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Mystery Surrounds Auditory Neuropathy Spectrum Disorder

He, Shuman PhD

doi: 10.1097/01.HJ.0000481808.28828.08
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Dr. He is an assistant professor in the Department of Otolaryngology–Head & Neck Surgery at the University of North Carolina at Chapel Hill.

Auditory neuropathy is a form of hearing impairment in which there is normal outer hair cell function. It is indicated by the presence of cochlear microphonics (CMs) and/or otoacoustic emissions (OAE) in conjunction with an aberrant auditory neural system, which is revealed by the absence of, or abnormal, auditory brainstem response (ABR).

About 5 to 10 percent of newly identified hearing loss cases each year present with auditory neuropathy (Rance. Trends Amplif 2005;9[1]:1-43; Vlastarakos. Int J Ped Otorhinolaryngol 2008;72[8]:1135-1150; Berlin. Int J Audiol 2010;49[1]:30-43; Bielecki. Int J Pediatr Otorhinolaryngol 2012;76[11]:1668-1670 Its etiology is not well understood; however, its presence has been linked to several risk factors, including premature birth, neonatal distress (e.g., hyperbilirubinemia, anoxia, artificial ventilation), infection (e.g., mumps, meningitis), neuropathic disorders (e.g., Charcot-Marie-Tooth syndrome, Freidreich's ataxia), genetic factors (e.g., mutations in the otoferlin gene), and ototoxic drugs (e.g., carboplatin). Experts have also reported cases—in non-negligible numbers—with no apparent risk factors or medical comorbidities (Berlin. Int J Audiol 2010;49[1]:30-43; Bielecki. Int J Pediatr Otorhinolaryngol 2012;76[11]:1668-1670; Teagle. Ear Hear. 2010;31[3]:325-335; Roush. Am J Audiol 2011;20[2]:159-170; Pelosi. Otol Neurotol 2012;33[9]:1502-1506

Although the terminology of auditory neuropathy implies a neural site of lesion, this electrophysiological signature might occur in patients with dysfunction of the inner hair cell, inner hair cell–dendrite synapse, the auditory nerve, and its brainstem connections (Buchman. Ear Hear 2006;27[4]:399-408; Rance. Brain 2015;138:3141-3158 The auditory abilities of patients with auditory neuropathy are diverse and, in many cases, poorly understood. Because of the heterogeneity in etiology, site of lesion, and auditory abilities, experts have adopted the term auditory neuropathy spectrum disorder (ANSD) (Guidelines development conference on the identification and management of infants with auditory neuropathy. International Newborn Hearing Screening Conference: Como, Italy. 2008 June 19-21).

Pathophysiological Mechanisms and Functional Hearing Consequences of Auditory Neuropathy

Rance G, Starr A



Rance and Starr provide an excellent review of the current understanding of the underlying pathophysiology of ANSD and its effects on auditory abilities. They point out that both presynaptic and postsynaptic disorders can cause an ANSD phenotype. The presynaptic disorders include inner hair cell dysfunction and/or loss, and deficits in a neurotransmitter release from the inner hair cell–dendrite synapse. The postsynaptic disorders include unmyelinated dendritic nerve terminals dysfunction, axonal neuropathies, auditory ganglion cell disorders, demyelination disorders, auditory nerve hypoplasia, and auditory nerve conduction block.

The authors provide brief, yet precise, summaries for several objective measures commonly used in patients with ANSD: OAE, CM, summating potentials, compound action potentials, ABR, and acoustic middle ear muscle reflex. They point out that objective measures hold great promise for identifying sites of lesion, evaluating treatment outcomes, and proving important information of underlying pathophysiological mechanisms for patients with ANSD. They describe typical patterns of objective measures associated with different pre- and postsynaptic disorders, although they note overlaps in patterns measured for some pre- and postsynaptic disorders.

Rance and Starr summarized the results of studies evaluating auditory abilities in patients with ANSD using psychophysical measures. Studies showed that these patients have deficits in tasks that require perceiving temporal information. They often show impaired understanding of speech, especially in noise. Comparatively, auditory processing of high-frequency and high-intensity information is not affected. Unfortunately, these psychophysical measures cannot distinguish pre- versus postsynaptic neuropathies because both types of disorders affect temporal processing and speech understanding to a similar degree.

Hearing aids (HA) have been used in patients with ANSD who have hearing loss. Improving the signal-to-noise ratio has been approved to be beneficial for these patients. Cochlear implantation (CI) has been used as a treatment option for patients with ANSD who do not benefit from HA. Rance and Starr point out that the CI outcome is closely related to the site(s) of lesion in these patients. For ANSD patients with presynaptic disorders, CI outcomes are comparable with their peers with sensory hearing loss. However, CI outcomes in ANSD patients with postsynaptic disorders show substantial across-patient variations.

Overall, this paper provides a detailed review of our understanding and knowledge in underlying pathophysiology of ANSD and its effects on auditory abilities of patients with this hearing impairment.

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The availability of effective newborn hearing screening programs allows early identification of ANSD. Even though our understanding of ANSD has greatly expanded in the past two decades, many aspects of ANSD remain mysteries. As a result, several major clinical challenges still exist. The first challenge is how to accurately identify sites of lesion for individual ANSD patients who have both pre- and postsynaptic disorders and how to quantify the degree of these disorders. As Rance and Starr pointed out, there are no clinical tools that can be used for these purposes.

The second challenge is how to select appropriate intervention and habilitation strategies for individual patients. HA or CI can benefit many, but not all, patients with ANSD. Whereas some patients receive substantial benefits from their HA (Berlin. Int J Audiol 2010;49[1]:30-43; Deltenre. Audiology 1999;38[4]:187-95; Rance. Ear Hear 1999;20[3]: 238-252; Rance. Ear Hear 2002;23[3]:239-253; Rance. Int J Audiol 2009;48[6]:313-20; Runge. J Am Acad Audiol 2011;22[9]:567-77 or CI (Teagle. Ear Hear. 2010;31[3]:325-335; Breneman. J Am Acad Audiol 2012;23[1]:5-17; Buss. Otol Neurotol 2002; 23[3]:328-32; Dean. Otol Neurotol 2013;34[9]:1610-1614; Johnstone. Int J Audiol 2013;52[6]:400-408; Madden. Otol Neurotol 2002;23[2]:163-168; Mason. Laryngoscope 2003;113[1]:45-49; Shallop. Laryngoscope 2001;111[4 Pt 1]:555-562, other patients fail to show significant improvement in speech perception performance (Berlin. Int J Audiol 2010;49[1]:30-43; Teagle. Ear Hear. 2010;31[3]:325-335; Deltenre. Audiology 1999;38[4]:187-95; Rance. Ear Hear 1999; 20[3]:238-252; Rance. Ear Hear 2002;23[3]:239-253; Goffi-Gomez. Int J Pediatr Otorhinolaryngol 2012;76[2]:257-264; Gibson. Ear Hear 2007;28[2]:102S-106S; Miyamoto. Laryngoscope 1999;109[2]:181-185

To date, there is no robust index of indicators to guide the management of these patients. To further complicate this issue, the auditory brainstem implant (ABI) has been recently used in patients with anatomic cochlear nerve deficiency (CND, the most severe form of neuropathy). There is no overall agreement on whether the ABI is a better intervention strategy than the CI for these patients.

The third challenge is how to optimize fitting and/or programming settings for individual children with ANSD at an early stage. All prescriptive methods used for HA fitting require accurate behavioral threshold inputs to calculate the target gain. Similarly, programming the speech processor of a CI or ABI requires obtaining subjective estimations of the minimum level that patients can detect (T level) and the maximum comfortable level that they can tolerate (C level).

In addition, it is crucial to identify which electrode(s) need to be deactivated due to nonauditory sensation for patients with ABIs. It can be challenging or infeasible to obtain level estimations or descriptions of auditory versus nonauditory sensations in infants and young children. In addition, many children with ANSD have multiple disabilities or medical conditions that limit their abilities to provide reliable behavioral responses, despite advancing age. To date, there is still no reliable clinical tool that can be used to assist in the fitting and/or programming process in these patients. Finally, speech perception skills of children with ANSD show substantial across-patient variations. Underlying mechanisms for these variations are largely unknown. As a result, there is no robust indicator for predicting outcomes of different intervention strategies.

Our understanding of ANSD has been expanded due to vigorous research efforts of several research groups in the world. However, many aspects of ANSD remain mysteries. Further studies about ANSD are warranted.

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