Jeffrey L. Simmons, MA, CCC-A
In 2008, a group composed of audiologists, hearing scientists, medical geneticists, neonatologists, and neurologists met in Como, Italy, for the Guidelines and Development Conference on the Identification and Management of Children With Auditory Neuropathy. The goal of the conference was to discuss a myriad of issues related to this auditory disorder, which is characterized by apparently normal outer hair cell function in combination with impaired or absent conduction of synchronous signals by the auditory nerve. Among the many outcomes of the conference was a consensus to change the terminology used for referring to this particular type of hearing impairment to auditory neuropathy spectrum disorder (ANSD). Another outcome was the recommendation that cochlear implantation be considered as a treatment option in the event of poor progress in auditory language development and speech understanding, regardless of behavioral audiometric thresholds. This is a considerable departure from the first years after ANSD was identified and classified as a possible neural disorder (Sininger, Hood, Starr, Berlin, & Picton, 1995; Starr, Picton, Sininger, Hood, & Berlin, 1996). At that time, it was often supposed that cochlear implants would not be a viable option for remediation in this population. The recommendation echoes that made by the Joint Committee on Infant Hearing (2007), whose current position statement indicates that cochlear implantation should be given careful consideration for any child who experiences only limited benefit from appropriately fit amplification.
There were logical bases for assuming that a cochlear implant would not be an appropriate or especially successful intervention for what the early ANSD researchers thought was hearing loss due to a neural degenerative condition. In the case of a pathology that was demyelinating, the result could be desynchronous conduction of electrical stimulation across nerve fibers. Alternatively, if it were the axons that were the site of lesion, there would likely be at least a partial conduction block in the nerve that could reasonably be expected to worsen. If the pathology were localized to the spiral ganglion, there could be a problem with the entire auditory nerve not being excitable (Starr, Picton, & Kim, 2001).
Even assuming that the site of lesion was in fact in the auditory nerve, however, there were still reasons to at least consider the idea that cochlear implantation might be an effective intervention. For example, Zhou, Abbas, and Assouline (1995) demonstrated that electrical stimulation of demyelinated nerves in mice resulted in a measurable auditory brainstem response (ABR) waveform. It has also been shown that if a nerve fiber is stimulated electrically, both the growth of discharge rate and the maximum rate achievable are greater than when stimulating the nerve acoustically. In addition the timing of the nerve response to electrical stimulation seems to be more precise and repeatable than it is for acoustic stimulation. Period histograms of neural responses show that spikes in the action potential occur more often around the phase peak when using electrical stimulation than when using acoustic stimulation, for which the spikes are more spread out along the entire phase curve (Abbas, 1993). The suggestion has also been offered that the discrete biphasic pulses used in most cochlear implant stimulation strategies may assist in increased synchrony of the firing pattern of the auditory nerve (Rance, 2005). Finally, the fact should not be overlooked that there can also be deterioration of the auditory neurons in patients with deafness due to sensorineural hearing loss, and these are the type of patients for whom cochlear implants were specifically developed and who typically benefit significantly from the device (Spoendlin & Schrott, 1989).
The earliest reports in the peer-reviewed literature involving cochlear implantation in individuals with ANSD were not particularly promising and supported the assumption that implants would not show much success in patients with this disorder (Miyamoto, Kirk, Renshaw, & Hussain, 1999; Rance, Beer, & Cone-Wesson, 1999). The 2 patients presented in these studies showed only marginal improvement or virtually no improvement at all compared with preimplant auditory performance. Shortly thereafter, however, two articles were published which suggested that perhaps some patients with ANSD could benefit from a cochlear implant. Both described single patients who exhibited synchronous activity in the auditory nerve following cochlear implantation (Fabry, 2000; Trautwein, Sininger, & Nelson, 2000). In 2001, a report from the Mayo Clinic described 5 children with ANSD who had received cochlear implants. Short-term outcomes for the 5 were reported to be similar to those of typical pediatric implant recipients with sensorineural hearing loss (Shallop, Peterson, Facer, Fabry, & Driscoll, 2001). The authors suggested that cochlear implantation could be an effective form of remediation in some cases with ANSD. This study was ultimately followed up with another that reported on the original 5 children with ANSD plus 5 additional children. They were compared with 10 matched controls. Programmed stimulation levels from the implant and sound-field detection thresholds did not differ between cochlear implant recipients with ANSD and the controls with sensorineural hearing loss. Statistical analyses were not performed on speech perception or education placement/communication mode, but the authors reported that both the ANSD group and the controls were performing about equally (Peterson et al., 2003). The emergence of studies such as these appeared to lead an increasing number of centers to consider and explore the use of cochlear implants as a remediation option in cases involving ANSD.
Multiple reports in the literature have claimed successful or positive outcomes for individuals with ANSD who have received cochlear implants. Although lacking some detail with respect to outcome test results, several studies describe performance of cochlear implant recipients with ANSD to be comparable to that of the general population with cochlear implants (Buss et al., 2002; Madden, Rutter, Hilbert, Greinwald, & Choo, 2002; Rodriguez Ballesteros et al., 2003). On the other hand, there have been reports in the literature that have detailed the scores of outcome measures that either show improvement over preimplant performance or appear to fall within the range of normal limits for implant recipients in general (Mason, De Michele, Stevens, Ruth, & Hashiaki, 2003; Zdanski, Buchman, Rousch, Teagle, & Brown, 2006). Other studies have gone beyond description reports of outcomes and conducted more comparative analyses. Gibson and Sanli (2007), in a study involving perhaps the largest cohort of ANSD patients with cochlear implants to date, reported that 75% of their 60 participants had speech perception scores equal to controls with sensorineural hearing loss. Jeong, Kim, Kim, Bae, and Kim (2007) compared cochlear implant performance outcomes for 6 children with ANSD to matched controls with sensorineural hearing loss. There were no statistically significant differences between the two groups on the measures of speech perception ability used in the study. Zeng and Liu (2006) reported on speech perception as function of signal-to-noise ratio in 5 cochlear implant recipients with ANSD and compared them to 8 implant recipients with sensorineural hearing loss. In general, the 5 individuals with ANSD performed worse than the best implant users from the group without ANSD but similarly to the average users from the group without ANSD. In a slight contrast to these various studies, however, it is interesting to note the findings reported by Rance and Barker (2007). Although the recipients with ANSD in their study derived definite benefit from the cochlear implant, their open-set speech perception scores showed an overall tendency to be poorer than those seen for the implant recipients with sensorineural hearing loss.
The majority of the published reports of individuals with ANSD who receive a cochlear implant have involved pediatric patients. This may be related to the fact that it seems a large proportion of adults with the diagnosis have a peripheral nerve disease (Starr, Sininger, & Pratt, 2000), and, as mentioned earlier, there may be some hesitancy in implanting due to assumptions about limited outcome. A recent report, however, describes cochlear implantation in 3 adults diagnosed with ANSD, at least 2 of whom had true peripheral neuropathies (De Leenheer, Dhooge, Veuillet, Lina-Granade, & Truy, 2008). The 2 individuals with diagnosed neuropathy experienced significant improvement in speech perception and auditory performance. The third adult did not benefit as much as the other 2, but there was still an improvement of 48% for open-set speech perception of disyllabic French words. Shallop (2002) presented 2 case studies of adults diagnosed with ANSD who received cochlear implants. Both reportedly had successful outcomes characterized by indicators such as ease of phone use and improved speech understanding in background noise. Mason et al. (2003) detailed 2 adult patients with the disorder in question who received cochlear implants. Speech perception score for Hearing in Noise Test sentences was 98% postimplant for 1 patient and increased from 4% preimplant to 42% postimplant for the second. It appears, therefore, that cochlear implants can have a positive outcome for adults with this disorder as well as for children, even when the site of lesion may have a greater tendency to involve the auditory nerve itself.
One might wonder why the implant has shown such success in many of the reported cases when it once appeared that a cochlear implant might be ineffective for patients with ANSD. Certainly one reason is related to site of lesion. It is now commonly held that for many individuals with this disorder, the pathophysiology involves either the inner hair cells or the synapse between the inner hair cells and the VIIIth nerve rather than the nerve itself, particularly among young children with ANSD. In those cases, the cochlear implant would be expected to bypass the site of lesion just as it would for a patient with typical sensorineural hearing loss. Even in instances in which the auditory nerve is the site of lesion, however, there is still an explanation regarding why the cochlear implant may yield positive outcomes. As mentioned earlier, electrical stimulation can be more effective at producing a synchronous neural response than acoustic stimulation. For a compromised auditory nerve not able to adequately transmit a signal delivered acoustically, the discrete electrical pulses from the cochlear implant may be less affected by the impaired function and increase or restore synchronous firing activity in the nerve.
Recently, some researchers have suggested that cochlear implants be recommended for all patients with ANSD who do not benefit from conventional amplification (Jeong et al., 2007; Postelmans & Stokroos, 2006). With numerous studies suggesting no significant difference in outcomes for cochlear implant users with ANSD compared to those without, how reasonable is it to expect similar benefit for all patients with the ANSD phenotype? Should cochlear implantation be the standard treatment for this disorder? In response to that question, it should first be reiterated that there are some reports of limited benefit from cochlear implants in this population (Miyamoto et al., 1999; Rance et al., 1999). Gibson and Sanli (2007) reported that 15 of the 60 participants in their cohort with ANSD had abnormal electrically evoked auditory brainstem responses (EABR) and speech perception skills poorer than a control group of cochlear implant recipients with sensorineural hearing loss. The authors attributed this outcome to the presence of true auditory neuropathy in these individuals.
The fact that "neuropathy" was retained in the new terminology agreed on for this disorder serves to remind us that the original supposition of a neural site of lesion still holds true for at least some patients diagnosed with ANSD. The neural degenerative condition of Friedreich ataxia was present in the patient reported by Miyamoto et al. (1999). There are other conditions involving neuropathy of peripheral nerves that have been associated with hearing loss and ANSD. These include Leber's optic neuropathy, Stevens-Johnson syndrome, Ehlers-Danlos syndrome, and Charcot-Marie-Tooth (CMT) disease, also known as hereditary motor sensory neuropathy. Depending on the severity of neural involvement, diseases such as these could logically be expected in some cases to affect transmission of signals from the cochlear implant to the auditory cortex. Postelmans and Stokroos (2006) presented a case of an adult with CMT who received a cochlear implant. Although the authors reported that the outcomes were comparable with other cases of implantation in individuals with ANSD, speech perception scores went from 50% before the implant to 59% after the implant. It might be argued that this performance does not meet the results seen in the typical cochlear implant recipient. Patients with deafness-dystonia-optic neuronopathy (DDON) syndrome (Mohr-Tranebjaerg syndrome) can display the ANSD phenotype due to loss of spiral ganglion cells in conjunction with preserved cochlear function. A recent report of cochlear implantation performed in a young patient with DDON noted only fair performance with the cochlear implant overall and speech-language skills markedly below age-appropriate norms (Brookes et al., 2008). Zdanski et al. (2006) reported results of cochlear implantation for a child who exhibited signs of an unspecified peripheral neuropathy beginning at age 2. By 18 months postimplant, although sound-field thresholds with the cochlear implant were within the typical range, open-set word recognition for monosyllables was not significantly changed from preimplant levels measured with the use of hearing aids. Further, the authors were not able to elicit measurable responses during electrically evoked compound action potential testing either intraoperatively or at follow-up sessions. This would tend to suggest that the implant was not as effective at restoring synchronous firing activity in the auditory nerve as is typically expected in cochlear implant recipients. Consequently, it is apparent that in some instances where an actual neural pathology is present, outcomes with the cochlear implant may be more limited than in recipients with nonneural site of lesion.
Buchman et al. (2006) described a condition labeled "cochlear nerve deficiency" in 9 individuals from a cohort of 51 patients diagnosed with ANSD. The researchers found either absent or abnormally small auditory nerves by examining magnetic resonance imaging (MRI) findings rather than relying only on computed tomography (CT) scans of the temporal bone, which in the majority of their cases would have missed the neural anomaly. Walton, Gibson, Sanli, and Prelog (2008) also used MRI in conjunction with CT scans and reported finding either small or absent cochlear nerves in 15 of the 54 ANSD patients in their study. While all of them received cochlear implants, only 2 of those 15 participants developed open-set speech perception abilities. The others had postimplant performance considered to be poorer than that typically expected in pediatric implant recipients. Bradley, Beale, Graham, and Bell (2008) published a report on 6 pediatric cochlear implant recipients with hypoplastic auditory nerves, 2 of whom had present otoacoustic emissions and cochlear microphonics and a resulting diagnosis of ANSD. None of the participants reached auditory performance levels typically expected of the general population of pediatric cochlear implant users.
This is not to suggest that these patients should be globally denied or should unequivocally not receive a cochlear implant. Rather, they should be comprehensively assessed for any auditory sensation, and there should be thorough counseling either for the parents or for the patient regarding the possibility of limitations in outcomes. It is interesting to note that in the Walton et al. (2008) study, 2 children whose MRI findings suggested bilaterally absent auditory nerves were ultimately implanted. Not unexpectedly, they had poor outcomes with respect to auditory/oral communication outcomes. However, both of the children exhibited some responses during EABR testing, suggesting that there were some auditory nerve fibers present beyond the resolution of the MRI. Other reports have noted similar cases in which some participants with apparently absent cochlear nerve tissue, per MRI results, have received cochlear implants and, although achieving lower speech perception outcomes, have nevertheless exhibited behavioral responses to auditory stimuli (Bradley et al., 2008; Govaerts et al., 2003). Arguably, any increased access to auditory information is of benefit, and research has suggested that this can sometimes be a reasonably expected outcome even in cases where the pathophysiology is linked to the auditory nerve. However, every effort should be exercised to make it clear that (a) individuals in this category may well not achieve the same results as implant recipients with nonneuropathic hearing loss and (b) alternative communication modalities may still be necessary.
Another reason to exercise caution in proceeding with cochlear implantation in infants and young children diagnosed with ANSD involves the chance that auditory function may improve. In one study on ANSD, 9 of 18 participants showed evidence of spontaneous improvement in hearing within the first 15 months after diagnosis. Four of the children recovered to essentially normal hearing levels (Madden et al., 2002). Psarommatis et al. (2006) reported that 13 children from a group of 20 study participants with ANSD exhibited ABR recovery with waveforms observable down to at least 40 dB nHL. Another report described improvement of auditory function in 5 children diagnosed with ANSD, 4 of whom ultimately had ABR thresholds within normal limits (Attias & Raveh, 2007). Factors that seemed most closely associated with potential recovery of auditory function included low birth weight with associated central nervous system immaturity and hyperbilirubinemia. Although there is a trend toward increasingly earlier age of implant, it would appear that a more cautious approach is warranted when ANSD is present, because the disorder can be transient and show improvement in some instances. It seems prudent to wait until the child is at least in the 12- to 16-month age range and repeated ABR and/or behavioral testing has indicated that the hearing impairment is stable and permanent. Finally, because ABR results do not correlate with the behavioral audiogram, it appears wise to obtain behavioral measures of auditory sensitivity. Certainly, this should be a minimum requirement before performing bilateral cochlear implantation, which is becoming more frequent in pediatric cochlear implant recipients.
A final question with regard to cochlear implants and ANSD involves the issue of providing the implant for patients whose auditory thresholds are in a range much better than that seen in the traditional or typical cochlear implant candidate. As mentioned in the introduction, the conference in Como, Italy, resulted in the recommendation that a cochlear implant be considered as a treatment option for patients with ANSD, regardless of behavioral audiometric threshold, if progress in auditory language development has been poor.
In the past, individuals with mild to moderate hearing loss have been considered to have hearing sensitivity that is "too good" for a cochlear implant. It is generally assumed that listeners with this degree of loss would perform quite well in terms of aided speech perception with acoustic amplification and that cochlear implantation would result in unnecessary loss of residual hearing. However, what about patients with ANSD who continue to show poor speech perception despite appropriately fit amplification and good audibility of the long-term average speech spectrum? Previous research in ANSD has established that a significant proportion of individuals with this disorder exhibit poorer than expected speech perception abilities and that the behavioral audiogram does not serve to predict speech perception scores. As has been indicated above, research regarding individuals with ANSD who received cochlear implants has suggested that the device can potentially restore synchronous function to the auditory nerve. It would seem reasonable to suggest, then, that a patient who is not showing progress in development of auditory/oral communication skills might do better with a cochlear implant, regardless of preimplant behavioral thresholds. If residual hearing, even of significant amount, is ultimately not useful in facilitating communication, perhaps there would be less concern in sacrificing it than there might be in a case of sensorineural hearing loss that could benefit from less invasive, conventional amplification. This would seem to be the reasoning behind the recent recommendations from the experts who met at the 2008 conference in Italy.
There is a scarcity of published data specifically regarding patients with milder hearing loss due to ANSD who have received a cochlear implant, although anecdotally this does seem to be occurring. Shallop (2002) briefly described a patient in her 20s with ANSD and mild to moderate hearing loss in both ears. She received a unilateral implant and reportedly was able to do better on word recognition tests in her implanted ear than in her unimplanted ear as well hear better in noise conditions than she had done preimplant. In the interest of promoting evidence-based practices, there is definitely a need for further published reports of this type to provide support for the rationale underlying the recommendation for extending cochlear implants to patients with milder degrees of hearing loss.
When considering implantation for children with ANSD and milder degrees of hearing loss, it appears that a cautious and methodical approach would once again be prudent. Although numerous articles published on this disorder echo the idea that speech perception in patients with this disorder is poorer than would be expected from the behavioral audiogram, there is evidence suggesting that this is not always true and may be an overgeneralization. For instance, in a study of 15 children with ANSD, approximately 50% showed open-set speech perception ability similar to matched controls with sensorineural hearing loss (Rance, Cone-Wesson, Wunderlich, & Dowell, 2002). Rance (2005) presented a meta-analysis of reported speech perception scores in patients with ANSD. Performance was compared with data from a study by Yellin, Jerger, and Fifer (1989) that established a range of speech perception ability expected for adults with varying degree of hearing loss. Of the 46 participants with ANSD for whom scores were available, 44% exhibited performance within the range expected according to the Yellin et al. article. Similarly, aided speech perception scores in some patients with ANSD are actually comparable to those seen in sensorineural hearing loss (Rance & Barker, 2007). Unfortunately, this cannot be predicted from the audiogram alone. Instead, each individual must be adequately assessed to determine whether he or she is in the category of patients who can derive significant benefit from hearing aids.
Consequently, before proceeding with cochlear implantation in a case of ANSD where hearing sensitivity is overall in the mild to moderate range, the responsible approach would seem to be a trial with amplification. If the patient is a young child, adequate assessment by a team of audiologists, speech-language pathologists, and early interventionists or educators of the deaf is needed to determine the efficacy of that amplification. If appropriately fit aids do not seem to be resulting in satisfactory speech perception or development of speech-language skills, the option of cochlear implantation could be considered. Naturally, for pediatrics, this might necessitate waiting until the child is slightly older than the 12- to 18-month range at which implantation is now commonly occurring for those with profound sensorineural hearing loss. Further published research with regard to this issue is needed, and implant teams will need to use their experience and expertise to carefully weigh the drawbacks of temporarily delaying amplification with the risk of possibly sacrificing residual hearing that may ultimately have responded to remediation with less invasive and irreversible means.
In summary, the evidence indicates that cochlear implants can often be an effective remediation for ANSD. Nevertheless, careful consideration should be given to the particulars in each case. Also, in cases where the diagnosis of ANSD has been made, a thorough, multidisciplinary evaluation by pediatric audiologists, speech-language pathologists, early interventionists, and physicians familiar with the unique characteristics of this disorder should be conducted before moving automatically toward implantation. Use of MRI is strongly encouraged for patients with ANSD who are being considered for cochlear implantation, especially when there is no behavioral evidence of auditory sensation. Clinicians must bear in mind the fact that ANSD encompasses a heterogeneous population with varying etiologies and sites of lesion despite the fact that patients present with a similar constellation of testing findings. This can obviously lead to variation in outcomes. There is no one single remediation that can be expected to be universally successful. A flowchart [PDF] illustrating a suggested protocol for management of patients with ANSD has been developed by the author for your consideration.
Jeffrey Simmons presently serves both adults and children with hearing impairment in his role as the clinical coordinator for the Cochlear Implant Clinic in the Lied Learning and Technology Center for Childhood Deafness and Vision Disorders at Boys Town National Research Hospital, in Omaha, Nebraska. In 1999, Simmons began working with his first patient diagnosed with the condition we now know as auditory neuropathy spectrum disorder (ANSD). Simmons has remained especially interested in this particular hearing disorder since that time, and he has been involved in a number of publications and presentations regarding various aspects of the diagnosis and remediation of ANSD. Contact him at firstname.lastname@example.org.
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