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

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

[Auditory neuropathy and prematurity: modern view of the issue (literature review)]. / Auditornaya neiropatiya i nedonoshennost': sovremennyi vzglyad na problemu (obzor literatury).

Auditory neuropathy spectrum disorder (ANSD) is a specific auditory disorder caused by dysfunction of periphery part of the auditory system, in which the function of the outer hair cells is preserved, but the afferent input at the cochlear level suffers due to the pathology of the inner hair cells, neurons of the spiral ganglion and/or the auditory nerve, as well as synaptic contact between them. As a result, a specific condition is formed, in which a patient's otoacoustic emissions and/or cochlear microphonics are present, auditory brainstem responses are abnormal or absent, the discrepancy between the hearing level and the electrophysiological data, poor speech perception which may not correlate with the hearing thresholds. ANSD is a multifactorial disease. One of the main risk factors is perinatal pathology and, in particular, prematurity. The possible factors associated with prematurity that provoke the onset of the disease, features of the pathogenesis, clinical and audiological peculiarities of ANSD in premature infants, contemporary approaches to the habilitation of such patients are discussed in the article. The necessity of an individual, patient-oriented approach to the treatment of premature infants with ANSD is substantiated; such an approach should be based both on the genesis of the disorder, taking into account possible points of lesion in the auditory system, and the developmental peculiarities of a premature baby considering the presence of concomitant diseases associated with prematurity. In the article attention is focused on the main directions of habilitation work with such children, including a multidisciplinary approach, regular careful monitoring of the auditory, speech and language skills, intensive psychological and speech therapist support, the choice of an adequate way of intervention and its improvement as necessary.

[The issue of auditory neuropathy: from origins to the present]. / Problema auditornoi (slukhovoi) neiropatii: ot istokov k sovremennosti.

The issue of auditory neuropathy spectrum disorders (ANSD) has been in a focus of specialists attention for a relatively short time, but during this time a huge amount of scientific and practical knowledge about this hearing disorder has been accumulated. ANSD is a specific auditory deficit caused by dysfunction of periphery part of the auditory system, which may affect the inner hair cells, the spiral ganglion neurons and the auditory nerve, as well as the area of synaptic contact between them, while the outer hair cells, as a rule, remain intact. As a result, a specific condition is formed, in which a patient's otoacoustic emissions and/or cochlear microphonics are present, auditory brainstem responses are abnormal or absent, electrophysiological data may not correlate with hearing level, the discrepancy between pure tone audiometry and speech discrimination is observed. ANSD prevalence, epidemiology, contemporary views on its etiology, including detailed information on hereditary forms of the disorder and its risk factors are considered in the review. The data on the basic rungs of the ANSD pathogenesis, which underlie the development of various forms of the disorder and mainly determine the rehabilitation approach, are presented. The detailed clinical and audiological characteristics of ANSD are presented; contemporary approach to ANSD diagnosis and rehabilitation, including indications for surgical treatment, are considered.

Subcortical deafness as a subtype of auditory agnosia after injury of bilateral auditory radiations caused by two cerebrovascular accidents - normal auditory brainstem responses with I-VII waves and abolished consciousness of hearing.

BACKGROUND: In central auditory disorders caused by damage of the cerebral hemispheres, there are cortical deafness and auditory agnosia. Although clinical cases of cortical deafness have been reported, little is known about the hearing problems and localized lesions associated with cortical deafness. AIMS/OBJECTIVES: The aims of our research are to elucidate lesion sites associated with cortical deafness and to clarify why patients with cerebral lesions are not aware of any sound at all. MATERIALS AND METHODS: Three patients diagnosed as having total loss of hearing participated in this study. We conducted pure-tone audiometry, speech audiometry, distortion product otoacoustic emission (DPOAE), auditory brainstem response (ABR), and brain magnetic resonance imaging (MRI) to diagnose cortical deafness with aphasia tests of these patients. RESULTS: Our studies showed that waves VI and VII as well as waves I to V have normal peak latencies in ABRs in all three patients. In brain MRI, we found complete damage of proximal parts of bilateral auditory radiations in the three patients. CONCLUSIONS: We propose 'subcortical deafness' as a subtype of auditory agnosia.

Alterations of functional connectivity in auditory and sensorimotor neural networks: A case report in a patient with cortical deafness after bilateral putaminal hemorrhagic stroke.

RATIONALE: Cortical deafness is a rare auditory dysfunction caused by damage to brain auditory networks. The aim was to report alterations of functional connectivity in intrinsic auditory, motor, and sensory networks in a cortical deafness patient. PATIENT CONCERNS: A 41-year-old woman suffered a right putaminal hemorrhage. Eight years earlier, she had suffered a left putaminal hemorrhage and had minimal sequelae. She had quadriparesis, imbalance, hypoesthesia, and complete hearing loss. DIAGNOSES: She was diagnosed with cortical deafness. After 6 months, resting-state functional magnetic resonance imaging (rs-fMRI) and diffuse tensor imaging (DTI) were performed. DTI revealed that the acoustic radiation was disrupted while the corticospinal tract and somatosensory track were intact using deterministic tracking methods. Furthermore, the patient showed decreased functional connectivity between auditory and sensorimotor networks. INTERVENTIONS: The patient underwent in-patient stroke rehabilitation therapy for 2 months. OUTCOMES: Gait function and ability for activities of daily living were improved. However, complete hearing impairment persisted in 6 months after bilateral putaminal hemorrhagic stroke. LESSONS: Our case report seems to suggest that functional alterations of spontaneous neuronal activity in auditory and sensorimotor networks are related to motor and sensory impairments in a patient with cortical deafness.

Identification of Perinatal Risk Factors for Auditory Neuropathy Spectrum Disorder.

OBJECTIVES/HYPOTHESIS: To identify medical risk factors associated with auditory neuropathy spectrum disorder (ANSD). STUDY DESIGN: Retrospective case-control study. METHODS: During a 2-year period (2013-2014) patients with newly diagnosed ANSD were identified at a tertiary care facility. Twenty-two patients (n = 22) were identified aged 0.5 to 8.1 years. There were 15 males and seven females. Sixteen had bilateral, four had left-sided, and two had right-sided ANSD. Two age-matched, side-matched, and gender-matched control groups were then collected. The first group was 22 normal-hearing children (n = 22). The second was 22 children with sensorineural hearing loss (SNHL) (n = 22) who did not meet the criteria for ANSD. The chart of each subject was reviewed for the following five-predictor variables: prematurity, low birth weight, jaundice, use of mechanical ventilation, and administration of ototoxic medications. Analysis of variance was performed to analyze the prevalence of perinatal risk factors among the three groups. Multivariate linear regression was then applied. RESULTS: When comparing the ANSD group to both the normal-hearing and SNHL groups, the subjects with ANSD had statistically significant higher rates of prematurity, low birth weight, jaundice, and mechanical ventilation. Multiple regression analysis was performed to identify predictors of ANSD compared to each control group individually. Jaundice in the first month of life approached significance when comparing the ANSD group to the normal-hearing group, and was the only medical risk factor found to be statistically significant when comparing the ANSD group to the SNHL group. CONCLUSIONS: A history of neonatal hyperbilirubinemia was significantly more common in children with ANSD compared to children with severe SNHL. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:671-674, 2021.

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.

Left Ear Hearing Predicts Functional Activity in the Brains of Patients with Alzheimer's Disease Dementia.

OBJECTIVES: To determine whether central speech processing ability, as measured by hearing in noise, differs between right and left ears in adults with Alzheimer's disease related dementia (AD) as well as whether differences in central speech processing ability correlate with an fMRI-based measurement of global functional brain connectivity. METHODS: This prospective study was carried out at a tertiary referral center. Patients with an AD diagnosis and pure tone averages 40 dB HL or better were included. They were examined using resting-state fMRI and underwent central audiometric testing using the Dichotic Sentence Identification Test (DSI), the Dichotic Digits Test (DD), and the Synthetic Sentence Identification Test (SS), which test hearing in noise. DSI scores were correlated with resting-state fMRI connectivity between 361 distinct gray matter brain regions of interest (ROIs). Average global connectivity was calculated as mean functional connectivity between an ROI and the other 360 regions, a quantitative marker representing overall functional connectivity in the brain. RESULTS: Sixteen subjects had adequate fMRI and hearing data. The average age was 71.5 years old (±6.0). The average DSI score for the left ear was 40% (±34%) compared to 90% (±10%) in the right ear (P < .001). No difference between ears was noted on the DD. SS does not differentiate between ears, but worsening scores were noted with increasing background noise. Of the fMRI ROIs, 269 of the 361 had multiple comparison corrected significant correlations between global connectivity and DSI of the left ear (P = .004, r = .673), and all 269 showed higher functional connectivity for individuals with higher left DSI score. No correlations between DSI of the right ear and functional connectivity were found. CONCLUSIONS: Correlation was noted between left sided DSI and functional connectivity in patients with AD. Auditory input from the left ear was more susceptible to impairment, suggesting that side-specific auditory input may influence central auditory processing.

Does riboflavin depletion cause auditory neuropathy spectrum disorder in at risk neonates?

We present a new hypothesis for the pathogenesis of auditory neuropathy spectrum disorder (ANSD) in at risk neonates involving depletion of riboflavin. The association between neonatal hyperbilirubinemia and ANSD is well recognized, yet causation has not been proven. The risk of ANSD does not correlate clearly with severity of hyperbilirubinemia and ASND only occurs in a small proportion of hyperbilirubinemic neonates. Additional, perhaps co-dependent, factors are therefore likely to be involved in pathogenesis. The metabolism of bilirubin consumes riboflavin and levels of riboflavin are depleted further by phototherapy. The neonate may also be deficient in riboflavin secondary to maternal deficiency, and reduced intake or impaired absorption. We propose that riboflavin depletion may be a significant contributor to development of ANSD in at risk neonates. The basis of this hypothesis is the recent recognition that impairment of riboflavin metabolism caused by genetic mutations (SLC52A2 or AIMF1) also causes ANSD.

An integrative approach for pediatric auditory neuropathy spectrum disorders: revisiting etiologies and exploring the prognostic utility of auditory steady-state response.

Auditory neuropathy is an important entity in childhood sensorineural hearing loss. Due to diverse etiologies and clinical features, the management is often challenging. This study used an integrative patient-history, audiologic, genetic, and imaging-based approach to investigate the etiologies and audiologic features of 101 children with auditory neuropathy. Etiologically, 48 (47.5%), 16 (15.8%), 11 (10.9%), and 26 (25.7%) children were categorized as having acquired, genetic, cochlear nerve deficiency-related, and indefinite auditory neuropathy, respectively. The most common causes of acquired and genetic auditory neuropathy were prematurity and OTOF mutations, respectively. Patients with acquired auditory neuropathy presented hearing loss earlier (odds ratio, 10.2; 95% confidence interval, 2.2-47.4), whereas patients with genetic auditory neuropathy had higher presence rate of distortion product otoacoustic emissions (odds ratio, 10.7; 95% confidence interval, 1.3-85.4). In patients with different etiologies or pathological sites, moderate to strong correlations (Pearson's r = 0.51-0.83) were observed between behavioral thresholds and auditory steady-state response thresholds. In conclusion, comprehensive assessments can provide etiological clues in ~75% of the children with auditory neuropathy. Different etiologies are associated with different audiologic features, and auditory steady-state responses might serve as an objective measure for estimating behavioral thresholds.

Cortical deafness of following bilateral temporal lobe stroke.

Cortical deafness is an extremely rare clinical manifestation that originates mainly from bilateral cortical lesions in the primary auditory cortex. Its main clinical manifestation is the bilateral sudden loss of hearing. Diagnosis is difficulty due to its rarity and similarity with other language and communication disorders, such as Wernicke's aphasia, auditory agnosia or verbal deafness. Herein, we present a case report of a young woman with a sudden bilateral loss of auditory comprehension. Initially, a psychiatric nature of the disorder was considered, but the persistence of the symptoms, lead to the diagnosis of cortical deafness secondary to bilateral ischemic lesions in both temporal lobes. Progressive improvement occurred and three months after the initial manifestations she manifested pure verbal deafness. Cortical deafness usually has a poor functional prognosis, with limited therapeutic options. Rehabilitation and speech therapy is recommended to improve the chance of patients achieving communication skills.

Idiopathic Intracranial Hypertension Presenting as Auditory Neuropathy Hearing Disorder in a Child.

Otologic manifestations are known to occur in patients with idiopathic intracranial hypertension (IIH), but the occurrence of sensorineural hearing loss, especially in pediatric populations, has been addressed in only a few reports. Here, we describe a pediatric patient who presented with IIH and severe bilateral hearing loss. The patient's hearing loss was diagnosed as a form of auditory neuropathy (AN) and resolved after prompt treatment of the increased intracranial pressure. This case points to a possible association between IIH and AN and suggests that IIH may potentially be a reversible cause of AN spectrum disorder. Laryngoscope, 129:E407-E411, 2019.

Bridging the brain structure-brain function gap in prosodic speech processing in older adults.

Age-related decline in speech perception may result in difficulties partaking in spoken conversation and potentially lead to social isolation and cognitive decline in older adults. It is therefore important to better understand how age-related differences in neurostructural factors such as cortical thickness (CT) and cortical surface area (CSA) are related to neurophysiological sensitivity to speech cues in younger and older adults. Age-related differences in CT and CSA of bilateral auditory-related areas were extracted using FreeSurfer in younger and older adults with normal peripheral hearing. Behavioral and neurophysiological sensitivity to prosodic speech cues (word stress and fundamental frequency of oscillation) was evaluated using discrimination tasks and a passive oddball paradigm, while EEG was recorded, to quantify mismatch negativity responses. Results revealed (a) higher neural sensitivity (i.e., larger mismatch negativity responses) to word stress in older adults compared to younger adults, suggesting a higher importance of prosodic speech cues in the speech processing of older adults, and (b) lower CT in auditory-related regions in older compared to younger individuals, suggesting neuronal loss associated with aging. Within the older age group, less neuronal loss (i.e., higher CT) in a right auditory-related area (i.e., the supratemporal sulcus) was related to better performance in fundamental frequency discrimination, while higher CSA in left auditory-related areas was associated with higher neural sensitivity toward prosodic speech cues as evident in the mismatch negativity patterns. Overall, our results offer evidence for neurostructural changes in aging that are associated with differences in the extent to which left and right auditory-related areas are involved in speech processing in older adults. We argue that exploring age-related differences in brain structure and function associated with decline in speech perception in older adults may help develop much needed rehabilitation strategies for older adults with central age-related hearing loss.

Pyridoxine Preferentially Induces Auditory Neuropathy Through Mitochondrial Dysfunction and Endoplasmic Reticulum Stress-Mediated Apoptosis.

OBJECTIVES: Auditory neuropathy due to toxicity mechanism of pyridoxine has not yet been fully documented. Therefore, the present study explored a direct mechanism underlying the effects of pyridoxine on auditory neuropathy in organ of Corti (OC) explants ex vivo and cochlear neuroblast cell line, VOT-33 in vitro. METHODS: Primary OC explants containing spiral ganglion neurons and cultured VOT-33 cells were treated with pyridoxine. RESULTS: In nerve fiber of primary OC explants, pyridoxine decreased staining for NF200, a neuro-cytoskeletal protein. We also found that pyridoxine-induced VOT-33 apoptosis, as indicated by accumulation of the sub-G0/G1 fraction, caspase-3 activation, and PARP cleavage. In addition, pyridoxine induced reactive oxygen species (ROS) generation and alteration of mitochondrial membrane potential transition (MPT), including Bcl-2 family protein expression and consequently Ca2+ accumulation and changes of endoplasmic reticulum (ER) stress-related protein expression such as phospho-PERK, caspase-12, Grp78, and CHOP. CONCLUSION: Pyridoxine preferentially induced severe cell death on nerve fiber in primary OC explants and markedly increased apoptotic cell death via mitochondria-mediated ER stress in VOT-33 cells.

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.

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.

The importance of central auditory evaluation in Friedreich's ataxia.

Objective To assess central auditory function in Friedreich's ataxia. Methods A cross-sectional, retrospective study was carried out. Thirty patients underwent the anamnesis, otorhinolaryngology examination, pure tone audiometry, acoustic immittance measures and brainstem auditory evoked potential (BAEP) assessments. Results The observed alterations were: 43.3% in the pure tone audiometry, bilateral in 36.7%; 56.6% in the BAEP test, bilateral in 50%; and 46.6% in the acoustic immittance test. There was a significant difference (p < 0.05) in the comparison between the tests performed. Conclusion In the audiological screening, there was a prevalence of the descending audiometric configuration at the frequency of 4kHz, and absence of the acoustic reflex at the same frequency. In the BAEP test, there was a prevalence of an increase of the latencies in waves I, III and V, and in the intervals of interpeaks I-III, I-V and III-V. In 13.3% of the patients, wave V was absent, and all waves were absent in 3.3% of patients.

The importance of central auditory evaluation in Friedreich's ataxia / A importância da avaliação auditiva central na ataxia de Friedreich

ABSTRACT Objective To assess central auditory function in Friedreich's ataxia. Methods A cross-sectional, retrospective study was carried out. Thirty patients underwent the anamnesis, otorhinolaryngology examination, pure tone audiometry, acoustic immittance measures and brainstem auditory evoked potential (BAEP) assessments. Results The observed alterations were: 43.3% in the pure tone audiometry, bilateral in 36.7%; 56.6% in the BAEP test, bilateral in 50%; and 46.6% in the acoustic immittance test. There was a significant difference (p < 0.05) in the comparison between the tests performed. Conclusion In the audiological screening, there was a prevalence of the descending audiometric configuration at the frequency of 4kHz, and absence of the acoustic reflex at the same frequency. In the BAEP test, there was a prevalence of an increase of the latencies in waves I, III and V, and in the intervals of interpeaks I-III, I-V and III-V. In 13.3% of the patients, wave V was absent, and all waves were absent in 3.3% of patients.

RESUMO Objetivo Avaliar a função auditiva central na ataxia de Friedreich (AFRD). Métodos Foi realizado um estudo retrospectivo de corte transversal. 30 pacientes realizaram anamnese, avaliações otorrinolaringológica, audiológica, imitanciométrica e do potencial evocado auditivo de tronco encefálico (PEATE). Resultados As alterações observadas foram: 43,3% no exame audiométrico sendo 36,7% dos casos, bilateralmente; 56,6% na avaliação do PEATE com 50% dos casos, bilateralmente e 46,6% no exame imitanciométrico. Houve diferença significativa (p < 0,05) na comparação entre os exames realizados. Conclusão No exame audiológico, ocorreu uma preponderância maior da configuração audiométrica descendente a partir da freqüência de 4kHz e ausência do reflexo acústico na mesma frequência. No exame do PEATE, houve prevalência do aumento das latências nas ondas I, III e V, e nos intervalos dos interpicos I-III, I-V e III-V. Em 13,3% dos casos, a onda V estava ausente, e em 3,3% dos casos, todas as ondas estavam ausentes.

Chronic Auditory Toxicity in Late Preterm and Term Infants With Significant Hyperbilirubinemia.

BACKGROUND AND OBJECTIVES: Significant hyperbilirubinemia (SHB) may cause chronic auditory toxicity (auditory neuropathy spectrum disorder and/or sensorineural hearing loss); however, total serum bilirubin (TSB) does not discriminate neonates at risk for auditory toxicity. Our objective was to compare TSB, bilirubin albumin molar ratio (BAMR), and unbound bilirubin (UB) for their association with chronic auditory toxicity in neonates with SHB (TSB ≥20 mg/dL or TSB that met criteria for exchange transfusion). METHODS: Infants ≥34 weeks' gestational age (GA) with SHB during the first 2 postnatal weeks were eligible for a prospective longitudinal study in India. Comprehensive auditory evaluations were performed at 2 to 3 months of age by using auditory brainstem response, tympanometry, and an otoacoustic emission test and at 9 to 12 months of age by using audiometry. The evaluations were performed by an audiologist unaware of the degree of jaundice. RESULTS: A total of 93 out of 100 infants (mean GA of 37.4 weeks; 55 boys, 38 girls) who were enrolled with SHB were evaluated for auditory toxicity. Of those, 12 infants (13%) had auditory toxicity. On regression analysis controlling for covariates, peak UB (but not peak TSB or peak BAMR), was associated with auditory toxicity (odds ratio 2.41; 95% confidence interval: 1.43-4.07; P = .001). There was significant difference in the area under the receiver operating characteristic curves between UB (0.866), TSB (0.775), and BAMR (0.724) for auditory toxicity (P = .03) after controlling for covariates. CONCLUSIONS: Unconjugated hyperbilirubinemia indexed by UB (but not TSB or BAMR) is associated with chronic auditory toxicity in infants ≥34 weeks' GA with SHB.

Auditory dysfunction in patients with Huntington's disease.

OBJECTIVE: Huntington's disease (HD) is an autosomal, dominantly inherited, neurodegenerative disease. The main clinical features are motor impairment, progressive cognitive deterioration and behavioral changes. The aim of our study was to find out whether patients with HD suffer from disorders of the auditory system. METHODS: A group of 17 genetically verified patients (11 males, 6 females) with various stages of HD (examined by UHDRS - motor part and total functional capacity, MMSE for cognitive functions) underwent an audiological examination (high frequency pure tone audiometry, otoacoustic emissions, speech audiometry, speech audiometry in babble noise, auditory brainstem responses). Additionally, 5 patients underwent a more extensive audiological examination, focused on central auditory processing. The results were compared with a group of age-matched healthy volunteers. RESULTS: Our results show that HD patients have physiologic hearing thresholds, otoacoustic emissions and auditory brainstem responses; however, they display a significant decrease in speech understanding, especially under demanding conditions (speech in noise) compared to age-matched controls. Additional auditory tests also show deficits in sound source localization, based on temporal and intensity cues. We also observed a statistically significant correlation between the perception of speech in noise, and motoric and cognitive functions. However, a correlation between genetic predisposition (number of triplets) and function of inner ear was not found. CONCLUSIONS: We conclude that HD negatively influences the function of the central part of the auditory system at cortical and subcortical levels, altering predominantly speech processing and sound source lateralization. SIGNIFICANCE: We have thoroughly characterized auditory pathology in patients with HD that suggests involvement of central auditory and cognitive areas.