Cochlear Implant Outcomes in Patients With TMTC2 -Associated Sensorineural Hearing Loss and Auditory Neuropathy/Auditory Dys-Synchrony.

OBJECTIVE: To investigate the outcomes of cochlear implantation in patients with TMTC2 -associated sensorineural hearing loss and auditory neuropathy/auditory dys-synchrony. PATIENTS: Adult and pediatric cochlear implant (CI) patients followed in an academic center who tested positive for TMTC2 genetic variant rs35725509. INTERVENTION: Cochlear implantation. MAIN OUTCOME MEASURES: Speech perception scores in quiet. RESULTS: Ten CI patients were identified with TMTC2 variant rs35725509 out of 157 patients who underwent genetic testing (i.e., 6.3% of patients tested). All demonstrated progressive, bilateral hearing loss with severe-to-profound audiometric thresholds preoperatively. Pre-CI and 1-year post-CI speech recognition percent correct scores were compared. Post-CI speech perception (mean 61.0%, standard deviation 31.4%) was significantly higher than pre-CI speech perception (mean 21.0%, standard deviation 27.0%) ( p = 0.002). Individually, 9 of the 10 subjects experienced significant improvements in speech perception pre- to post-CI ( p < 0.05). Electrically evoked compound action potential measures were available for five patients, and all showed normal electrically evoked compound action potential thresholds. CONCLUSION: Patients with TMTC2 -associated sensorineural hearing loss and auditory neuropathy/auditory dys-synchrony have significantly improved speech perception outcomes with cochlear implantation and should be considered candidates for this intervention if there are no other contraindications.

[Evaluation of the outcomes of cochlear implant in children with auditory neuropathy].

Objective: To investigate the auditory and speech abilities of children with congenital auditory neuropathy (AN) after cochlear implant (CI), and to analyze the role of genetic testing in predicting the postoperative outcomes of CI in AN patients. Methods: Fourteen children diagnosed with AN by audiological battery test and underwent CI surgery in Xijing Hospital of the Air Force Medical University from 2002 to 2021 were included in this study (9 males and 5 females), with an implantation age of (3.1±1.7) years (mean±standard deviation, the same as follows). The preoperative audiological results and deafness gene results were analyzed. Another 52 children with ordinary sensorineural hearing loss (SNHL) were selected as the control group (30 males and 22 females), with an implantation age of (2.2±0.9) years. The demographic factors such as age and gender were matched with those of the AN group. The modified Category Auditory Performance (CAP-Ⅱ) and Speech Intelligence Rate (SIR) were used to evaluate the development of postoperative auditory and speech abilities in two groups. The Mandarin Speech Test System was used to test the speech recognition rate of monosyllabic and disyllabic words and sentences. Matlab 2022 software was used to analyze the data. Results: The results of gene in 14 children with AN showed that 6 cases had OTOF gene mutations, 2 cases (siblings) were confirmed to have TNN gene mutations through whole exome sequencing, and the remaining 6 cases were not find any clear pathogenic gene mutations. All subjects underwent CI surgery with electrodes implanted into the cochlea smoothly, and there were no postoperative complications. After surgery, all AN children had improved auditory and speech abilities, but only 64% (9/14) of AN children with CI had auditory ability scores comparable to the control group of SNHL children (including 2 children with TNN gene mutations), and 36% (5/14) of AN children had lower scores than the control group of SNHL children.The average speech recognition rate of two children with TNN gene mutations was 86.5%, and of two children with OTOF gene mutations was 83.2%. Conclusions: AN children achieved varying degrees of auditory and speech abilities after CI, but the postoperative effects varied greatly. Some children achieved similar results as ordinary SNHL children, but there were still some children whose effects were worse than those of ordinary SNHL children. The postoperative efficacy of CI in two children with AN caused by TNN pathogenic genes were comparable to that of ordinary SNHL in children. Genetic testing had certain reference value for predicting the postoperative effect of CI in AN children.

Predictors of cochlear implant outcomes in pediatric auditory neuropathy: A matched case-control study.

OBJECTIVES: Current evidence supports the benefits of cochlear implants (CIs) in children with hearing loss, including those with auditory neuropathy spectrum disorder (ANSD). However, there is limited evidence regarding factors that hold predictive value for intervention outcomes. DESIGN: This retrospective case-control study consisted of 66 children with CIs, including 22 with ANSD and 44 with sensorineural hearing loss (SNHL) matched on sex, age, age at CI activation, and the length of follow-up with CIs (1:2 ratio). The case and control groups were compared in the results of five open-set speech perception tests, and a Forward Linear Regression Model was used to identify factors that can predict the post-CI outcomes. RESULTS: There was no significant difference in average scores between the two groups across five outcome measures, ranging from 88.40% to 95.65%. The correlation matrix revealed that younger ages at hearing aid fitting and CI activation positively influenced improvements in speech perception test scores. Furthermore, among the variables incorporated in the regression model, the duration of follow-up with CIs, age at CI activation, and the utilization of two CIs demonstrated prognostic significance for improved post-CI speech perception outcomes. CONCLUSIONS: Children with ANSD can achieve similar open-set speech perception outcomes as children with SNHL. A longer CI follow-up, a lower age at CI activation, and the use of two CIs are predictive for optimal CI outcome.

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.

Audiogram Configuration, Molecular Etiology, and Outcome of Cochlear Implantation in Postlingual Auditory Neuropathy Spectrum Disorder.

OBJECTIVE: To explore the diverse molecular etiologies of postlingual auditory neuropathy spectrum disorder (ANSD) and report on the electrically evoked compound action potential (ECAP) thresholds and the outcome of cochlear implantation (CI). METHODS: Patients with late-onset, progressive hearing loss who went through molecular genetic testing were enrolled. Type of sensorineural hearing loss (SNHL) was classified as flat, reverse-slope, midfrequency, downsloping, or ski slope. We identified postlingual ANSD subjects through diagnostic tracts applied differently depending on the degree of SNHL. For CI recipients, individual ECAP thresholds, postoperative speech perception abilities, and the genetic cause were analyzed. RESULTS: The detection rate of ANSD among patients with postlingual SNHL was 5.1% (15/293 probands). Diverse genetic etiologies were identified in 7 (46.6%) of the 15 postlingual ANSD subjects, the genetic cause being found exclusively in subjects with reverse-slope SNHL. The pattern of intraoperative ECAP responses was also diverse and showed some correlation with the genetic etiology. Despite the diverse molecular etiology and ECAP responses, CI in postlingual ANSD patients, including those with features involving the postsynaptic component, yielded significant improvements in speech understanding. CONCLUSIONS: This study proposes a differentiated diagnostic approach that focuses on both poor speech discrimination and reverse-slope hearing loss for the diagnosis of ANSD. Based on the improvement of speech understanding from all cochlear implantees with ANSD as well as the correlation between the genetic etiology and ECAP thresholds, we suggest that CI can significantly benefit ANSD subjects even those with unknown etiologies unless there is overt peripheral neuropathy.

Results of cochlear implant surgery in patients with auditory neuropathy.

OBJECTIVES: The primary aim of this study was to analyze the benefit of cochlear implants for patients with auditory neuropathy. The secondary aim was to identify risk factors for auditory neuropathy. MATERIALS AND METHODS: Patients with cochlear implants (CIs) who were educated in hearing rehabilitation schools were included in the study. A total of 175 children were operated on for cochlear implantation between August 2019 and August 2021 in the department of otorhinolaryngology at different centers in Turkey, and while 16 (9.1%) of those patients had auditory neuropathy spectrum disorder (ANSD), 159 (90.9%) had sensorineural hearing loss (SNHL). Differences in auditory perception between the two groups were examined. Auditory perception tests were applied for these patients 6 months after CI surgery. The auditory perception performances of the patients were evaluated with the Evaluation of Auditory Responses to Speech (EARS) battery, including the Littlears, Lip, Bis4, Bis12, Cap, Sir, Mtp-3, Mtp-6, Mtp-12, Matrix A1, and Gasp tests. RESULTS: All patients had profound bilateral SNHL. Four auditory perception tests (Littlears, Bis-12, Sir, Matrix A1) showed similar results between patients with ANSD and SNHL, but seven auditory perception tests (Lip, Bis-4, Cap, Mtp-3, Mtp-6, Mtp-12, Gasp) showed significantly higher results among patients with SNHL. Hyperbilirubinemia, prematurity, consanguineous marriage, and family history of hearing loss were found to be common among patients with ANSD. CONCLUSIONS: ANSD patients who do not benefit from hearing aids benefit from CI surgery.

[Electrically evoked ABR through cochlear implant in children with auditory neuropathy spectrum disorder]. / Registratsiya elektricheski vyzvannykh korotkolatentnykh slukhovykh potentsialov u detei s zabolevaniem spektra auditornykh neiropatii.

OBJECTIVE: To estimate the applicability of electrically evoked auditory brainstem response (eABR) registration for the estimation of neural integrity after cochlear implantation (CI) in children with auditory neuropathy spectrum disorder (ANSD) and to compare the eABR data with patient's hearing performance. MATERIAL AND METHODS: 4 children, Nucleus (Cochlear) CI users, with ANSD were enrolled in the study. Hearing performance in these children ranged from successful to unsatisfied. eABR were recorded via Eclipse EP25 (Interacoustics). Electrical bipolar stimulation was achieved with Custom Sound EP software (Cochlear). RESULTS: EABR were registered with the use of different stimulation parameters (pulse width, stimulated electrodes) in 3 patients with satisfactory results of rehabilitation. eABR thresholds corresponded to maximum comfortable levels of patients stimulation MAP. eABR were absent in the patient with poor hearing performance. CONCLUSIONS: EABR measurements in children with ANSD demonstrated restoration of neuronal conduction in the auditory pathway up to the brainstem after cochlear implantation in 3 patients. eABR results were well correlated with hearing performance. Thereby, the study of eABR applicability for clinical practice will be expanded.

Auditory and verbal skills development post-cochlear implantation in Mandarin children with auditory neuropathy: a follow-up study.

BACKGROUND: Cochlear implant (CI) is commonly used as one of the interventions in auditory neuropathy (AN) children. However, there are limited studies regarding the efficiency of CI in AN children. OBJECTIVE: This study aimed to compare the auditory and verbal skills development between the AN and typically developing (TD) children with CI. METHODS: The follow-up study compared the post-CI scores of questionnaires of AN and TD children about auditory and verbal skills development at 0, 1, 2, 3, 6, 9, 12, and 18 months of CI use. RESULTS: The results of auditory perception in AN and TD groups showed a significant improvement after first 3 months. Furthermore, the score was significantly lower in AN group after 18 months of CI use. The results of verbal skills in AN group showed a progressive trend after 9 months of CI use. Besides, the scores were significantly lower in AN group after 12 months of CI use. CONCLUSION AND SIGNIFICANCE: The auditory perception development in AN children with CI was rapidly improved during first 3 months, and verbal skills showed a trend of improvement after 9 months of CI use. However, the differences in auditory and verbal skills between AN and TD groups increased over time.

Resolution of auditory neuropathy spectrum disorder after shunt placement in a patient with hydrocephalus: A case report.

PURPOSE: There have been previous case reports suggesting the resolution of both sensorineural hearing loss and retrocochlear involvement through the management of hydrocephalus with shunt placement. This is a case report of a patient with Auditory Neuropathy Spectrum Disorder (ANSD) that resolved after shunt placement in a patient with hydrocephalus. MATERIALS AND METHODS: Chart review of a single patient with a diagnosis of ANSD and hydrocephalus. Type of audiometric testing and results were document. RESULTS: Patient is an infant who was diagnosed with hydrocephalus at birth and ANSD in the right ear at 3 months of age. Patient underwent shunt placement at 9 months old and had behavioral testing 2 months later. Audiometry showed normal behavioral audiometric thresholds with presence of ipsilateral and contralateral reflexes which is suggestive of resolution of ANSD. CONCLUSIONS: This is a single case report of resolution of ANSD after shunt placement in a patient with hydrocephalus. Close monitoring and repeat audiological evaluation is recommended to follow these patients.

Cochlear Implant Behavioral Outcomes for Children With Auditory Neuropathy Spectrum Disorder: A Mini-Systematic Review.

Objective The aim of this mini-systematic review was to evaluate the evidence reporting speech, language, and auditory behavioral outcome measures for children with a diagnosis of auditory neuropathy spectrum disorder (ANSD) who received cochlear implants (CIs) prior to 3 years of age. Method A mini-systematic review of the literature supporting evidence-based practices was performed. Two databases were searched utilizing a search strategy derived from the PICO (patient, intervention, comparison, outcome) framework. Peer-reviewed articles published between 2009 and 2019 evaluating children with a diagnosis of ANSD who were implanted prior to 3 years of age with a range of speech, language, and auditory behavioral outcomes were included. Four articles meeting inclusion criteria were critically appraised for reputable research design and risks of bias. Each of the four studies was assigned a level of evidence for effectiveness and quality assessment rating. Results Evidence supports cochlear implantation as an appropriate intervention for children with ANSD. Improvements in outcome performance were observed in all the included studies. Children with ANSD fit with CIs can achieve outcomes similar to children with sensorineural hearing loss and CIs, despite the heterogeneity of ANSD. Conclusion These findings have implications for clinical practice and for future research with current CI technology for facilitating parent education, counseling, and realistic expectations for children with ANSD and CIs.

A nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder.

Genes that are primarily expressed in cochlear glia-like supporting cells (GLSs) have not been clearly associated with progressive deafness. Herein, we present a deafness locus mapped to chromosome 3p25.1 and an auditory neuropathy spectrum disorder (ANSD) gene, TMEM43, mainly expressed in GLSs. We identify p.(Arg372Ter) of TMEM43 by linkage analysis and exome sequencing in two large Asian families segregating ANSD, which is characterized by inability to discriminate speech despite preserved sensitivity to sound. The knock-in mouse with the p.(Arg372Ter) variant recapitulates a progressive hearing loss with histological abnormalities in GLSs. Mechanistically, TMEM43 interacts with the Connexin26 and Connexin30 gap junction channels, disrupting the passive conductance current in GLSs in a dominant-negative fashion when the p.(Arg372Ter) variant is introduced. Based on these mechanistic insights, cochlear implant was performed on three subjects, and speech discrimination was successfully restored. Our study highlights a pathological role of cochlear GLSs by identifying a deafness gene and its causal relationship with ANSD.

Cochlear implantation in patient with Charcot-Marie-Tooth disease.

Two patients with auditory neuropathy spectrum disorder (ANSD) considered to be associated with Charcot-Marie-Tooth (CMT) are reported. In case 1, a 23-year-old man presented with progressive bilateral sensorineural hearing loss (SNHL) from 10 years of age and was diagnosed with ANSD. He was later diagnosed with CMT by neurological testing. In case 2, a 16-year-old girl, the younger sister of the patient in case 1, presented with progressive SNHL with similar auditory findings since 6 years of age as those of her brother. Both cases underwent bilateral cochlear implantation. In case 1, the maximum discrimination score improved to 45% 24 months after the first side of cochlear implantation from 5% before the surgery. In case 2, the score was 5% 10 months after cochlear implant (CI) surgery from 0% before the surgery. CI treatment for CMT patients has been considered difficult because of both failure in synchronization of nerve conduction due to demyelination and axonal failure of the auditory nerve. Though slower progress compared to the average subset of patients receiving CI was seen, significant improvement was gradually observed in the present patients after bilateral cochlear implantations. CI is thus a viable option for rehabilitation of SNHL in CMT patients.

EABR measurements during cochlear implantation in one-year-old, infant, child, adult, and elderly patients.

BACKGROUND: Clinical application of electrically-evoked intracochlear auditory brainstem responses (eABRs) for evaluation of brainstem maturity or aging changes has not been well investigated. AIM/OBJECTIVE: We compare the eV latencies of intraoperative eABR measurements in one-year-olds, infants, children, adults, and the elderly, with the goal of investigating the changes in the brainstem auditory pathway due to development and aging. MATERIALS AND METHODS: We studied 58 ears of 51 patients who underwent cochlear implantation between 2013 and 2019 using MED-EL's Concerto or Synchrony implants with Flex28 or Flex soft electrodes. EABRs were recorded during cochlear implantation. The stimuli were delivered by the MED-EL Maestro to the apical, middle, and basal turn electrodes at stimulus levels 1000, 800, and 600 cu, with a pulse width of 30 µs. RESULTS: In eABRs recorded from electrodes installed at both the mastoid and nape, there was no difference in latency between age groups within each stimulus level. CONCLUSION AND SIGNIFICANCE: ABR latency was not affected by development after age one and aging of the brainstem auditory pathway. Our study will be useful as a control in identifying abnormal eABR wave configurations in patients with cochlear malformations, cochlear nerve deficiencies, or auditory neuropathy, regardless of age.

Parents' View on Quality of Life after Cochlear Implantation in Children with Auditory Neuropathy.

OBJECTIVES: The aim of this study is to evaluate the quality of life in pediatric patients with auditory neuropathy according to the perspective of their parents after cochlear implantation. MATERIALS AND METHODS: The pediatric patients, who underwent cochlear implantation with the diagnosis of auditory neuropathy at Izmir Bozyaka Training and Research Hospital ENT Clinic between January 1997 and May 2017, were included to the study. "Parents' Perspective Questionnaire" developed by Nottingham Pediatric Cochlear Implant Programme was used in the study. The questionnaire was composed of 11 subscales and 58 questions in total. RESULTS: The study included 26 pediatric patients (14 female, 12 male) who used cochlear implant for at least 1 year. The mean age of patients was 10.91±3.85 ( 4.3-17.3 years old) and implantation age varied between 14 months and 80 months. (median; 35.65±20.03 months). Patients who attended school had more self-confidence, and also those having implant use over 6 years had a better self confidence and social relationship. CONCLUSION: Cochlear implantation not only improves the ability of hearing but also provides development of speech and language skills and therefore enhancing the patient's quality of life. From the perspective of parents, the use of cochlear implant in the children with auditory neuropathy improves the quality of life in many different ways. The perspective of parents can provide a multidimensional evaluation about the child's progress, therefore, it should be taken into consideration by the staff in implant centers.

Auditory and speech performance in cochlear implanted ANSD children.

BACKGROUND: 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 those subjects. OBJECTIVE: To assess the auditory and speech performance of cochlear implanted children with auditory neuropathy spectrum disorder (ANSD) and to compare these results to those obtained from cochlear implanted children with sensorineural hearing loss (SNHL) Material and methods: 18 cochlear implanted children with ANSD and 40 cochlear implanted children with SNHL were included in this study. Auditory and speech performance results were compared across both subject groups using the Category of Auditory Performance (CAP) and Speech Intelligibility Rate (SIR) tests, with measurements recorded one year post implantation. RESULTS: Cochlear implanted children with ANSD showed clinically significant improvements that were comparable to those observed from cochlear implanted subjects without ANSD. CONCLUSIONS: Children with ANSD benefit from early cochlear implantation and can reach similar auditory and speech performance results as that achieved by children without ANSD.

Taurine enhances mouse cochlear neural stem cell transplantation via the cochlear lateral wall for replacement of degenerated spiral ganglion neurons via sonic hedgehog signaling pathway.

The aim of this paper is to investigate the potential beneficial effects of taurine in cochlear neural stem cell (NSC) transplantation and elucidate the underlying molecular mechanism. The NSC cells were isolated from neonatal Balb/c mice and an auditory neuropathy gerbil model was established by microinjection of ouabain. The spiral ganglion neurons (SGN) were characterized with immunofluorescence stained with Tuj1 antibody. Cell proliferation was determined by BrdU incorporation assay and the morphologic index was measured under the light microscope. The relative protein level was determined by immunoblotting. The hearing of the animal model was scored by click- and tone burst-evoked auditory brainstem response (ABR). Here we consolidated our previous finding that taurine stimulated SGN density and the proliferation index, which were completely abolished by Shh inhibitor, cyclopamine. Transplantation of cochlear NSCs combined with taurine significantly improved ouabain-induced auditory neuropathy in gerbils. In addition, cyclopamine antagonized taurine's effect on glutamatergic and GABAergic neuron population via suppression of VGLUT1 and GAT1 expression. Mechanistically, taurine evidently activated the Sonic HedgeHog pathway and upregulated Shh, Ptc-1, Smo and Gli-1 proteins, which were specifically blockaded by cyclopamine. Here, for the first time demonstrated we that co-administration with taurine significantly improved NSC transplantation and the Shh pathway was identified in this beneficial effect.

The use of animal models to study cell transplantation in neuropathic hearing loss.

Auditory neuropathy (AN) is a form of sensorineural deafness specifically affecting the conduction of the nerve impulse from the cochlear hair cells to the auditory centres of the brain. As such, the condition is a potential clinical target for 'cell replacement therapy', in which a functioning auditory nerve is regenerated by transplanting an appropriated neural progenitor. In this review, we survey the current literature and examine possible experimental models for this condition, with particular reference to their compatibility as suitable hosts for transplantation. The use of exogenous neurotoxic agents such as ouabain or ß-bungarotoxin is discussed, as are ageing and noise-induced synaptopathy models. Lesioning of the nerve by mechanical damage during surgery and the neuropathy resulting from infectious diseases may be very relevant clinically, and we discuss whether there are good models for these situations. We also address genetic models for AN, examining whether the phenotypes truly model the clinical situation in their human counterpart syndromes - we use the example of the hyperbilirubinaemic Gunn rat as a particular instance in this regard.

Cochlear implantation in children with auditory neuropathy: Lessons from Brown-Vialetto-Van Laere syndrome.

OBJECTIVE: Brown-Vialetto-Van Laere syndrome (BVVL) is a rare neurodegenerative disorder associated with auditory neuropathy (AN). The decision process for CI in AN is evolving with increasing evidence of efficacy. We evaluated the benefit of CI in children with BVVL syndrome. METHODS: A retrospective study reviewed the pre- and post-operative hearing outcomes of three patients with BVVL who presented for CI. A fourth patient with BVVL who was not suitable for CI is also discussed. The primary outcomes were hearing thresholds and auditory perception. Outcome measurement instruments included visual reinforcement audiometry (VRA) or Play Audiometry (PA), Categories of Auditory Performance (CAP) and Auditory Speech Sound Evaluation (ASSE). Secondary outcomes were parental report (BAPP questionnaire), the perception of our SaLT and compliance. RESULTS: Patient 1 had ASSE levels of 40-45 dB HL 1 year post-operatively, and CAP score had improved from 2 to 5. At 2-year review, aided thresholds were 40 dB at 2-4 kHz. Three months following CI, the CAP score of Patient 2 had improved from 3 to 5. At 6 months, thresholds were 25-30 dB at 2-4 kHz. Single words/phrases are used by both patients and benefit is reported by both families. Patient 3 has recently undergone CI, having been previously rejected at another centre. Three months following CI, his thresholds were 35-40 dB at 2-4 kHz and increased use of sign and vocalization is reported. CONCLUSION: CI in children with AN complicating BVVL has a variable, but a positive effect. Other manifestations of BVVL make measuring benefit challenging, in the absence of a 'bespoke' measurement instrument for children with complex needs. This study provides further evidence for the benefit of CI in children with AN.

Findings from aetiological investigation of Auditory Neuropathy Spectrum Disorder in children referred to cochlear implant programs.

OBJECTIVES: Auditory neuropathy spectrum disorder (ANSD) is an audiological diagnosis characterised by hearing dysfunction in the presence of intact outer hair cell function in the cochlea. ANSD is thought to account for 7-10% of all childhood permanent hearing impairment, and can result from a range of pathological processes. This paper describes the rationale, methods and findings from the aetiological investigation of ANSD. METHODS: Retrospective audit of four cochlear implant programmes. RESULTS: 97 patients were identified. 79% of patients were identified before the age of one. Prematurity and jaundice were the most frequently identified aetiological factors. 33 patients had cochlear nerve deficiency on imaging. Genetic diagnoses identified included otoferlin, SX010 gene, connexin 26 and A1FM1 gene mutations. ANSD was seen in conjunction with syndromes including Kallman syndrome, CHARGE syndrome, X-linked deafness, SOTOS syndrome, Brown Vieletto Van Laere syndrome, and CAPOS syndrome. DISCUSSION: We present a two-level system of aetiological investigation that is clinically practical. Patients with ANSD sufficiently severe to consider cochlear implantation are generally identified at an early age. Aetiological investigation is important to guide prognosis and identify comorbidity. CONCLUSION: Prematurity and jaundice are the most commonly identified aetiological factors in ANSD. Imaging findings identify crucial factors in a significant minority. An important minority may have genetic and syndromic diagnoses that require further management.