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Page Ten

Auditory neuropathy/auditory dys-synchrony: New insights

Hood, Linda J.

Section Editor(s): Mueller, Gus Page Ten Editor

doi: 10.1097/01.HJ.0000292487.82469.36
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1 I noticed the term “auditory dys-synchrony” in the title. What does that mean?

The term auditory dys-synchrony may provide a more comprehensive view of auditory neuropathy. An article by Berlin, Hood, and Rose discusses this recommendation and focuses on two primary underlying reasons.1

First, the auditory nerve itself may not be affected. 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 cochlear implants have proven beneficial in auditory neuropathy patients. Zeng et al. showed that patients with auditory neuropathy demonstrate primarily a timing deficit that is consistent with a lack of neural synchrony2 and Kraus et al. present a case discussion of evidence for neural asynchrony.3 So, for the remainder of this article, “AN/AD” will connote auditory neuropathy/auditory dys-synchrony.

2 That makes sense to me—AN/AD it is! Can you refresh my memory about how AN/AD is defined and identified?

Certainly, but you also might want to check our earlier review article.4 The term AN/AD applies to patients who 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 physiologic measures. Otoacoustic emissions (OAEs) reflect outer hair cell function and cochlear microphonics (CM) are another measure generated at least in part in the outer hair cells. In AN/AD patients, we expect the results on these two tests to be normal (assuming that there is no middle ear pathology).

Abnormal results on middle ear muscle reflex (MEMR) and ABR testing are consistent with dys-synchrony of the VIIIth nerve. This functional dys-synchrony is distinguished from space-occupying lesions, such as VIIIth nerve tumors, or multiple sclerosis in that results of radiologic evaluation are normal in AN/AD patients. Furthermore, the compound action potential (CAP) is generally present in patients with space-occupying lesions or multiple sclerosis, but is not seen in AN/AD patients.

3 You mentioned middle ear problems and I know that they affect OAEs. Is it still possible to identify and monitor AN/AD in patients with middle ear problems?

You're correct in thinking that even minor middle ear problems may prevent OAEs from being observed, but there is less effect on the cochlear microphonic. The CM is one of the electrical responses from the cochlea (others are the endocochlear potential and summating potential). Both OAEs and CM are affected by stimulus attenuation resulting from a conductive hearing loss. However, middle ear problems also attenuate the emission returning from the cochlea outward through the middle ear.

Since the OAE is a low-amplitude acoustic signal, even a minor middle ear problem may reduce or block the OAE.

Since the CM is an electrical response, it is recorded by electrodes attached to the scalp, as with the ABR. In this case, the hair cell response is picked up by the electrodes and thus is not dependent on conduction back out through the middle ear system. So, in patients with middle ear problems where OAEs are absent, it is often still possible to record the CM and thus have some indication of outer hair cell function.

4 How do I measure the CM and distinguish it from the ABR?

The CM is a cochlear response while the ABR is a neural response. There are several distinct differences between cochlear and neural responses. Use of appropriate recording methods makes it possible to differentiate these responses.

The most direct method to separate these responses is to compare responses obtained with rarefaction polarity stimuli with those obtained with condensation stimuli. Because CMs follow the characteristics of the external stimulus, the direction of the cochlear microphonic peaks will reverse with changes in stimulus polarity. For higher-frequency stimuli and clicks, neural responses such as the ABR may show slight latency shifts with polarity changes, but they do not invert. Therefore, cochlear and neural components generally can be distinguished based on whether or not the peaks reverse with the stimulus. Use of alternating polarity stimuli is not recommended since the CM will cancel and not be visible in the averaged response.

If responses are obtained without reversing polarity but at several stimulus intensities, it may still be possible to distinguish cochlear from neural components. The CM decreases in amplitude but does not increase in latency as the stimulus intensity decreases. In contrast, ABR waves increase in latency and decrease in amplitude as the stimulus intensity decreases. Thus, comparison of response latency at various intensities can help distinguish cochlear from neural responses. Further discussion of these issues can be found in an article by Berlin et al.5

5 I work in the schools and don't have ABR available. Is there anything I can do?

Yes, there is. While ABR testing provides part of the definitive diagnostic information, AN/AD patients characteristically show absent middle ear muscle reflexes. Many school systems routinely evaluate middle ear function using tympanometry and MEMRs. If a child has normal middle ear function and absent MEMRs that cannot be explained by peripheral hearing loss, then this information can provide a good first indication of a possible neural dys-synchrony disorder. If OAE testing is also available, then present OAEs, normal tympanometry, and absent MEMRs are a powerful set of diagnostic measures. Thus, absence of MEMRs in combination with normal OAEs can be very useful in screening children suspected of having AN/AD and these children would be candidates for further evaluation.

6 Is AN/AD the same thing as a “central” auditory processing disorder?

No, they are different for a number of reasons and we believe it is more useful, particularly from a management perspective, to clearly distinguish AN/AD from a central auditory processing disorder (“CAPD” or APD). Each has several distinguishing characteristics.

AN/AD is a peripheral neural synchrony disorder, with possibly a pre-neural site, while a central APD is generally more diffuse in nature with peripheral synchrony usually within normal limits. In AN/AD, the ABR and MEMRs are characteristically absent, while results on these tests are usually normal in central APD. Most importantly, cochlear implants are a management option in AN/AD, but are not useful in patients with central APD.

7 Children with severe-to-profound hearing loss characteristically have no ABR or MEMRs. Have any of these children been found to have OAEs?

Yes. To address this question, two groups of researchers have tested students at schools for the Deaf. The group from Kresge Hearing Research Laboratory has tested over 1000 children in schools for the Deaf in the United States. Approximately 1% of the students showed clear OAEs and 10% to 12% had OAEs suggestive of residual outer hair cell function.6 In a study carried out by researchers at the University of Hong Kong, 81 students, mostly of primary age, were screened with OAEs and two students had robust OAEs and were subsequently confirmed as having AN/AD.7

8 Regarding identification of AN/AD in infants, are there certain risk factors or case history information that I should look for?

Yes, there are. First, it is important to note that, while some patients have risk factors related to hearing loss in their history, there are also are a significant number of patients with no risk factors in their history.

There are several factors observed in a number of patients with AN/AD. These include hyperbilirubinemia ranging from just above normal to quite high, premature birth (25 to 36 weeks gestational age), and perinatal asphyxia.5,8–11 It should be noted that elevated bilirubin levels are seen in many newborns, so whether or not the actual occurrence exceeds the normal incidence is unclear. There does seem to be a high incidence of AN/AD in infants who have undergone exchange transfusions, so this is another possible risk factor. While the above factors have been observed and information about their occurrence obtained, it is important to remember that AN/AD in children without any risk factor is also a possibility.

9 Do we know the underlying reasons for AN/AD?

The variability observed in patients continues to suggest several possible mechanisms underlying AN/AD. Most writers agree with Starr et al. that the timing problems associated with AN/AD could be sensory, axonic, or dendritic in nature.12 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. Absence of inner hair cells with present outer hair cells demonstrated in animal models such as the Bronx waltzer mouse13 and the Beethoven mouse14 provides a biological precedence. Recently, this was shown in human infants as well through temporal bone histological studies,15 providing an important connection to its possible occurrence in humans. In contrast, some patients with AN/AD have demyelinating conditions such as hereditary motor sensory neuropathy, Charcot-Marie-Tooth, or other neural conditions.

Unfortunately, we do not yet have non-invasive clinical audiologic methods for differentiating among these sites, so case history, medical laboratory studies, and collaboration with neurologists are very important in evaluating patients with AN/AD. All of the possible sites result in auditory dys-synchrony and suggest similar management needs related to methods of communication.

10 So, if there are several possible underlying reasons for AN/AD, is there also variation among patients?

Definitely. As mentioned earlier, patients vary in demonstration of other peripheral neuropathies. Some patients have clear hereditary sensory-motor neuropathy. Others have less apparent neuropathy, which is only evident on clinical examination, and still other patients demonstrate no signs of neuropathy. Often the only complaint of patients in these latter two groups is difficulty hearing or understanding speech, particularly in noise. AN/AD is generally bilateral, although some patients have been identified with unilateral AN/AD. In an interesting study, Starr et al. describe three children with a temperature-sensitive AN/AD whose symptoms only become apparent with elevation of body temperature.16

As for clinical audiologic test results, pure-tone thresholds vary widely and, while most patients perform very poorly on word- and sentence-recognition tests, a few patients have some residual speech-recognition ability in quiet. However, in our experience, even those with some speech-recognition ability in quiet are unable to understand words or sentences in competing noise situations. What patients have in common are findings on physiologic auditory measures consistent with normal outer hair cell function and neural dys-synchrony. Starr et al. provide further discussion of variation in AN/AD.10

11 Does AN/AD run in families?

It can. A number of families have been identified with siblings with AN/AD. There are also parents with AN/AD who have children with this disorder. AN/AD appears to follow both recessive and dominant inheritance patterns. Identification of genes underlying AN/AD is being pursued by geneticists at several centers, including Louisiana State University Health Sciences Center in New Orleans and Boys Town Medical Center in Omaha. Since AN/AD does occur in families, it is important to consider it as a risk factor for subsequent siblings in families that have one member with AN/AD.

12 Are there any particular patient groups in which I should look for AN/AD?

There are several groups of individuals who may have AN/AD. These include children who fail to develop speech and language and patients who are thought to have a “central” auditory processing disorder. Another group is patients who are well fitted with up-to-date hearing aids but, despite good audibility of signals, derive very minimal or no benefit. Also, as shown by the two studies discussed earlier, these patient groups would include those who have been diagnosed as “Deaf” but have OAEs.

13 Does AN/AD change over time?

There is considerable variability among patients related to changes over time. Berlin et al. identified several progressions.1,17 These include:

Progressive loss of peripheral auditory integrity: Some patients show a retrograde loss of cochlear microphonics and OAEs, and become audiologically almost indistinguishable from peripherally deaf children. Such children have been successfully implanted and perform well with a cochlear implant.

Maintain: Some patients maintain cochlear microphonics and OAEs, but do not learn speech and language by auditory means alone. Visual information (e.g., Cued Speech, American Sign Language, signed English) is necessary for language learning. A number of patients in this group are successful cochlear implant users and have moved away from visual cues post-implant.

Worsening with peripheral neuropathy: Some patients show a worsening of symptoms and develop other peripheral neuropathies, such as hereditary motor-sensory neuropathy (e.g., Charcot-Marie-Tooth disease).

Partial recovery: Some patients seem to recover pure-tone sensitivity and awareness of sound, but continue to show desynchronized ABRs, robust cochlear microphonics, and normal OAEs. Speech and language are delayed, but develop. Whether or not they will experience difficulty in noise or have “central” APD remains to be determined as they get older.

14 Can hearing aids help the AN/AD patient?

Our experience with patients with AN/AD is that even those who may be able to discriminate some words or sentences in quiet are unable to discriminate even simple sentences in competing noise (even at a +10 signal-to-noise ratio). It is important to distinguish detection of sound, which AN/AD patients may be able to do, from the ability to discriminate speech, which is critical for developing language and understanding speech signals.

Hearing aids can improve detection of sound through amplification but, in our experience, are of minimal benefit in improving discrimination. In the children (now approaching 100) whom we follow in our database, we have not seen facilitation of speech and language development with hearing aids alone.1

15 I've heard that patients with AN/AD are receiving cochlear implants. Do they really work with these patients?

Cochlear implantation, while counterintuitive if one thinks of AN/AD as a true neural disorder, is a viable option for patients with AN/AD. The underlying physiology in some patients may include absence or malfunction of inner hair cells. This has been documented in animal models, where the inner hair cells have been destroyed, and in human infant temporal bones.13–15,18 It is also possible that electrical stimulation, as through a cochlear implant, can sufficiently synchronize activity of impaired neural elements to allow use of auditory information where acoustic stimulation does not.

Performance of AN/AD patients with cochlear implants supports the viability of this management option. The five children with cochlear implants reviewed by Shallop et al. demonstrated synchronous responses on physiologic tests and all showed significant improvement in sound detection, speech perception, and communication skills.19 These results are consistent with those reported by Trautwein et al. for a single child who demonstrated synchronous responses on neural response telemetry (NRT) and performance on behavioral tests comparable to non-AN/AD children with cochlear implants.20

16 How do you know that cochlear implants can “restore” synchrony?

The primary measure of dys-synchrony in AN/AD patients is the ABR. Shallop et al. demonstrated synchronous electrical auditory brainstem responses (EABR) in patients post-implant.19 They also obtained NRT that measures responses from the auditory nerve using the intracochlear electrodes as both stimulating and recording electrodes. They report that post-implant AN/AD patients show synchronous NRT responses similar to those observed in non-AN/AD cochlear implant patients.

MEMRs are also abnormal in AN/AD patients, and the absence of reflexes is generally ascribed to a problem in the afferent portion of the reflex arc (at least in patients whose middle ear system is normal). Using intraoperative video recording, Shallop and colleagues have observed contraction of the stapedius muscle in response to acoustic stimulation through the cochlear implant electrode array as another demonstration of synchronous response to auditory signals.

17 Are cochlear implants a treatment for adult AN/AR patients, too?

Most of the patients who have been implanted have been children and the published reports to date summarize results with children. A few adults have been implanted with generally positive results. While the reports from adults to date have been anecdotal, some report variable benefit when first tuned up, but improved ability to communicate within a short time. Also, like the usual cochlear implant patients, some are able to converse over the telephone.

18 Are there any communication methods that facilitate development of speech and language in children with AN/AD?

Our experience and that of others shows that learning speech and language through the auditory channel exclusively is very difficult in patients with AN/AD. We believe this is because it is difficult or impossible to achieve a clear and consistent auditory signal (unless the patient has a cochlear implant) in a dys-synchronous auditory system. We recommend use of visual communication methods (such as Cued Speech, sign language, or signed English) as a necessary component for language development. Auditory-Verbal (AV) therapy by itself, before cochlear implantation, has not worked in our practice as the sole method of teaching language to AN/AD children.

19 What about after cochlear implantation? Do management strategies change?

After cochlear implantation, many patients with non-AN/AD hearing loss rely more on auditory information and move away from visual cues. This seems to be the case as well with many of the AN/AD patients who have been implanted. While we don't recommend use of auditory information alone pre-implant, we do use an AV approach post-implant and have found this approach successful. We recommend slowly changing from auditory and visual cues to auditory cues alone post-implant. Abrupt removal of the communication system that a child has depended on prior to receiving a cochlear implant could interrupt smooth continuation of progress.

20 Where can I find more information? Is there anything available for parents or patients?

The professional literature related to AN/AD is rapidly increasing. Also, in 2001, a textbook titled Auditory Neuropathy: A New Perspective on Hearing Disorders, edited by Sininger and Starr, was published.21 This textbook summarizes contributions from scientists and clinicians to a conference, held in 1998, to gain insight into characteristics, evaluation, and management. The web site at Kresge Hearing Research Lab contains information that is updated periodically and links to other web sites; it can be accessed at www.kresgelab.org in the section titled “Information on Deafness.” One of the links is to a site managed by a parent of one of our first children found with AN/AD. It provides a forum for parents and patients to exchange information.

ACKNOWLEDGMENTS

Research at Kresge Hearing Research Laboratory is supported by NIH National Institute on Deafness and Other Communication Disorders, Kam's Fund for Hearing Research, American Hearing Research Foundation, National Organization for Hearing Research, Deafness Research Foundation, Marriott Foundation, Kleberg Foundation, Oberkotter Foundation, and Louisiana Lions Eye Foundation.

One of the primary objectives of audiologic testing is to identify auditory pathologies. Years back, armed only with the results of pure-tone air-conduction and bone-conduction thresholds, we usually were able to separate conductive from sensorineural disorders. In the early 1970s, immittance audiometry provided us the ability to further identify specific pathologies within these two general categories and, by the 1980s, the routine use of the ABR further enhanced our ability to identify more subtle pathologies of the cochlea and auditory neural pathways. Today, with the addition of OAEs to the audiologic test battery, we are able to identify unique pathologies that perhaps would have been misdiagnosed in years past.

One such disorder is auditory neuropathy or auditory dys-synchrony (AN/AD). This pathology, identified by means of physiologic measures, presents a distinctive pattern when the acoustic reflex, OAEs, ABR, and cochlear microphonic results are compared.

Only a handful of audio-logists have worked extensively with AN/AD patients. This month's Page Ten author, Linda Hood, PhD, is one of them. A few years ago, Dr. Hood visited these pages and provided us with the answers to some basic questions regarding AN/AD. Now, she's back to field queries on recent developments surrounding this unique dysfunction.

Dr. Hood is professor at the Kresge Hearing Research Laboratory of the Louisiana State University Health Sciences Center in New Orleans. She is a founder and past president of the American Academy of Audiology. You probably know her best from her book chapters, text books, and the many workshops on auditory physiologic testing that she has conducted in New Orleans (and the rest of the world as well). You've also seen her article reviews each year as a charter member of The Hearing Journal's “Journal Club.” Except for an occasional visit to Tipitina's, Linda spends her “spare time” teaching online courses for the Vanderbilt/CMU AuD distance-learning program.

As you read Dr. Hood's excellent article on AN/AD, you'll first realize that our skills for identification of auditory pathology have increased considerably since the days of simple air-conduction and bone-conduction threshold testing. More importantly, you'll see that our understanding of this interesting disorder continues to increase, and that promising treatment strategies for the AN/AD patient are emerging.

REFERENCES

1. Berlin C, Hood L, Rose K: On renaming auditory neuropathy as auditory dys-synchrony. Audiol Today 2001;13:15–17.
2. Zeng FG, Oba S, Garde S, et al.: Temporal and speech processing deficits in auditory neuropathy. Neuroreport 1999;10:3429–3435.
3. Kraus N, Bradlow AR, Cheatham MA, et al.: Consequences of neural asynchrony: A case of auditory neuropathy. J Assoc Res Otolaryngol 2000;1:33–45.
4. Hood, LJ: Auditory neuropathy: What is it and what can we do about it? Hear J 1998;51(8):10–18.
5. Berlin CI, Bordelon J, St. John P, et al.: Reversing click polarity may uncover auditory neuropathy in infants. Ear Hear 1998;19:37–47.
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12. Starr A, McPherson D, Patterson J, et al.: Absence of both auditory evoked potentials and auditory percepts depending on timing cues. Brain 1991;114:1157–1180.
13. Deol MS, Kocher W: A new gene for deafness in the mouse. Heredity 1958;12:463–466.
14. Bussoli TJ, Kelly A, Steel P: Localization of the bronx waltzer (bv) deafness gene to mouse chromosome 5. Mammalian Genome 1997;10:714–717.
15. Amatuzzi MG, Northrup C, Liberman MC, et al: Selective inner hair cell loss in premature infants and cochlea pathological patterns from neonatal intensive care unit autopsies. Arch Otolaryngol HNS 2001;127:629–636.
16. Starr A, Sininger Y, Winter M, et al.: Transient deafness due to temperature-sensitive auditory neuropathy. Ear Hear 1998;19:169–179.
17. Berlin CI, Goforth-Barter L, St. John P, Hood LJ: Auditory neuropathy: Three time courses after early intervention. Abstr Assoc Res Otolaryngol 1999;22:169.
18. Harrison RV: An animal model of auditory neuropathy. Ear Hear 1998;19:355–361.
19. Shallop JK, Peterson A, Facer GW, et al.: Cochlear implants in five cases of auditory neuropathy: Postoperative findings and progress. Laryngoscope 2001;111:555–562.
20. Trautwein P, Sininger Y, Nelson R: Cochlear implantation of auditory neuropathy. JAAA 2000;11:309–315.
21. Sininger YS, Starr A: Auditory Neuropathy: A New Perspective on a Hearing Disorder. San Diego: Singular Publishing Group, 2001.
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