Auditory neuropathy (AN), auditory neuropathy/dys-synchrony (AN/AD), and auditory neuropathy spectrum disorder (ANSD) are terms used to describe patients, including infants, children and adults, who display auditory characteristics consistent with normal function of portions of the inner ear (normal outer hair cell function) but poor responses from the auditory nerve and brainstem (reflecting inner hair cell, synaptic and/or VIIIth (vestibulo-cochlear) nerve). Patients with AN/AD, based on 10 patients from our clinic and research lab as well as our colleagues, was first described in the modern literature by Starr, Picton, Sininger, Hood and Berlin in 1996 (Starr et al., 1996). A large literature has accumulated worldwide since that time and these patients are believed to comprise approximately 10% of all patients presenting with a severe-profound hearing loss based on auditory brainstem responses (ABR). While patients are seen in most clinical practices, understanding of the characteristics and variation related to AN/AD remains unclear.
Berlin, Hood and Rose (2001) recommended the term auditory dys-synchrony based on two primary underlying reasons. First, the auditory nerve itself may not directly be affected in all cases. The possibility of a sensory rather than neural disorder is based on a number of factors including the lack of a Wave I in the electrocochleogram (ECochG) and the auditory brainstem response (ABR), absence of neuropathy in other than auditory systems, and human and animal temporal bones showing specific inner hair cell loss. Second, the term auditory neuropathy may lead clinicians to discount cochlear implants as a management option even though, as discussed below, cochlear implants have proven beneficial in auditory neuropathy patients. Zeng et al. (1999) showed that patients with auditory neuropathy demonstrate primarily a timing deficit that is consistent with a lack of neural synchrony and Kraus et al. (2000) present a case discussion of evidence for neural asynchrony.
Patients with AN/AD display auditory characteristics consistent with normal outer hair cell function and dys-synchronous responses of the VIIIth (vestibulo-cochlear) nerve. The clinical audiologic tests sensitive to this disorder and useful in correctly identifying patients are physiological measures. Since AN/AD is characterized by normal outer hair cell function and abnormal function in the region of the inner hair cells and/or auditory nerve, the appropriate auditory tests are those sensitive to cochlear and auditory nerve function. Outer hair cell function can be evaluated by measuring otoacoustic emissions (OAEs) and cochlear microphonics. Clinical tests that are specifically sensitive to auditory nerve dysfunction are middle ear muscle reflexes (ipsilateral and contralateral), ABR, masking level difference, efferent suppression of OAEs, and to a limited extent, word recognition with an ipsilateral competing noise or message. Of the above measures, OAEs and the ABR, when used together, offer insight into preneural as well as neural function in the auditory system and thus may form the most sensitive combination.
Patients with AN/AD may or may not have other neurological abnormalities, though many patients have either overt or subtle neuropathies outside of the auditory system. Some patients report symptoms of other non-auditory peripheral neuropathies, while neurologic dysfunction in other patients is revealed only upon clinical neurological examination. Some patients appear to have only an auditory abnormality. Among the neurological abnormalities identified in patients with auditory neuropathy are hereditary sensory-motor neuropathy (HSMN, Charcot-Marie-Tooth Syndrome), Leber’s neuropathy, gait ataxia, loss of deep tendon reflexes, and motor system disturbances. These patients are distinguished from patients with space-occupying lesions, such as VIIIth nerve tumors, or multiple sclerosis. AN/AD is generally bilateral though there are some patients who have been identified with unilateral AN/AD. In an interesting report, Starr et al. (1998) describe three children with a temperature sensitive AN/AD where symptoms only become apparent with elevation of body temperature.
The variability observed in patients continues to suggest several possible mechanisms underlying AN/AD. The characteristics of AN/AD most likely reflect more than a single etiology and thus the disorder(s) may more accurately be described as auditory neuropathies or, as recently suggested, auditory neuropathy spectrum disorder. However, while various etiologies of AN/AD may exist, patients of all ages show a cohesive set of auditory symptoms. The pattern of normal outer hair cell function shown by OAEs and abnormal neural responses shown by the ABR brackets the site of AN/AD to the area including the inner hair cells, the synaptic juncture between the inner hair cells, auditory neurons in the spiral ganglion, the VIIIth nerve fibers, or any combination (Starr et al., 1996; Berlin et al., 1998). Most writers agree with Starr et al. (1991) that the timing problems associated with AN/AD could be sensory, axonic, or dendritic in nature. Possible sites could include the inner hair cells, the synaptic juncture between the inner hair cells and auditory nerve, or the auditory nerve itself. Each of these could result in normal OAEs and a dys-synchronous ABR. There are several sources of information that support the possible involvement of the inner hair cells. The lack of inner hair cells with present outer hair cells demonstrated in animal models such as the Bronx waltzer mouse (Deol and Kocher, 1958) and the Beethoven mouse (Bussoli, Kelly, and Steel, 2001) provide a biological precedence. Recently, this was shown in human infants as well (Amatuzzi et al., 2001) through temporal bone histological studies in infants, providing an important connection to its possible occurrence in humans. In addition, afferent as well as efferent pathways may be involved. The problem might also be related to a biochemical abnormality involving neurotransmitter release. While some insights have been gained into specific sites and mechanisms of AN/AD, much remains to be determined.
Most patients identified who are old enough to provide subjective reports complain first of hearing difficulty in noise (Starr et al., 1996). Patients with AN/AD present a clinical group that requires different management approaches to their auditory and communication problems than approaches used with patients with usual peripheral hearing losses. The effectiveness of amplification is quite variable in persons with AN/AD. A key point in evaluating hearing aid benefit is distinguishing between detection of sound and ability to differentiate (discriminate) among sounds. Cochlear implants have been demonstrated to be beneficial for those patients and families who wish to use auditory information for communication. Much information is needed regarding best management practices and outcomes for patients with AN/AD.
Expected test results in auditory neuropathy/dys-synchrony patients.
Pure tone thresholds:
Normal to severe/profound hearing loss(Any configuration; can be asymmetric)
Speech recognition in quiet:
Variable; slightly reduced to greatly reduced
Middle ear muscle reflexes:
Present (Inverts with stimulus polarity reversal)
Absent (or severely abnormal)
Masking Level Difference (MLD):
No MLD (i.e., 0 dB)
Efferent Suppression of TEOAEs:
Speech recognition in noise:
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Berlin CI, Bordelon J, St. John P, Wilensky D, Hurley A, Kluka E, Hood LJ. 1998. Reversing click polarity may uncover auditory neuropathy in infants. Ear and Hearing 19:37-47.
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Starr A, Sininger Y, Winter M, Derebery MJ, Oba S, Michalewski HJ. 1998. Transient deafness due to temperature-sensitive auditory neuropathy. Ear and Hearing 19:169-179.
Zeng FG, Oba S, Garde S, Sininger Y, Starr A. 1999. Temporal and speech processing deficits in auditory neuropathy. Neuroreport 10:3429-3435.