The disorder now known as auditory neuropathy (AN) has been defined only within the past 10 years (Starr et al., 1991), although references to patients with this disorder appeared as early as the 1970s and 1980s (Friedman, Schulman, and Weiss, 1975; Ishii and Toriyama, 1977; Worthington and Peters, 1980; Kraus et al., 1984; Jacobson, Means, and Dhib-Jalbut, 1986). This disorder is particularly deleterious when it occurs in childhood because it causes significant disturbance of encoding of temporal features of sound, which severely limits speech perception and, consequently, the development of oral language skills.

Patients with AN have three key characteristics. First, they have a hearing disorder in the form of elevated pure-tone thresholds (which can vary from slight to profound) or significant dysfunction of hearing in noise. Second, they have evidence of good outer hair cell function, in the form of either present otoacoustic emissions or an easily recognized cochlear microphonic component. Third, they have evidence of neural dysfunction at the level of the primary auditory nerve. This condition manifests with an abnormal or absent auditory brainstem response (ABR), beginning with wave I. The presence of hearing dysfunction in quiet, and of poor or absent ABR, distinguish this disorder from central auditory dysfunction, in which hearing and ABR are both normal.

The presence of normal outer hair cell function and the absence of wave I of the ABR narrow the potential sites of lesion in AN to (1) the inner hair cell, (2) the synaptic junction between the inner hair cell and the auditory nerve, and (3) the peripheral portion of the auditory nerve. There is evidence to support the first and third possibilities, but no direct evidence of synaptic disorder.

Starr (2001) has found that approximately one-third of all patients with AN have symptoms of peripheral nerve disease. Approximately 80% of adults with AN demonstrate concomitant peripheral neuropathy, while no patients less than 5 years old show clinical evidence of peripheral nerve disorder. Peripheral neuropathy that was not evident in some of the younger patients emerged in children who were followed over time. In patients with other peripheral nerve involvement, disease of the primary portion of the auditory nerve would be the most parsimonious explanation for the auditory disorder.

More direct evidence of primary auditory nerve disease in humans was reported by Spoendlin (1974) from postmortem temporal bone histologic studies of two sibling adult patients with moderate hearing loss. These individuals had a full complement of inner and outer hair cells but significant loss of spiral ganglion cells. Similar findings were reported by Nadol (2001) in a patient with Charcot-Marie-Tooth syndrome and hearing loss.

Harrison (1999, 2001) has shown that both carboplatin treatment and anoxia can induce isolated inner hair lesions in chinchillas. The same animals had otoacoustic emissions and abnormal ABR results. Amatuzzi et al. (2001) recently reported an autopsy analysis of the temporal bones of three premature infants; findings included isolated inner hair cell loss with a full complement of outer hair cells and auditory neurons. These infants had failed ABR screening while in the neonatal intensive care unit. This study presented the first evidence in humans that an isolated inner hair cell disorder is a possible explanation for AN.

No currently available clinical tools can provide data to distinguish between the inner hair cell and the auditory nerve as site of lesion in AN. Because young children with AN often do not show evidence of other peripheral nerve involvement, it is particularly difficult to know what the underlying pathology of their AN might be. However, it is also not clear how any distinction in pathology could be used to remediate the hearing difficulties in these patients.