Auditory Neuropathy

The term auditory neuropathy/auditory dyssynchrony (AN/AD) describes a diagnosis that affects a small group of patients with hearing loss and speech intelligibility scores out of proportion with their presumed hearing loss. Many authors have suggested that the abnormalities that cause AN/AD reside within the lower auditory system. Specifically, the spiral ganglion cells, auditory nerve, and auditory brainstem nuclei have all been implicated. The combination of a dysfunctional auditory nerve with preservation of cochlear function can theoretically be caused at several different points along the lower auditory pathway. The following abnormalities have been proposed:

• Injury to the synaptic junction between inner hair cells of the cochlea and dendrites of spiral ganglion neurons

• Direct damage to the dendrites of the spiral ganglion neurons

• Direct injury to the spiral ganglion neurons

• Direct axonal damage to the auditory nerve that causes a cascade of damage to the lower auditory nuclei

A study by Cooper et al indicated that structural brain differences exist between children with AN/AD and healthy controls. The cortical thickness of the right temporal lobe was found to be reduced in children with AN/AD. Moreover, the subjects with AN/AD had significantly greater mean diffusivity in the corpus callosum and right occipital white matter, as determined using diffusion tensor imaging. This diffusivity change may be evidence for density loss in  the white matter microstructure of youngsters with AN/AD.[4]

Several risk factors have been speculated to contribute to AN/AD, including the following[5] :

• Neonatal history of anoxia;

• Neonatal history of hyperbilirubinemia;

• Neonatal history of mechanical ventilation, hypoxia, or both;

• Congenital brain abnormalities;

• Low birth weight

• Extremely premature birth (< 28 wk);

• Genetics or family history of AN/AD

In addition, AN/AD has been reported in association with viral diseases, seizure disorders, and high fever.

AN/AD can occur with or without accompanying neurologic disorders. Friedrich ataxia, Stevens-Johnson syndrome, Ehlers-Danlos syndrome, and Charcot-Marie-Tooth syndrome are all disorders with peripheral neuropathies that have been associated with AN/AD. Although a complicated perinatal history is common among most patients with AN/AD, one third of patients have no predisposing factors that led to the development of AN/AD.

A study by Kitao et al suggested that adults with AN/AD have a higher rate of decrease in distortion product otoacoustic emissions (DPOAEs) than do pediatric patients with the disease (72% of ears vs 45% of ears, respectively), but a lower rate of DPOAE loss (6% of ears vs 27% of ears, respectively).[6]

A study by Apeksha and Kumar reported that compared with persons with normal hearing, patients with AN/AD spectrum disorder have more diffuse brain activations in response to detection and discrimination of speech sounds. The investigators also found evidence, through behavioral data, that sensitivity is lower and reaction times are longer when these patients are exposed to oddball stimuli.[7]

Current research is aimed at the development of animal models to help decipher the exact etiology of AN/AD. Several attempts have been made to replicate the electrophysiologic findings of normal OAEs and abnormal ABRs in an animal model for AN. The first was a chinchilla model that used carboplatin ototoxicity. In this model, intravenous carboplatin treatment produces a selective, although variable, loss of inner hair cells. This animal model displayed the electrophysiologic correlate of normal OAEs and cochlear microphonics (CMs) but elevated thresholds of the ABRs.

However, the magnitude of inner hair cell loss (>50% at the apex of the cochlea and a higher percentage at the base) in this animal model indicates that if inner hair cell loss due to cochlear hypoxia were a significant factor in accounting for the paradoxical finding of normal OAEs and absent or abnormal ABRs, pure tone thresholds would be considerably more elevated than is consistent with the normal to moderate hearing loss characteristic of most patients with AN.

In another model, chronic infusion of ouabain to the round window of gerbils has also shown some physiological similarities to the findings associated with AN/AD and has the potential to be an animal model for AN/AD. This animal model shows the direct destruction of the spiral ganglion cells and produces the same constellation of symptoms found in humans with AN/AD. Although the diagnostic testing results were similar to those found in patients with AN/AD, the destruction of spiral ganglion cells may not be representative of the true pathology of AN/AD.

Another emerging animal model is the Gunn rat. This mutant of the Wistar rat is a well-known animal model for hyperbilirubinemia. Early studies have shown preservation of the CMs with severely abnormal ABRs. Immunohistochemical brainstem studies have shown a reduction in the synaptic inputs to the lower auditory brainstem nuclei, which receive inputs from the spiral ganglion cells. Preliminary results involving the auditory nerve of these hyperbilirubinemic animals demonstrate a selective loss of the large-caliber axons in the auditory nerve with complete preservation of the outer hair cells.

The low threshold of activation and high spontaneous discharge rate of large-diameter axons that innervate inner hair cells in the cochlea are the electrophysiologic properties ideally suited for the temporal coding of auditory information, particularly as it relates to neural synchrony and temporally dependent auditory events, such as speech comprehension. Because hyperbilirubinemia has a direct association with AN/AD, this animal model, if proven, will have significant potential in helping investigators pinpoint the pathophysiology of AN/AD.

 

Frequency

United States

The exact frequency of auditory neuropathy/auditory dyssynchrony (AN/AD) has varied among different publications. Although the prevalence among all children is extremely low, when children with known hearing loss are examined, the rate increases dramatically. Some authors have suggested that the prevalence is 2-15% of children with known hearing loss. In a 2002 review of the prevalence, Sininger suggested that approximately 1 in 10 children with hearing loss and severely affected ABR test results have AN/AD. Overall, AN/AD is rare and can be found in an estimated 1-3 children per 10,000 births. Most patients with AN/AD have other significant perinatal risk factors. However, one third of the patients have no definable etiologic cause.

Race

Auditory neuropathy/auditory dyssynchrony (AN/AD) has no racial bias.

Sex

Auditory neuropathy/auditory dyssynchrony (AN/AD) occurs with near-equal frequency in males (55%) and females (45%).

Age

Although the insults that cause auditory neuropathy/auditory dyssynchrony (AN/AD) are thought to arise in the perinatal period, this disorder can also be diagnosed in adults. Because AN/AD is a relatively newly described condition, many adults may have not obtained the proper audiologic testing to reach a diagnosis of AN/AD. With the advent of newborn hearing screening tests, the delay in diagnosis of AN/AD should be minimized, which will expedite intervention.

Two thirds of the children with auditory neuropathy/auditory dyssynchrony (AN/AD) demonstrate risk factors associated with perinatal hearing loss (see Pathophysiology). AN/AD should be suspected in any child with slightly to severely abnormal hearing thresholds and severe speech and language delay out of proportion with the presumed hearing loss. In addition, adults with mildly to moderately abnormal pure tone thresholds and speech discrimination scores out of proportion with suspected hearing loss should undergo additional evaluation by an otologist or neurootologist. This evaluation should include a further audiologic workup with auditory brainstem response (ABR) and otoacoustic emission (OAE) testing to rule out the presence of AN/AD or other retrocochlear processes.[8]

The natural history of AN/AD is varied. Reports have included no change, improvement, and deterioration in children's ability to hear. Patients with AN/AD and associated hyperbilirubinemia have a more profound initial hearing loss but also have a greater tendency for improvement. Children with fever-associated hearing loss consistent with AN have also shown some resilience in their hearing loss. Understand that, although some recovery in the auditory system has been reported, most children affected by AN/AD continue to display abnormal pure tone averages and ABR test results that requires a lifelong commitment by the child, family, speech pathologist, and audiologist.

No hematologic workup is necessary to diagnose auditory neuropathy/auditory dyssynchrony (AN/AD). History and audiologic testing establish the diagnosis (see History and Other Tests).

See the list below:

• Imaging studies are not necessary in the newborn period.

• Once the diagnosis is made correctly, conservative treatment can be initiated. If the parents choose surgical intervention, high-resolution computed tomography scanning of the temporal bones should be performed. This test helps the otologist or neurootologist determine the possibilities of inner ear malformations that might contribute to the disorder. In addition, the inner ear can be visualized and preparations for cochlear implantation can be made.[9]

• Typically, magnetic resonance imaging (MRI) has no role in AN/AD.

See the list below:

• The most pertinent audiologic tests for auditory neuropathy/auditory dyssynchrony (AN/AD) are briefly summarized, as follows[2, 3] :

  • Pure tone audiogram testing: This is a graphic plot of a patient's thresholds of auditory sensitivity for pure tone (sine wave) stimuli. It does not test a patient's ability to process sound. This test shows only the patient's ability to hear sounds or tones.

  • Speech audiometry: These tests use spoken words and sentences rather than pure tones. Tests are designed to assess sensitivity (threshold) or understanding (intelligibility) of speech.

  • Acoustic reflex (AR) measures: This measures the contraction of the stapedius muscle in the middle ear. Deviation from the normal threshold on AR testing indicates potential abnormalities of the hearing nerve and auditory system.

  • Otoacoustic emissions (OAEs): These are measured by the presentation of a series of clicks to the ear through a probe inserted in the ear canal. This test measures the integrity of the outer hair cells of the cochlea and cochlear function. Cochlear microphonics (CMs) tests the function of the cochlea similarly.

  • Auditory brainstem responses (ABRs): This test uses scalp electrodes to measure electrical activity in response to sound clicks. Abnormal results of ABR testing indicate that the hearing nerve, as well as the brainstem nuclei, may not correctly process the sounds.

• Criteria for the diagnosis of AN/AD are as follows:

  • With the advent of newborn hearing screens, children with auditory detriments are being identified and treated at increasingly earlier ages. All of the following must be present in newborns to diagnose AN/AD:

    • Absent or severely abnormal ABR test results at maximal stimulus (100 dBnHL)

    • Normal outer hair cell function as determined by OAEs or CMs

    • Absent or elevated stapedial reflex thresholds

  • Suspect AN/AD in older children or adults with the following audiologic findings:

    • Pure tone thresholds are abnormal. The entire range of abnormalities, from near-normal to profound, may be seen. A more severe loss is usually displayed in the lower frequency thresholds.

    • Poor speech discrimination scores are out of proportion with the level of loss suspected based on the pure tone average.

    • The audiogram findings may vary some, but the overall milieu usually remains unchanged.

The treatment of patients with auditory neuropathy/auditory dyssynchrony (AN/AD) starts with the parents. Information should be made available to all parents of children with hearing loss. Once this is done and the condition is thoroughly understood, the proper supportive adjuvant therapies can begin. These include speech pathology, hearing aid placement, and use of other hearing devices. The use of hearing aids can begin with children at around age 3 months.

Children with AN/AD were once thought not to benefit from hearing aid amplification; however, recent studies demonstrate that 50% of children can benefit from placement of an amplification device. When children with AN/AD were tested with hearing aids, their speech discrimination scores improved and were more consistent with the degree of hearing loss expected via their pure tone audiometry scores. The use of hearing aids prior to cochlear implantation is currently recommended.

Once the child is aged approximately 6 months, behavior audiometry thresholds should be obtained. Because the presentation and thresholds of AN/AD are so varied, the determination of more accurate levels of hearing loss helps to dictate the future intervention necessary for each child.

Communicative devices, which are options for any child with mild to severe hearing loss, also pertain to children with AN/AD. The use of conventional hearing aids and frequency modulation (FM) systems can help a child develop necessary speech and language skills. If a child does not progress with hearing aid devices and shows limited speech discrimination abilities, cochlear implantation is the next viable option.

Cochlear implants were approved in 1984 by the US Food and Drug Administration for use in adults. Six years later, the approval expanded to children, and inclusion criteria expanded to include larger groups of individuals with hearing impairment. Today, approximately 6000 cochlear implants are placed annually for various causes of hearing loss. In 2001, the use of cochlear implantation was expanded to include children with AN.

Long-term results of cochlear implants in patients with AN/AD have been promising, with demonstrations that children with AN/AD who received implants had equivalent hearing abilities to other children of similar age with implants.

A literature review by Fernandes et al indicated that in children with AN/AD spectrum disorder, cochlear implants lead to improvements in hearing skills similar to those associated with cochlear implants in children with sensorineural hearing loss.[10]

A study by Liu et al found that children with AN/AD spectrum disorder who received cochlear implants prior to age 24 months tended to show better development of auditory and speech skills than did children who received the implants at a later age.[11]

If cochlear implantation fails, another option may exist in AN/AD, with brainstem implantation having been reported. With the continued expansion of indications for cochlear implantation, demonstration of the pathophysiology of AN/AD has become more crucial in helping to determine which children are indeed good candidates for the increasingly popular surgical treatment of hearing loss.[12]

Children with hearing loss require special attention. A multidisciplinary approach had been adopted by most, which includes an otologist or neurootologist, speech pathologist, genetic counselor, audiologist, and, possibly, a pediatric neurologist and neonatologist.

For excellent patient education resources, visit eMedicineHealth's Ear, Nose, and Throat Center. Also, see eMedicineHealth's patient education article Hearing Loss.