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.

Auditory neuropathy in late preterm infants treated with phototherapy for hyperbilirubinemia.

OBJECTIVE: To evaluate the prevalence of auditory neuropathy (AN) in late preterms treated with phototherapy for hyperbilirubinemia. DESIGN: Prospective observational study comprising late preterms treated with phototherapy for hyperbilirubinemia. Newborns were screened with combined transient-evoked otoacoustic emissions (TEOAEs) / automated auditory brainstem responses (AABR). Infants who failed screening underwent diagnostic (ABR). Infants were all re-evaluated with AABR at one year. STUDY SAMPLE: Eighty-five infants with a mean serum total bilirubin concentration of 22.3 ± 1.76 mg/dl; severe-hyperbilirubinemia (SH), and 102 infants with a mean serum total bilirubin concentration of 18.6 ± 1.26 mg/dl; non-severe hyperbilirubinemia (NSH) were included. RESULTS: From 85 late preterms with SH, six (7.1%) failed screening and underwent diagnostic ABR for six weeks. AN was diagnosed in two (2%) infants with SH. Four (3.9%) of the 102 controls with NSH demonstrated failure at TEOAE/AABR. No AN was diagnosed in the control group at the diagnostic ABR. No statistically significant difference was found between infants treated with phototherapy for SH and NSH with regard to AN/AD either in the postnatal period or at one year. No correlation was found between serum bilirubin levels and ABR latencies or thresholds. CONCLUSIONS: AN (2%) in late preterms treated with phototherapy for severe-hyperbilirubinemia was not higher than in those with non-severe hyperbilirubinemia.

Auditory neuropathy in individuals with Type 1 diabetes.

Peripheral neuropathy is a major consequence of diabetes mellitus with up to 50 % of patients showing clinically significant neural injury during the disease course. Hearing loss (as defined by impaired sound detection thresholds) is a recognized symptom of DM, but the possibility of auditory neuropathy (AN) has not been explored in this population. This pilot study investigated peripheral auditory function, auditory processing and speech perception in individuals with Type 1 diabetes mellitus (T1DM) and compared the findings with measures of vestibular function, ocular pathology/visual acuity and overall neurologic profile. Ten adults with T1DM and ten matched controls underwent a battery of tests which included: audiometry, otoacoustic emissions, auditory brainstem responses, temporal processing measures and speech perception. Six of the ten T1DM participants showed electrophysiologic evidence of AN and impaired functional hearing. Furthermore, auditory capacity was correlated with both visual acuity and degree of somatic peripheral neuropathy. This pilot investigation revealed functional-hearing deficits severe enough to impact upon everyday communication. Should the findings be confirmed by larger studies, auditory evaluation may form an important part of the management regimen for individuals with T1DM. This may be especially important for those with DM-related eye conditions, as deficits across multiple sensory modalities can have multiplicative detrimental effects on quality-of-life.

Auditory system dysfunction due to infantile thiamine deficiency: long-term auditory sequelae.

Eleven infants who were fed a thiamine-deficient formula for a mean of 3 months were evaluated for immediate and long-term auditory abnormalities. At presentation, 8 infants had auditory neuropathy spectrum disorder (ANSD), which resolved with supplementary thiamine in 5 children, was permanent in 2 children, and deteriorated in 1 patient who died at the age of 7 years. An additional patient had an auditory pattern corresponding to that of auditory neuropathy of brain stem origin. The 2 remaining patients had unilateral cochlear hearing loss. Six to 8 years later, all patients with transient ANSD had normal audiograms, 2 patients had unilateral cochlear hearing loss, and the rest had neural hearing loss. All survivors had a language developmental delay and impaired speech intelligibility of varying degrees, especially in the presence of background noise. Thiamine is crucial for normal auditory development and function, and its deficiency may be considered an acquired metabolic cause of ANSD in infants.

Auditory function in individuals within Leber's hereditary optic neuropathy pedigrees.

The aims of this study are to investigate whether auditory dysfunction is part of the spectrum of neurological abnormalities associated with Leber's hereditary optic neuropathy (LHON) and to determine the perceptual consequences of auditory neuropathy (AN) in affected listeners. Forty-eight subjects confirmed by genetic testing as having one of four mitochondrial mutations associated with LHON (mt11778, mtDNA14484, mtDNA14482 and mtDNA3460) participated. Thirty-two of these had lost vision, and 16 were asymptomatic at the point of data collection. While the majority of individuals showed normal sound detection, >25% (of both symptomatic and asymptomatic participants) showed electrophysiological evidence of AN with either absent or severely delayed auditory brainstem potentials. Abnormalities were observed for each of the mutations, but subjects with the mtDNA11778 type were the most affected. Auditory perception was also abnormal in both symptomatic and asymptomatic subjects, with >20% of cases showing impaired detection of auditory temporal (timing) cues and >30% showing abnormal speech perception both in quiet and in the presence of background noise. The findings of this study indicate that a relatively high proportion of individuals with the LHON genetic profile may suffer functional hearing difficulties due to neural abnormality in the central auditory pathways.

Hearing status in neonatal hyperbilirubinemia by auditory brain stem evoked response and transient evoked otoacoustic emission.

Hyperbilirubinemia at neonatal period is one of the major deteriorating factors of the auditory system. If left untreated, it may cause certain cerebral damage. This study aims to evaluate the impact of hyperbilirubinemia on the hearing of neonate. This study was conducted on 35 newborn babies with jaundice (bilirubin more than 20 mg/dL). Auditory brainstem response (ABR) and transient evoked otoacoustic emission (TEOAE) tests were performed, after treatment and one year after. ABR test results indicated that 26 children (74.3%) had normal hearing but 9 (25.7%) suffered from an impairment. As for TEOAE test, 30 children (85.7%) passed whereas the remaining (14.3%) seemed to be failures. The comparative results of the two tests pointed to autonomic neuropathy /autonomic dysreflexia symptoms in 5 babies. Due to the high incidence of autonomic neuropathy/autonomic dysreflexia among hyperbilirubinemic babies, screening in this regard seems reasonable. Our result emphasizes the necessity of more experiments on the afflicted areas.

Risk factors for auditory neuropathy spectrum disorder in NICU infants compared to normal-hearing NICU controls.

OBJECTIVES: To evaluate independent etiologic factors associated with auditory neuropathy spectrum disorder (ANSD) in infants who have been admitted to the neonatal intensive care unit (NICU) compared to normal-hearing controls. STUDY DESIGN: Case-control study. METHODS: We included all infants (n = 9) with the ANSD profile admitted to the NICU of Sophia Children's Hospital between 2004 and 2009. Each patient was matched with four normal-hearing controls of the same gender and postconceptional age. The following possible risk factors were studied: birth weight, dysmorphic features, APGAR scores (at 1, 5, and 10 minutes), respiratory distress (IRDS), cytomegalovirus (CMV) infection, sepsis, meningitis, cerebral bleeding, hyperbilirubinemia requiring phototherapy, peak total bilirubin level, furosemide, dexamethason, vancomycin, gentamycin, and tobramycin administration. RESULTS: Nine infants met the ANSD criteria in one or both ears. IRDS (P = .02), meningitis (P = .04), and vancomycin administration (P = .009) were significantly increased in infants with ANSD compared to controls. CONCLUSIONS: In high-risk NICU infants IRDS, meningitis and vancomycin administration are associated with auditory neuropathy spectrum disorder.

Disturbance of automatic auditory change detection in dementia associated with Parkinson's disease: A mismatch negativity study.

OBJECTIVE: To investigate whether automatic auditory change detection, as measured by the mismatch negativity (MMN) event-related potential waveform, differs in dementia associated with Parkinson's disease (PDD) and dementia with Lewy-bodies (DLB) as compared to Alzheimer's disease (AD), Parkinson's disease without dementia (PD) and healthy control subjects (HC). METHOD: Seventeen DLB, 15 PDD, 16 PD, 16 AD patients and 18 HC subjects participated. A passive MMN event-related potential paradigm and an oddball-distractor reaction time paradigm were presented. RESULTS: The PDD patients had reduced MMN area and amplitude compared to the DLB, PD, and the HC groups. The MMN area correlated significantly with number of missed target stimuli in the oddball-distractor task, and the PDD group missed targets significantly more often than the DLB group. CONCLUSION: The results indicate that PDD patients to a larger degree than patients with DLB have a deficit of automatic auditory change detection that contributes to impairment in their ability to selectively attend and respond to deviant auditory stimuli.

Brainstem electronic implants for bilateral anacusis following surgical removal of cerebello pontine angle lesions.

The multichannel auditory brainstem implant (ABI) has been used successfully to treat deafness in individuals with neurofibromatosis type II. The device has been implanted in nearly 150 recipients worldwide, and clinical trials with the device are approaching completion. The implantation and fitting of the multichannel ABI differ significantly from cochlear implantation, and the processes are illustrated in a series of case studies. Performance data also are included from recipients with up to 7 years experience.

[Comparative analysis on the hearing ability of children in iodine deficiency areas born before and after iodine supplementation].

UNLABELLED: According to the detection of hearings ability of children in iodine deficiency areas who was born before and after iodine supplement, the effects of iodine supplement on hearing system development was evaluated. METHOD: Hearing was tested by AS-72 type pure zone diagnostic audiometer(made in Denmark). Hearing of 11-14 years old students were tested before iodine supplement in iodine deficiency areas in 1984, the control was students living in non-iodine deficiency areas. Iodine salt (50 mg/kg) were supplied by the end of 1984, the hearings of children born after one year of iodine supplied were tested in 1999. The result showed that the average hearing threshold of students before iodine supplied in iodine deficiency areas was significance higher than of non-iodine deficiency areas. The hearing of children born after one year of iodine salt supplied in deficient areas had no significant difference from that of normal areas. The development of hearing system might be deteriorated by iodine deficiency during pregnant. It was able to meet the need of iodine that pregnant women ate 1:20 thousands iodine salt.

The neural correlates of 'deaf-hearing' in man: conscious sensory awareness enabled by attentional modulation.

Attentional modulation of normal sensory processing has a two-fold impact on human brain activity: activation of a network of localized brain regions is associated with paying attention, and activation of specific sensory regions is enhanced relative to passive stimulation. The mechanisms underlying attentional modulation of perception in patients with lesions of sensory cortices are less well understood. Here we report a unique patient suffering from extensive bilateral destruction of the auditory cortices (including the primary auditory fields) who demonstrated conscious perception of the onset and offset of sounds only when selectively attending to the auditory modality. This is the first description of such an attentively modulated 'deaf-hearing' phenomenon and its neural correlates, using H(2)(15)O-PET. Increases in cerebral blood flow associated with conscious awareness of sound that was achieved by listening attentively (compared with identical auditory stimulation presented when the patient was inattentive) were found bilaterally in the lateral (pre)frontal cortices, the spared middle temporal cortices and the cerebellar hemispheres. We conclude that conscious awareness of sounds may be achieved in the absence of the primary auditory cortex, and that selective, 'top-down' attention, associated with prefrontal systems, exerts a crucial modulatory effect on auditory perception within the remaining auditory system.

Stimulation of the cochlear nucleus with multichannel auditory brainstem implants and long-term results: Freiburg patients.

Since 1992 18 patients with bilateral retrocochlear deafness have been provided with a multichannel auditory brainstem implant (ABI). The surgical procedure implies tumour removal and ABI implantation in one stage. Most implantations were via the translabyrinthine approach. The long-term follow-up varied between nine and 80 months. In one case auditory perception could not be achieved and in a second case post-operative stimulation was not possible as the subject died due to lung emboli. In all the other cases auditory perception was achieved and only two subjects became non-users during the follow-up period. The presented long-term results suggest that deaf neurofibromatosis type 2 patients regain acoustic contact with the environment, enlarge their communication skills and improve their quality of life by using a multichannel auditory brainstem prosthesis.

A distinct low-level mechanism for interaural timing analysis in human hearing.

The detection of phase or timing differences, and amplitude differences between the two ears are cues for the spatial analysis of sound by humans. Previous physiological and anatomical studies of animals suggest that phase and amplitude differences between the ears may depend on different pathways, though human psychophysical studies suggest that interaural phase and amplitude differences between the two ears may be coded in the same way. Here we describe detailed psychophysical analysis of a subject with multiple sclerosis affecting the brain stem. He has a complete deficit in the detection of phase between the ears with preserved detection of interaural amplitude. The results prove that a distinct mechanism exists in humans for interaural phase detection.