International Journal of Pediatric Otorhinolaryngology
Prevalence of auditory neuropathy/synaptopathy in a population of children with profound hearing loss
Introduction
The term auditory neuropathy (AN) describes a hearing disorder, where a combination of normal otoacoustic emissions (TEOAE) and/or cochlear microphonics (CM) with absent or severely abnormal click-evoked auditory brainstem responses (ABR) at high stimulus levels can be found. The patients with AN present varying pure-tone thresholds ranging from mild to severe uni- or bilateral hearing loss. In quiet they complain a loss of speech comprehension that is out of proportion with their pure-tone hearing thresholds [1]. The term auditory neuropathy was initially defined in 1996 by Starr et al. [2]. He introduced 10 patients where the AN was combined with a general peripheral neuropathy and presumed that the auditory nerve was impaired in a similar way. Nevertheless, other causal mechanisms should be taken into account, resulting in the same conflicting audiological findings. Moreover, Rapin and Gravel [3] discussed these issues in excruciating detail and suggested that the term auditory neuropathy should be restricted to cases in which the locus of pathology is limited to the spiral ganglion cells, their processes or the eighth nerve. The diagnostic term AN is anatomically inappropriate for pathologies from the brainstem to the auditory cortex. The site of lesion could also be localized at the level of the inner hair cells (IHC) as well as the IHC afferent synapse. Recently, a mouse model of auditory neuropathy was described by Khimich et al. [4]. In this mouse mutant for the IHC presynaptic scaffolding protein Bassoon, the lack of active-zone-anchored synaptic ribbons impaired synchronous auditory signalling consistent with “auditory neuropathy”. As long as the specific locus of pathology is not particularly known and an adequate technique to prove the function of the inner hair cells is missing we would favour the expression auditory neuropathy/synaptopathy (AN/AS) to describe patients with normal TEOAE and/or CMs but absent ABR.
The prevalence of AN/AS in children with hearing loss is not precisely known. There are mainly case-studies and small cohorts with 10 or less affected patients with AN/AS described in the literature [2], [5], [6], [7], [8], [9], [10], [11]. However, initial estimates on the prevalence of AN/AS in patients at risk for hearing loss by Davis and Hirsh [12] and Kraus et al. [13] were 0.5% and 1.3%, respectively. They described patients with pure-tone thresholds between normal hearing and moderate hearing loss but absent or abnormal ABR responses and poor speech understanding. Conclusions drawn from these series are limited, as these papers were published well before the TEOAEs were in use and normal TEOAEs or CMs are a precondition of the emerged current AN/AS definition. Furthermore, estimating the occurrence of AN/AS from these studies is difficult as valid results cannot be obtained from studies with small numbers of subjects. Results from studying a large group of 72 patients with AN/AS [14] are restricted to identification of underlying mechanisms, e.g. genetic defects as well as the course of this condition, but predictions about prevalence rates cannot be made.
A systematic Australian study of AN/AS is provided by Rance et al. [15]. This series describes a group of 5199 neonates at risk for hearing impairment, 109 children were found to have elevated ABR-thresholds ≥40 dB nHL and 12 with audiological findings consistent with AN/AS. This data set indicates a prevalence of AN/AS of 11.01% in a population of children with hearing loss, and 0.23% within the at-risk population. However, the value of such surveys is highly dependent on the selection of the participating subjects and needs to be confirmed by other institutions. The presented study provides an insight and discussion of the prevalence of AN/AS in a group of children at-risk for hearing impairment in an urban population in Germany.
Section snippets
Subjects
This retrospective study was performed at the Department of Otolaryngology, Head and Neck surgery at the University of Cologne, Germany (tertiary referral centre). It describes an unselected group of 5190 children with suspicion of hearing loss (Fig. 1, column A). They were either referred to us from children's hospitals or were introduced by ENT-specialists. The infants often show inadequate results in newborn hearing screenings, have risk factors for hearing loss in their medical or family
Results
In the last 8 years, we assessed 5190 children at risk for hearing loss with subjective and objective audiological tests (Fig. 1, column A). In 1775 children assessed with pure-tone audiometry, tympanometry and TEOAE we found no evidence of hearing impairment. Even if these children did not undergo ABR testing, they showed clear and compatible findings in audiological assessment and had no signs to point at AN/AS (Fig. 1, column B). However, we cannot completely rule out an AN/AS in this group
Discussion
With the widespread implementation of otoacoustic emissions in the clinical routine, the early diagnose of AN/AS in children is getting more common. Nevertheless, up to now the prevalence of the disorder has not been precisely defined. The frequency of occurrence of AN/AS is estimated between 0.23% and 1.3% for the at risk clinical population [13], [15] and 11–14.6% in the selected group of patients with severe to profound hearing loss as proofed by absent ABRs [8], [12], [13].
The results of
Acknowledgment
This work was supported by a scholarship of the “Novartis-Stiftung für therapeutische Forschung” to Dirk Beutner.
References (30)
- et al.
Auditory neuropathy: physiologic and pathologic evidence calls for more diagnostic specificity
Int. J. Pediatr. Otorhinolaryngol.
(2003) - et al.
Auditory neuropathy: a report on three cases with early onsets and major neonatal illnesses
Electroencephalogr. Clin. Neurophysiol.
(1997) - 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) - et al.
Does type I afferent neuron dysfunction reveal itself through lack of efferent suppression?
Hear. Res.
(1993) - et al.
Patients with auditory neuropathy: who are they and what can they hear?
- et al.
Auditory neuropathy
Brain
(1996) - et al.
Hair cell synaptic ribbons are essential for synchronous auditory signalling
Nature
(2005) - et al.
Brainstem abnormalities in neonates with normal otoacoustic emissions
Semin. Hearing
(1996) - et al.
Reversing click polarity may uncover auditory neuropathy in infants
Ear Hear.
(1998) - et al.
Auditory neuropathy in childhood
Laryngoscope
(1998)
Audiologic evaluation of neonates with severe hyperbilirubinemia using transiently evoked otoacoustic emissions and auditory brainstem responses
Laryngoscope
Subjective deafness in case of peri-synaptic audiopathy. Isolated defects of the inner haircells?
Laryngorhinootologie
A slow brain stem response for low-frequency audiometry
Audiology
Absent auditory brain stem response: peripheral hearing loss or brain stem dysfunction?
Laryngoscope
A dominantly inherited progressive deafness affecting distal auditory nerve and hair cells
J. Assoc. Res. Otolaryngol.
Cited by (86)
Advances in endoscopic visualization and surgical navigation
2023, Cerebrospinal Fluid Rhinorrhea: Comprehensive Guide to Evaluation and ManagementTask force Guideline of Brazilian Society of Otology ‒ hearing loss in children – Part I ‒ Evaluation
2023, Brazilian Journal of OtorhinolaryngologyMutations in LOXHD1 gene can cause auditory neuropathy spectrum disorder
2021, Otolaryngology Case ReportsCry features of healthy neonates who passed their newborn hearing screening vs. those who did not
2021, International Journal of Pediatric OtorhinolaryngologyCitation Excerpt :In many countries, routine newborn-hearing screening (NHS) is part of a basic neonatological assessment. Since auditory neuropathy spectrum disorders (prevalence 5–19% [4–6]) cannot be identified by OAE screening, the ABR technique represents the current clinical gold standard [7]. Several reports [8–11] suggest that the reliability of this screening is high (specificity of 97,9%; sensitivity 100%).
Auditory neuropathies in children: Clinical features and audiometric assessment
2021, Journal de Pediatrie et de PuericultureLong-term treatment outcomes in children with auditory neuropathy spectrum disorder (ANSD)
2020, International Journal of Pediatric Otorhinolaryngology