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.

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.

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.

Predicting the Impact of OTOF Gene Missense Variants on Auditory Neuropathy Spectrum Disorder.

Auditory neuropathy spectrum disorder (ANSD) associated with mutations of the OTOF gene is one of the common types of sensorineural hearing loss of a hereditary nature. Due to its high genetic heterogeneity, ANSD is considered one of the most difficult hearing disorders to diagnose. The dataset from 270 known annotated single amino acid substitutions (SAV) related to ANSD was created. It was used to estimate the accuracy of pathogenicity prediction using the known (from dbNSFP4.4) method and a new one. The new method (ConStruct) for the creation of the protein-centric classification model is based on the use of Random Forest for the analysis of missense variants in exons of the OTOF gene. A system of predictor variables was developed based on the modern understanding of the structure and function of the otoferlin protein and reflecting the location of changes in the tertiary structure of the protein due to mutations in the OTOF gene. The conservation values of nucleotide substitutions in genomes of 100 vertebrates and 30 primates were also used as variables. The average prediction of balanced accuracy and the AUC value calculated by the 5-fold cross-validation procedure were 0.866 and 0.903, respectively. The model shows good results for interpreting data from the targeted sequencing of the OTOF gene and can be implemented as an auxiliary tool for the diagnosis of ANSD in the early stages of ontogenesis. The created model, together with the results of the pathogenicity prediction of SAVs via other known accurate methods, were used for the evaluation of a manually created set of 1302 VUS related to ANSD. Based on the analysis of predicted results, 16 SAVs were selected as the new most probable pathogenic variants.

[Clinical protocol: audiological assessment of infants in Russian Federation. Part II]. / Protokol audiologicheskogo obsledovaniya detei pervogo goda zhizni v Rossiiskoi Federatsii. Chast' II.

This is the second part of the previously published clinical protocol of audiological assessment in infants. The goal of the protocol is unification approaches to audiological diagnosis of the infants. The following sections were included in the second part of the protocol: behavioral testing in infants, testing sequence, duration of the examination and necessity in follow-up, hearing assessment in special cases (premature children, children with congenital infections, after meningitis, with external ear abnormalities, single-sided deafness, with hydrocephalus and shunts, with auditory neuropathy spectrum disorder, with mild hearing loss and otitis media with effusion), medical report.

Expanding Understanding of Electrocochleography in Cochlear Implantation: Auditory Neuropathy Spectrum Disorder With Normal Pure Tone Average.

Objective: Describe the preoperative decision-making, intraoperative electrocochleographic (ECoG) findings, and outcome of cochlear implantation (CI) in a patient with auditory neuropathy spectrum disorder (ANSD) and normal pure-tone thresholds. Patients: A 19-year-old with a history of hypoxic ischemic encephalopathy and seizures was referred for hearing rehabilitation in the setting of typical hearing by pure tone audiometry but poor speech understanding. A diagnosis of ANSD was made based on acoustic brainstem response (ABR), distortion product otoacoustic emission, and acoustic reflex testing. Imaging revealed no central cause of hearing impairment. Interventions: Right-sided CI. Main Outcome Measures: Preoperative and postoperative audiometric data. Intraoperative ECoG. Results: Preoperatively the patient underwent comprehensive audiologic testing with behavioral audiometry, ABR testing, and CI candidacy evaluation. In the right ear, the pure tone average (PTA) was 15 dB and word recognition score was 36%. ABR confirmed ANSD. Preoperative CNC and AzBio in quiet were 8% and 0%, respectively. Intraoperative ECoG amplitudes and audiometry showed responses in the 100 uV range and estimated PTA of 42 dB HL. Postoperative testing at 1-month post-initial activation revealed PTA of 45 dB HL and unchanged word and sentence scores. However, the patient cites an improved ability to communicate and increased confidence and averages over 14 hours of device use daily. Conclusions: To our knowledge, this is the first reported case of CI in an ear with normal PTA. Given that nearly all presently available ECoG data comes from patients with greater degrees of hearing loss, this unique case adds to our understanding of hearing preservation in CI.

Effect of Quiet and Noise on P300 Response in Individuals with Auditory Neuropathy Spectrum Disorder

Abstract Introduction Auditory neuropathy spectrum disorder (ANSD) is a clinical condition in which individuals have normal cochlear responses and abnormal neural responses. There is a lack of evidence in the literature regarding the neural discrimination skill in individuals with ANSD, especially when the signal is presented in the presence of noise. Objectives The present study was performed with the aim to investigate auditory discrimination skill, in quiet and in the presence of noise, in individuals with ANSD and to compare the findings with normal-hearing individuals. Methods A total of 30 individuals with normal hearing sensitivity and 30 individuals with ANSD in the age range of 15 to 55 years old, with the mean age of 27.86 years old, were the participants. P300 response was recorded from both groups using syllable pairs /ba/-/da/ in oddball paradigm and the syllable /da/ in repetitive paradigm in quiet and at +10 dB signal-to-noise ratio (SNR). Results There was significant prolongation in latency and reaction time, and reduction in amplitude of P300 response and sensitivity in both groups with the addition of noise. The topographic pattern analysis showed activation of the central-parietal-occipital region of the brain in individuals with ANSD, whereas activation of the central-parietal region was observed in individuals with normal hearing. The activation was more diffused in individuals with ANSD compared with that of individuals with normal hearing. Conclusion The individuals with ANSD showed a significantly more adverse effect of noise on the neural discrimination skill than the normal counterpart.

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

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

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