome is a rare genetic disorder caused by the heterozygous mutation, c.2452G > A, in the ATP1A3 gene. CAPOS syndrome involves a characteristic episode in which neuropathy develops after a fever in childhood, and here, we describe the case of a patient with CAPOS syndrome. The patient had repeated episodes of a fever around 74 months of age. Although he could speak at 23 months of age, he presented with hearing difficulty after the fever. Pure-tone audiometry revealed moderate-to-severe bilateral sensorineural hearing loss, and auditory brainstem response (ABR) showed poor response in the both ears. Auditory stead-state response (ASSR) produced relatively consistent results compared to pure-tone audiometry. A mutation in the ATP1A3 gene was detected through genetic testing. In CAPOS syndrome, a genetic mutation leads to desynchronization during neural firing. We believe that this desynchronization in neural firing is responsible for the lack of response in the ABR and the presence of a response in the ASSR. In this patient, we attribute the response detection in ASSR to its greater tolerance for errors in the timing of neural firing compared to ABR.

New Frontiers in Newborn Hearing Screening: Understanding Auditory Neuropathy and its Predictive Trajectory.

Auditory Neuropathy (AN) poses a substantial challenge in neonatal auditory screenings due to its complex course and potential for delayed onset. Early identification and intervention are important for optimizing developmental outcomes. This study aimed to explore the prevalence, determinants, and temporal progression of AN in neonates, and assess the therapeutic benefit of amplification devices on their communication skills. The study utilized a longitudinal cohort design to analyze a cohort of 200 neonates from a tertiary care center over the duration from January 2021 to December 2022. Auditory evaluations were conducted at specified intervals, utilizing a comprehensive battery of auditory assessments. Statistical analyses, including regression models, were employed to identify associations between various determinants and the progression of AN. The results of the study revealed a significant correlation between low birth weight and familial history with onset of AN. The data also revealed a gradual rise in AN prevalence over the study duration. However, a negative correlation was observed between AN severity and communication skills. The utilization of hearing aids was associated with enhanced communication outcomes. The study highlights the importance of comprehensive auditory screenings in newborns, particularly emphasizing the early detection and intervention of AN. Based on empirical findings, it emerged that amplification devices, particularly hearing aids, have the potential to mitigate the detrimental effects of auditory neuropathy (AN) on communication skills. This study provides a valuable contribution to the academic debate by highlighting the need for strengthening neonatal auditory screening protocols. The findings have profound implications for clinical practices, highlighting the role of early interventions in optimizing developmental prospects for neonates diagnosed with AN. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04386-w.

Hearing impairment in systemic sclerosis patients-what do we really know?

Background: Systemic sclerosis (SSc) is a disease of a very heterogeneous clinical picture and immunological profile with progression rate that varies between individuals. Although hearing deterioration is not a complaint that comes to the fore in SSc patients, as it is not life-threatening compared to many other more severe symptoms of this disease, it can significantly impair the quality of life. Medical literature concerning this problem is rather scarce. Materials and methods: In this article we systematically reviewed the medical publications concerning hearing impairment in patients with systemic sclerosis to evaluate current understanding of this complex problem. Following PRISMA guidelines a total of 19 papers were found and analysed including 11 original studies and 8 case reports. Results: Although it seems that hearing impairment in SSc patients is relatively more common than in the general population, based on the analysis of available literature, no firm conclusions regarding its frequency and pathomechanism can be drawn yet. Microangiopathy leading to damage to the sensory cells of the inner ear is suspected to be the main mechanism of hearing loss, although damage to the higher levels of the auditory pathway appears to be underestimated due to incomplete audiological diagnosis. Conclusion: Undoubtedly, the reason for the difficulty in such an evaluation are the complex and still not fully elucidated pathomechanism of SSc, the individually variable dynamics of the disease and the unique heterogeneity of symptoms. Nevertheless, further studies in larger and appropriately selected groups of patients, focused more on the dynamics of microangiopathy and not solely on clinical symptoms could provide answers to many key questions in this regard.

Remediation of Perceptual Deficits in Progressive Auditory Neuropathy: A Case Study.

BACKGROUND: Auditory neuropathy (AN) is a hearing disorder that affects neural activity in the VIIIth cranial nerve and central auditory pathways. Progressive forms have been reported in a number of neurodegenerative diseases and may occur as a result of both the deafferentiation and desynchronisation of neuronal processes. The purpose of this study was to describe changes in auditory function over time in a patient with axonal neuropathy and to explore the effect of auditory intervention. METHODS: We tracked auditory function in a child with progressive AN associated with Charcot-Marie-Tooth (Type 2C) disease, evaluating hearing levels, auditory-evoked potentials, and perceptual abilities over a 3-year period. Furthermore, we explored the effect of auditory intervention on everyday listening and neuroplastic development. RESULTS: While sound detection thresholds remained constant throughout, both electrophysiologic and behavioural evidence suggested auditory neural degeneration over the course of the study. Auditory brainstem response amplitudes were reduced, and perception of auditory timing cues worsened over time. Functional hearing ability (speech perception in noise) also deteriorated through the first 1.5 years of study until the child was fitted with a "remote-microphone" listening device, which subsequently improved binaural processing and restored speech perception ability to normal levels. CONCLUSIONS: Despite the deterioration of auditory neural function consistent with peripheral axonopathy, sustained experience with the remote-microphone listening system appeared to produce neuroplastic changes, which improved the patient's everyday listening ability-even when not wearing the device.

Cochlear implantation in patients with Charcot-Marie-Tooth disease: two cases with a review of the literature.

PURPOSE: To report two cases of bilateral cochlear implantation (CI) in Charcot-Marie-Tooth disease (CMT) patients with novel mutations. Furthermore, we conducted a detailed literature review on the profile and outcomes of CI in this uncommon clinical circumstance. CASE PRESENTATION: Case 1 involved a 25-year-old woman who was referred for sudden hearing loss (HL) in her left ear and had a 7-year history of HL in her right ear. She was diagnosed with CMT type 1 with a thymidine phosphorylase gene mutation. CI was performed on her left side because her hearing gradually worsened to deafness in both ears. At 3 months post-operation, her speech discrimination score without lip-reading improved from 0 to 100%. She underwent a second CI on her right ear 6 months after her first CI. Two years from her first operation, the speech discrimination score was 100%. Case 2 received her first CI on her right ear at the age of nine for her bilateral HL. She was diagnosed with CMT type 2 with a Twinkle mitochondrial DNA helicase gene mutation. Preoperatively, the speech discrimination score in both ear-aided conditions was 70%. At the 7-year post-operation follow-up, the speech discrimination score was 76%. A second CI was performed due to decreasing hearing ability in her left ear. The speech discrimination score showed 100% at 7 months after the second CI. CONCLUSIONS: CI is an effective hearing rehabilitation option for CMT patients with severe-to-profound SNHL. Neuro-otologists should consider CI as a treatment option, even though hearing loss in CMT is associated with auditory neuropathy spectrum disease (ANSD).

AIF translocation into nucleus caused by Aifm1 R450Q mutation: generation and characterization of a mouse model for AUNX1.

Mutations in AIFM1, encoding for apoptosis-inducing factor (AIF), cause AUNX1, an X-linked neurologic disorder with late-onset auditory neuropathy (AN) and peripheral neuropathy. Despite significant research on AIF, there are limited animal models with the disrupted AIFM1 representing the corresponding phenotype of human AUNX1, characterized by late-onset hearing loss and impaired auditory pathways. Here, we generated an Aifm1 p.R450Q knock-in mouse model (KI) based on the human AIFM1 p.R451Q mutation. Hemizygote KI male mice exhibited progressive hearing loss from P30 onward, with greater severity at P60 and stabilization until P210. Additionally, muscle atrophy was observed at P210. These phenotypic changes were accompanied by a gradual reduction in the number of spiral ganglion neuron cells (SGNs) at P30 and ribbons at P60, which coincided with the translocation of AIF into the nucleus starting from P21 and P30, respectively. The SGNs of KI mice at P210 displayed loss of cytomembrane integrity, abnormal nuclear morphology, and dendritic and axonal demyelination. Furthermore, the inner hair cells and myelin sheath displayed abnormal mitochondrial morphology, while fibroblasts from KI mice showed impaired mitochondrial function. In conclusion, we successfully generated a mouse model recapitulating AUNX1. Our findings indicate that disruption of Aifm1 induced the nuclear translocation of AIF, resulting in the impairment in the auditory pathway.

[Distribution characteristics and correlation analysis of GJB2 variation in patients with auditory neuropathy].

Objective:To elucidate the correlation between the GJB2 gene and auditory neuropathy, aiming to provide valuable insights for genetic counseling of affected individuals and their families. Methods:The general information, audiological data（including pure tone audiometry, distorted otoacoustic emission, auditory brainstem response, electrocochlography）, imaging data and genetic test data of 117 auditory neuropathy patients, and the patients with GJB2 gene mutation were screened out for the correlation analysis of auditory neuropathy. Results:Total of 16 patients were found to have GJB2 gene mutations, all of which were pathogenic or likely pathogenic.was Among them, one patient had compound heterozygous variants GJB2[c. 427C>T][c. 358_360del], exhibiting total deafness. One was GJB2[c. 299_300delAT][c. 35_36insG]compound heterozygous variants, the audiological findings were severe hearing loss.The remaining 14 patients with GJB2 gene variants exhibited typical auditory neuropathy. Conclusion:In this study, the relationship between GJB2 gene and auditory neuropathy was preliminarily analyzed,and explained the possible pathogenic mechanism of GJB2 gene variants that may be related to auditory neuropathy.

Cochlear Implantation in Charcot-Marie-Tooth Patients: Speech Perception and Quality of Life.

OBJECTIVES: There is a limited understanding of the impact of cochlear implantation (CI) in patients with Charcot-Marie-Tooth disease (CMT), given the scarcity of reported cases. We aim to evaluate the audiological outcomes and quality of life (QoL) after CI in CMT. METHODS: Multi-institutional, university-affiliated, tertiary-referral centers, retrospective chart review.Our cohort includes 5 patients with CMT. Patients' charts were reviewed for demographic characteristics, operation notes, and pre- and post-implantation audiology evaluation. Patients completed the Cochlear Implant Quality of Life-10 (CIQOL-10) Global questionnaire. RESULTS: Pre-implantation, the mean pure tone average was 84.1 ± 7.2 dB, and the mean word recognition score was 2.4% in the implanted ear. AzBio sentence test was performed in quiet, revealing a mean of 4 ± 1.4% in the implanted ear. Post-implantation, PTA results were all within the mild hearing loss range (mean 33.0 ± 5.9 dB). Post-CI, AZ-Bio test results were 5%, 65%, and 74% (for 3 patients), and HINT scores were 55% and 58% (for 2 patients). The mean score of the CIQOL-10 questionnaire was 42.7 ± 10.47 (range 1-100). Patients were most satisfied with their ability to listen to the television or radio, have conversations in a quiet environment, and feel comfortable being themselves. CONCLUSION: To the best of our knowledge, this is the most extensive series of CI in CMT-associated sensorineural hearing loss and auditory neuropathy. Our cohort suggests that CI is a safe and reliable method for hearing rehabilitation that can achieve good speech performance and improve QoL in CMT patients.

The challenge of a mature final diagnosis of hearing loss severity and early cochlear implantation.

PURPOSE: Despite the recent trend of cochlear implantation (CI) at the age of six or even four months is prevalent in many centers around the world, clinicians should be cautious because perinatal risk factors of auditory neuropathy and/or delayed maturation carry the possibility of reversible hearing loss, yielding better auditory performance at the age of one year. The purpose of this study is to raise awareness that early CI may not be universal for all patients. In addition, we specify the factors to be considered in the pre-operative evaluation of CI in infants younger than one year. METHODS AND RESULTS: This study describes four cases provisionally diagnosed with severe to profound sensorineural hearing loss that were presented to the CI clinic to determine candidacy for implantation. Two cases had histories of prematurity, one had Down syndrome, and one had a family history of hearing loss. None of the study cases were candidates for CI, as they had varying degrees of hearing improvement. CONCLUSION: Although early CI may yield better auditory performance, the final diagnosis should be made only after repeated subjective and objective measurements as well as family feedback on the child's auditory performance, especially in preterm children. Early auditory brainstem response (ABR) prior to the age of one year in children with cognitive, neurologic, or developmental comorbidities should be interpreted with caution, as ABR "alone" could not accurately represent the child's true hearing ability in this patient population.

Preparing for Otoferlin gene therapy trials: A survey of NHS Paediatric Audiology and Cochlear Implant services on diagnosis and management of Auditory Neuropathy Spectrum Disorder.

OBJECTIVES: Gene therapy for monogenic hearing loss is on the horizon. The first trials in patients with Auditory Neuropathy Spectrum Disorder (ANSD) due to pathogenic variants in the Otoferlin (OTOF) gene will open this year. In the UK, the new NHS Genomic Medicine Service (GMS) offers genetic testing in each child diagnosed with congenital or early onset sensorineural hearing loss. This survey study aims to map preexisting clinical pathways for the diagnosis and management of children with ANSD and identify opportunities for improvement in early identification of OTOF- related ANSD. METHODS: A Google form with 24 questions in English covering the ANSD clinical pathway was developed with clinicians involved in the diagnosis and management ANSD. The survey was disseminated via email to all Lead clinicians of NHS Tertiary Paediatric Audiology and Cochlear Implant Services within the UK. RESULTS: Data was received from 27 (34 %) NHS Tertiary Paediatric Audiology Services and 8 (n = 57 %) Paediatric Cochlear Implant Services. Services follow existing national guidance and provide multidisciplinary care with structured patient pathways for referral, diagnosis, and management of children with ANSD and multidisciplinary input throughout. Clinicians are aware of the genetic causes of ANSD and new processes for genetic testing, but do not uniformly refer children with ANSD for testing for OTOF pathogenic variants. As such, they had difficulty estimating numbers of children with OTOF pathogenic variants under their care. CONCLUSION: Those results highlight the urgency of implementing hearing gene panel sequencing for all children with ANSD to provide opportunities for early diagnosis and candidacy for OTOF gene therapy trials.

[Increase in the natural hearing threshold after treatment with cochlear implants]. / Anstieg der natürlichen Hörschwelle nach Cochleaimplantatversorgung.

More than 5% of the world's population suffers from disabling hearing loss. If the cause of hearing loss is unclear, it is referred to as idiopathic sudden sensorineural hearing loss (ISSNHL). After failure of standard treatment, the use of hearing aids or a cochlear implant is generally recommended. In this case, a 55-year-old patient was treated with cochlear implantation (CI) after ISSNHL and unsuccessful conservative therapy. Approximately 1 year after implantation and 7 years after the sudden hearing loss, subjective measurements revealed restoration of the hearing threshold.

Auditory Neuropathy Spectrum Disorder Progressing with Motor and Sensory Neuropathy Caused by an ATP1A1 Variant.

We encountered a 27-year-old Japanese woman with sensorineural deafness progressing to motor and sensory neuropathy. At 16 years old, she had developed weakness in her lower extremities and hearing impairment, which gradually deteriorated. At 22 years old, combined audiological, electrophysiological, and radiological examination results were consistent with auditory neuropathy spectrum disorder (ANSD). Genetic analyses identified a previously reported missense variant in the ATP1A1 gene (NM_000701.8:c.1799C>G, p.Pro600Arg). Although sensorineural deafness has been reported as a clinical manifestation of ATP1A1-related disorders, our case suggested that ANSD may underlie the pathogenesis of deafness in ATP1A1-related disorders. This case report broadens the genotype-phenotype spectrum of ATP1A1-related disorders.

NADH improves AIF dimerization and inhibits apoptosis in iPSCs-derived neurons from patients with auditory neuropathy spectrum disorder.

Auditory neuropathy spectrum disorder (ANSD) is a hearing impairment involving disruptions to inner hair cells (IHCs), ribbon synapses, spiral ganglion neurons (SGNs), and/or the auditory nerve itself. The outcomes of cochlear implants (CI) for ANSD are variable and dependent on the location of lesion sites. Discovering a potential therapeutic agent for ANSD remains an urgent requirement. Here, 293T stable transfection cell lines and patient induced pluripotent stem cells (iPSCs)-derived auditory neurons carrying the apoptosis inducing factor (AIF) p.R422Q variant were used to pursue a therapeutic regent for ANSD. Nicotinamide adenine dinucleotide (NADH) is a main electron donor in the electron transport chain (ETC). In 293T stable transfection cells with the p.R422Q variant, NADH treatment improved AIF dimerization, rescued mitochondrial dysfunctions, and decreased cell apoptosis. The effects of NADH were further confirmed in patient iPSCs-derived neurons. The relative level of AIF dimers was increased to 150.7 % (P = 0.026) from 59.2 % in patient-neurons upon NADH treatment. Such increased AIF dimerization promoted the mitochondrial import of coiled-coil-helix-coiled-coil-helix domain-containing protein 4 (CHCHD4), which further restored mitochondrial functions. Similarly, the content of mitochondrial calcium (mCa2+) was downregulated from 136.7 % to 102.3 % (P = 0.0024) in patient-neurons upon NADH treatment. Such decreased mCa2+ levels inhibited calpain activity, ultimately reducing the percentage of apoptotic cells from 30.5 % to 21.1 % (P = 0.021). We also compared the therapeutic effects of gene correction and NADH treatment on hereditary ANSD. NADH treatment had comparable restorative effects on functions of ANSD patient-specific cells to that of gene correction. Our findings offer evidence of the molecular mechanisms of ANSD and introduce NADH as a potential therapeutic agent for ANSD therapy.

Cochlear implantation in children with auditory neuropathy spectrum disorder: an updated systematic review.

BACKGROUND: The goal of managing auditory neuropathy spectrum disorder (ANSD) is to restore the children's ability to discriminate auditory information. Children who are not making sufficient progress in speech comprehension, and speech and language development after receiving adequate auditory re/habilitation and/or acoustic amplification may be candidates for cochlear implantation (CI). Despite the growing number of published literature on CI outcomes in children with ANSD, the current evidence is primarily based on case reports or retrospective chart reviews some of which had a limited number of children. In addition, the outcomes of CI seem to vary between children with ANSD. Thus, compelling evidence is lacking. This updated systematic review evaluated the speech perception, language, and speech intelligibility outcomes of children with ANSD post-CI. METHODS: An online bibliographic search was conducted in PubMed, Scopus, Web of Science, and CENTRAL databases. We included both interventional and observational studies that assessed the outcomes of the CI in  children with ANSD. RESULTS: Thirty-three studies were included in this systematic review. Several tests were used to assess speech perception following CI in children with ANSD. The findings of this study revealed that  children with ANSD had mean Categories of Auditory Performance scores ranging from 4.3 to 7 post-operatively, this result was better than the pre-operative scores which ranged between 0.4 to 2.5. Likewise, the Infant-Toddler Meaningful Auditory Integration Scale, Phonetically Balanced Kindergarten, and multisyllabic lexical neighborhood test showed clinically relevant improvement after CI. The same findings were reported for language and speech intelligibility scores. One study investigated the quality of life/children satisfaction after CI and showed overall good satisfaction with the outcomes. CONCLUSIONS: The present systematic review suggests that CI is a feasible and effective hearing  rehabilitation modality for children with ANSD. REGISTRATION AND PROTOCOL: PROSPERO ID: CRD42021279140.

Distribution characteristics and correlation analysis of GJB2 variation in patients with auditory neuropathy / 临床耳鼻咽喉头颈外科杂志

Objective:To elucidate the correlation between the GJB2 gene and auditory neuropathy, aiming to provide valuable insights for genetic counseling of affected individuals and their families. Methods:The general information, audiological data（including pure tone audiometry, distorted otoacoustic emission, auditory brainstem response, electrocochlography）, imaging data and genetic test data of 117 auditory neuropathy patients, and the patients with GJB2 gene mutation were screened out for the correlation analysis of auditory neuropathy. Results:Total of 16 patients were found to have GJB2 gene mutations, all of which were pathogenic or likely pathogenic.was Among them, one patient had compound heterozygous variants GJB2[c. 427C>T][c. 358_360del], exhibiting total deafness. One was GJB2[c. 299_300delAT][c. 35_36insG]compound heterozygous variants, the audiological findings were severe hearing loss.The remaining 14 patients with GJB2 gene variants exhibited typical auditory neuropathy. Conclusion:In this study, the relationship between GJB2 gene and auditory neuropathy was preliminarily analyzed,and explained the possible pathogenic mechanism of GJB2 gene variants that may be related to auditory neuropathy.

Comparing Auditory Brain Stem Responses and Transient Otoacoustic Emissions in Premature Infants with Auditory Developmental Delay: Evidence of Temporary Auditory Neuropathy.

Objectives: Premature birth causes some permanent or temporary abnormalities in the hearing system of the newborn. Inadequate development of the central auditory nervous system and balance, as well as the delay in the formation of the nerve myelin, can be the cause of many hearing disorders, including permanent or temporary auditory neuropathy spectrum disorder (ANSD). The present study aims to identify and understand developmental delay disorder in the hearing system of infants and investigate the possibility of temporary auditory neuropathy in infants. Materials & Methods: In this comparative analytical study, twenty premature infants were randomly selected for hearing tests using auditory brainstem response and transient otoacoustic emissions at the time of discharge and three months after the first evaluation. The different components of these tests were analyzed and compared before and after developing the auditory system. Results: The OAEs test showed a signal-to-noise ratio above six dB with appropriate amplitudes in all infants. The grand average waveform of the ABR showed a significant difference between the amplitudes of waves III and V before and after maturation in both ears (p<0.05). In addition, the absolute latency of waves, specifically III and V, showed a significant difference between the two assessment times (0.05). Conclusions: The present study confirmed the occurrence of temporary ANSD or delayed maturation in premature infants following the lack of complete growth and myelination of auditory nerve fibers. There is a need to determine the hearing status of premature infants by frequent examinations and prevent any unnecessary prescription of amplifications.