International Journal of Pediatric Otorhinolaryngology
Review articleAuditory neuropathy: Endocochlear lesion or temporal processing impairment? Implications for diagnosis and management
Introduction
Hearing provides the pathway through which children normally develop spoken language. It has been demonstrated, however, that speech recognition largely depends on the neural synchrony of auditory perceptions [1], as the latter affects the neural representation of sensory events [2]. Therefore, a desynchronized auditory nerve activity may be accompanied by perceptual consequences, and needs to be timely addressed, in order to ensure a useful language input that could trigger the processes of language acquisition in affected children.
As a clinical entity, auditory neuropathy (also termed auditory dys-synchrony) (AN/AD) is characterized by absent, or grossly abnormal auditory brainstem responses (ABRs), with normal otoacoustic emissions (OAEs) and/or cochlear microphonics (CMs). In addition, word discrimination in these patients is impaired and seems to be disproportional to the pure-tone audiogram [3]. Although this definition is widely accepted in principle, there is still a serious controversy with regard to etiology and management of the AN/AD disorder, with new evidence challenging whatever consensus had been previously achieved.
The aim of the present paper is to review the current knowledge on AN/AD, and to present the therapeutic strategies that can be employed in its management.
Section snippets
Materials and methods
An extensive search of the literature was performed in Medline and other available database sources, establishing two main categories of outcomes:
(a) evaluation of the techniques that have been used in the diagnosis of AN/AD in the pediatric population and (b) assessment of the efficacy of different modalities in the management of AN/AD, taking into account the varying pathologic substrates and related pathophysiologic mechanisms.
Using this framework of results, the retrieved studies were
Results
Seven controlled clinical trials, 17 prospective cohort studies, 14 retrospective cohort studies, seven nested-based case-control studies, nine analytical family studies, three laboratory studies, 18 electrophysiological studies, seven animal models, 19 case-reports, one guideline, one joint statement and 12 review articles met the defined criteria and were included in study selection.
Epidemiology
It was not unusual for most ENT doctors until recently to consider AN/AD a very rare disease, with little (if any) chance to be encountered in their clinical practice. However, current evidence largely supports the opposite—the disease is much more frequent than initially anticipated.
Hence, AN/AD is currently held accountable for as much as 8% of newly diagnosed cases of children with hearing loss per year [6], representing a rather alarming figure, as AN/AD is relatively recently acknowledged,
Conclusion
AN/AD is more frequent than considered in the past, especially amongst hearing-impaired children. Hyperbilirubinemia and hypoxia are major risk factors for this disorder, whereas a genetic substrate involving the OTOF gene is responsible for the AN/AD phenotype in certain cases. Auditory synaptic deficiency, auditory nerve myelinopathy and/or desynchrony of neural discharges are the most probable underlying pathophysiologic mechanisms, causing severe impairment in the patients’ temporal
References (120)
- et al.
“Auditory neuropathy”: physiologic and pathologic evidence calls for more diagnostic specificity
Int. J. Pediatr. Otorhinolaryngol.
(2003) - et al.
Prevalence of auditory neuropathy/synaptopathy in a population of children with profound hearing loss
Int. J. Pediatr. Otorhinolaryngol.
(2006) - et al.
Profound hearing loss and presence of click-evoked otoacoustic emissions in the neonate: a report of two cases
Int. J. Pediatr. Otorhinolaryngol.
(1997) Bilirubin toxicity in the developing nervous system
Pediatr. Neurol.
(2003)- et al.
Transient infantile auditory neuropathy and its clinical implications
Int. J. Pediatr. Otorhinolaryngol.
(2006) - et al.
Results of cochlear implantation in two children with mutations in the OTOF gene
Int. J. Pediatr. Otorhinolaryngol.
(2006) - et al.
Differences in potentials and excitability properties in simulated cases of demyelinating neuropathies, Part I
Clin. Neurophysiol.
(2005) - et al.
Hereditary motor and sensory neuropathy Lom type in an Italian Gypsy family
Neuromuscul. Disord.
(1998) - et al.
Does type I afferent neuron dysfunction reveal itself through lack of efferent suppression?
Hear. Res.
(1993) - et al.
Electrocochleography in auditory neuropathy
Hear. Res.
(2002)
Auditory neuropathy/auditory dys-synchrony detected by universal newborn hearing screening
Int. J. Pediatr. Otorhinolaryngol.
Auditory neuropathy: clinical presentation of seven cases and review of the literature
Ann. Otolaryngol. Chir. Cervicofac.
Temporal and speech processing deficits in auditory neuropathy
Neuroreport
Consequences of neural asynchrony: a case of auditory neuropathy
J. Assoc. Res. Otolaryngol.
Auditory neuropathy
Brain
Clinical guidelines: developing guidelines
BMJ
Pediatric cochlear implantation in auditory neuropathy
Otol. Neurotol.
Clinical findings for a group of infants and young children with auditory neuropathy
Ear Hear.
Auditory neuropathy/dys-synchrony and its perceptual consequences
Trends Amplif.
The varieties of auditory neuropathy
J. Basic Clin. Physiol. Pharmacol.
Risk factors for auditory neuropathy/auditory synaptopathy
ORL J. Otorhinolaryngol. Relat. Spec.
Transient deafness in young candidates for cochlear implants
Audiol. Neurootol.
Newborn hearing screening in the NICU: profile of failed auditory brainstem response/passed otoacoustic emission
Pediatrics
Analyze of the clinical characteristics in children with the severe abnormal auditory brainstem response and normal distortion product otoacoustic emission
Zhonghua Er Bi Yan Hou Ke Za Zhi.
Screening and follow up assessment in three cases of auditory neuropathy
Arch. Dis. Child.
Clinical and audiological features in auditory neuropathy
Arch. Otolaryngol. Head Neck Surg.
Auditory neuropathy: case study with hyperbilirubinemia
J. Am. Acad. Audiol.
Bilirubin and the auditory system
J. Perinatol.
The jaundiced gunn rat model of auditory neuropathy/dyssynchrony
Laryngoscope
Differential vulnerability of inner and outer hair cell systems to chronic mild hypoxia and glutamate ototoxicity: insights into the cause of auditory neuropathy
J. Otolaryngol.
Auditory neuropathy in patients carrying mutations in the otoferlin gene (OTOF)
Hum. Mutat.
Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene
J. Med. Genet.
J. Med. Genet.
Familial auditory neuropathy
Laryngoscope
The genetics of auditory neuropathy
A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness
Nat. Genet.
Cav 1,3 channels are essential for development and presynaptic activity of cochlear inner hair cells
J. Neurosci.
Hair cell synaptic ribbons are essential for synchronous auditory signaling
Nature
Synaptic mechanisms for coding timing in auditory neurons
Annu. Rev. Physiol.
Auditory neuropathy
Lin Chuang Er Bi Yan Hou Ke Za Zhi
An isolated and sporadic auditory neuropathy (auditory nerve disease): report of five patients
J. Laryngol. Otol.
Pathophysiology of auditory neuropathy
Auditory neuropathy in childhood
Laryngoscope
Auditory neuropathy characteristics in children with cochlear nerve deficiency
Ear Hear.
Ten(HL)-test results and psychophysical tuning curves for subjects with auditory neuropathy
Int. J. Audiol.
Auditory processing in individuals with auditory neuropathy
Behav. Brain Funct.
Physiological effects of auditory nerve myelinopathy in chinchillas
Eur. J. Neurosci.
Internodal conduction in undissected demyelinated nerve fibres
J. Physiol.
The effects of experimental demyelination on conduction in the central nervous system
Brain
Transient deafness due to temperature-sensitive auditory neuropathy
Ear Hear.
Cited by (54)
Phrases in noise test (PINT) Brazil: effectiveness of the test in children with hearing loss
2021, Brazilian Journal of OtorhinolaryngologyCitation Excerpt :However, the occurrence of this pathology varies from 0.3% to 1.3% in the population using audiological clinical services, and 12–14% have already been diagnosed with severe to profound hearing loss of cochlear origin.29 Other studies indicate that among children with congenital HI, 2–15% are diagnosed with ANSD, with variable clinical presentations.30–32 In this group, different results were obtained among the participants, which can be explained by the factors that influence the performance of hearing and language skills of children with HI, such as: duration of sensory deprivation, type of device and time of use, family permeability in the therapeutic process and the speech sound coding strategy.
Advances in Management of Pediatric Sensorineural Hearing Loss
2019, Otolaryngologic Clinics of North AmericaRelationship research between auditory neuropathy spectrum disorder and exchange transfusion in neonates with severe hyperbilirubinemia
2019, International Journal of Pediatric OtorhinolaryngologyCitation Excerpt :The incidence of auditory nerve disorder was higher in the phototherapy group and exchange transfusion group than in the NSH group, showing hyperbilirubinemia as a risk factor of auditory nerve disorder. The etiologies of ANSD are diverse, including mainly neonatal hyperbilirubinemia and underlying diseases that cause brain damage [13,14]. Hyperbilirubin, as a common disease in neonatal period, is the most important risk factor for ANSD.
Cochlear implantation in children with auditory neuropathy spectrum disorder: A multicenter study on auditory performance and speech production outcomes
2018, International Journal of Pediatric OtorhinolaryngologyPhotobiomodulation by laser therapy rescued auditory neuropathy induced by ouabain
2016, Neuroscience LettersCitation Excerpt :In recent years, patients diagnosed with auditory neuropathy have been treated at ENT clinics. The hallmark features of AN are normal outer hair cell function and absent/abnormal auditory brainstem responses (ABR) [42]. Unfortunately, there are not any effective therapeutic approaches available for AN, due to its unclear etiology and pathogenesis [34].