Auditory Brainstem Implant Candidacy in the United States in Children 0-17 Years Old

Abstract

Introduction

Advances in neuroprosthetic technology have ushered in a new era for children with hearing loss. The auditory brainstem implant (ABI) is an option for hearing rehabilitation in profoundly deaf patients ineligible for cochlear implantation. No study has examined the potential population-level demand for ABIs in the United States (US). Herein, we aim to quantify the potential need for pediatric ABIs.

Methods

A systematic literature review was conducted to identify studies detailing the rates of congenital cochlear and/or cochlear nerve (CN) anomalies. Absolute indications for ABI include bilateral cochlea or CN aplasia (Group A), and relative indications for ABI include bilateral cochlea or CN hypoplasia (Group B). Data was subsequently correlated to the US Census Bureau, the National Health Interview Survey, and the Gallaudet Research Institute to provide an estimation of pediatric ABI candidates.

Results

Eleven studies documented rates of bilateral findings. Bilateral cochlea aplasia was identified in 0-8.7% of patients and bilateral CN aplasia in 0-4.8% of patients (Group A). Bilateral cochlea hypoplasia was identified in 0-8.7% of patients and bilateral CN hypoplasia in 0-5.4% of patients (Group B). Using population-level sensorineural hearing loss data, we roughly estimate 2.1% of children with severe to profound sensorineural hearing loss meet absolute indications for an ABI in the United States.

Conclusion

Congenital cochlear and cochlear nerve anomalies are exceedingly rare. This study provides the first preliminary estimate of cochlea and CN aplasia/hypoplasia at the population level albeit with limitations based on available data. These data suggest the need for dedicated ABI centers to focus expertise and management.

1. Introduction

Advances in neuroprosthetic devices and surgical techniques over the last 40 years have revolutionized treatment options for children born with severe to profound hearing loss. Cochlear implants (CI) have been at the forefront of this revolution, offering both sound and speech perception to pediatric patients worldwide.¹ The CI bypasses the non-functional hair cells of the inner ear to directly stimulate spiral ganglion neurons, the first order neurons of the auditory pathway. Over the past 50 years, over 300,000 individuals worldwide have received a CI.² Technology has evolving during this period from a single channel implant to a multichannel auditory neurostimulator providing sound and speech perception to the majority of deaf users. The recent Lasker Award, given to developers of the CI, highlights the overwhelming success of this device and its positive impact on society.³

There exist a small subset of deaf individuals, however, who will not benefit from the CI due to 1) a small or absent cochlea, 2) a small or absent auditory nerve, or 3) injury or scarring of the inner ear or auditory nerve secondary to meningitis, trauma, or tumor. The auditory brainstem implant (ABI) is the only option to provide hearing sensations in these patients who are not candidates for CI due to anatomic restrictions. The ABI bypasses the damaged or absent cochlea and auditory nerve to directly stimulate the cochlear nucleus (CN) in the brainstem.^4-9 More than 1,000 adult and pediatric patients worldwide have been successfully implanted with an ABI over the past four decades.¹⁰

Over the past decade, surgeons have begun implanting ABIs in pediatric patients who are unable to receive cochlear implants due to congenital or acquired malformations of the inner ear.¹¹ Outcomes have shown that sound and speech perception may actually result in auditory sound awareness or, in some cases, performance comparable to that of the CI.¹² This relatively new indication for the ABI has increased the number of operations throughout Europe in patients with congenital anomalies who previously had no chance of achieving auditory sensation.¹³ In the United States, ABIs are currently approved only for neurofibromatosis (NF2) patients ages 12 and above; however, FDA trials are now underway at four major care centers across the United States (Massachusetts Eye and Ear Infirmary, University of North Carolina-Chapel Hill, House Ear Institute, and New York University) to conduct ABI surgeries in non-NF2 children with congenital and acquired malformations of the cochlea and auditory nerve, as outlined in the 2008 Consensus report. ^14,15

Given that pediatric ABI implantation is still in its nascency and the patient population with bilateral congenital abnormalities is small, an accurate estimation of potential ABI patients is challenging. With new indications and patient populations for the pediatric ABI on the horizon, an important question is, “How many children are there that stand to benefit from this device?” This basic question has implications for device development, resource allocation, and surgical education. Previous studies have addressed the potential population-level needs for cochlear implants in the United States and Europe^16,17. Using a similar methodology, we aim to quantify the overall number of potential pediatric candidates for ABIs in the United States, as well as provide commentary about the number of necessary US “ABI Centers.”

2. Material and Methods

Previous studies, such as Bradham et al. and Davis et al., estimated the potential population need for cochlear implants in Europe and the United States.^16,17 Both studies employed similar population-based analyses to formulate rough estimates. Their methods included: 1) utilization of census-level data to estimate the number of deaf children in the population; 2) employment of ratios obtained from the literature to determine estimates for various exclusion criteria for cochlear implantation, e.g. neurological devastation, absence of the cochlear nerve, and presence of cognitive disorders. We employ an analogous methodology. The Massachusetts Eye and Ear Infirmary Institutional Review Board approved this study.

2.1 Indications for Pediatric Auditory Brainstem Implants

Using the 2011 consensus statement¹⁴ as a guide (see Table 1), potential ABI candidates were divided into two groups based on radiological classifications: absolute indications for the ABI (Group A) and relative indications for the ABI (Group B). Absolute indications included 1) bilateral cochlear aplasia, which included complete labyrinthine aplasia, and 2) bilateral cochlear nerve (CN) aplasia. Relative indications included 1) bilateral cochlear hypoplasia, 2) bilateral CN hypoplasia, 3) bilateral complete cochlear otosclerosis/ossification, and 4) bilateral trauma of the temporal bone. A flowchart showing an overview of this methodology is illustrated in Figure 1.

Table 1.

Radiologic Indications for Auditory Brainstem Implants in Pediatric Population based on Sennaroglu et. al. Consensus Statement, 2011.¹⁴

Well-Defined Congenital Indications	Possible Congenital Indications
1)Complete labyrinthine aplasia (Michel aplasia) 2)Cochlear aplasia 3)Cochlear nerve aplasia 4)Cochlear aperture aplasia	1)Hypoplastic cochlea with cochlear aperture hypoplasia 2)Common cavity and incomplete partition type I cases if the cochlear nerve is not present 3)Common cavity and incomplete partition type I cases if the cochlear nerve is present 4)The presence of an unbranched CVN, after insufficient response to CI 5)Hypoplastic cochlear nerve, if a sufficient amount of neural tissue cannot be followed into the cochlear space
Acquired Indications
1)Postlingually deafened children due to meningitis with severe ossification of the cochlea 2)Bilateral temporal bone transverse fractures with cochlear nerve avulsion 3)Cochlear otosclerosis with gross destruction of the cochlea, which is readily diagnosed on, computed tomography and MRI. 29

Figure 1.

Flowchart of methodology used to determine absolute and relative indications for ABI.

2.2 Literature Review of Cochlea and Cochlear Nerve Malformations

A literature review was conducted to comprehensively identify articles related to anomalies of the cochlea and/or cochlear nerve. We utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analysis checklist and statement recommendations to guide this qualitative systematic review.¹⁸ The initial search consisted of the following Medical Subject Headings (MeSH) terms: “Auditory Brainstem Implant”, “ABI”, “Cochlea/abnormalities”, “Cochlea/radiography”, and “Vestibulocochlear Nerve/abnormalities.” Inclusion criteria were studies that provided number of patients with cochlear aplasia, cochlear hypoplasia, CN aplasia, or CN hypoplasia. The studies were limited to human subjects under 18 years of age who were being evaluated for hearing loss or as a CI candidate. Exclusion criteria included non-English studies, case reports, and cohort size less than 20 without demonstration of the number of total charts reviewed. Data recorded from each of the included studies provided type of population studied, total population size, number with given anomaly, and methodology of determining anomaly.

2.3 Population Data of Severe to Profound Hearing Loss

The population-based data for children under 18 years of age was obtained from 2013 US Census Bureau population estimates.¹⁹ The Gallaudet Research Institute provides data on severe to profound hearing loss that is based on an independent analysis of the National Health Interview Survey (NHIS).²⁰ This estimate differentiates the prevalence of children with hearing loss based on self-reported or informant-reported functional status, categorizing individuals as having a “little trouble”, a “lot of trouble”, or “deaf”. The estimate therefore provides a rough estimate of the population of candidates for an auditory prosthetic device. These data, taken in conjunction with the U.S. Census population estimates, provide an estimate of the number of children currently living in the United States with severe to profound hearing loss.

2.4 Quantifying Potential ABI Candidates

Data from radiographic literature review described above were aggregated to determine the proportion of radiographic abnormalities of the study population. Based on previous published methodologies^16,17, this ratio was extrapolated using census-level population data of the number of deaf children in the United States to estimate the number of potential ABI candidates.

3. Results

3.1 Literature Review

The primary search identified a total of 706 articles. A total of 23 studies were found to have relevant patient data, using the inclusion and exclusion criteria as outlined above spanning from 1987 to 2013. Of these, 15 articles outlined cochlear abnormalities and 11 outlined CN abnormalities. No studies were found with prevalence data regarding complete cochlear ossification or sclerosis or bilateral temporal bone fractures. All patients had known SNHL and were being evaluated either for etiology of hearing loss (60%) or for possible cochlear implantation (40%). Five studies looked at unilateral hearing loss only, while the remaining looked either at bilateral only or a combination of the two. Data from each of these studies are outlined in Tables 2 and 3.

Table 2.

Unilateral and Bilateral Cochlea Abnormalities in Pediatric Populations Identified in Radiologic Studies

Study	Population	No. of Subjects	No. of Cochlear Aplasia (%)	No. of Cochlear Hypoplasia (%)
Jackler et. al.30	SNHL	63	3 (4.76%) 0 B, 3 U	7 (11.11%) 4 B, 3 U
Buchman et. al. 31	CI recipients	315	0 (0.00%)	4 (1.27%) unk.
Papsin et. al.32	CI candidates	298	0 (0.00%)	13 (4.36%) 12 B, 1 U
Sennarolgu et. al. 33	SNHL	23	3 (13.00%) 2 B, 1 U	2 (8.70%) 1 B, 1 U
Wu et. al. 34	SNHL	160	2 (1.25%) unk.	4 (2.5%) unk.
Purcell et. al. 35	SNHL	46	0 (0.00%)	4 (8.70%) 4 B, 0 U
Russo et. al. 36	“Profound” SNHL	24	0 (0.00%)	1 (4.16%) 1 B, 0 U
Song et. al. 37	Unilateral SNHL	322	3 (0.93%) 0 B, 3 U	2 (0.62%) 0 B, 2 U
Miyasaka et. al. 38	SNHL	21	2 (9.52%) 1 B, 1 U	0 (0.00%)
Mocan et. al. 39	Congenital SNHL	676*	5* (0.74%) n/a	24* (3.55%) n/a
Jeong et. al 40	CI recipients	454	2 (0.44%) unk.	10 (2.20%) unk.
Pakdaman et. al. 41	CI recipients	36	0 (0.00%)	3 (8.33%) unk.
Young et. al. 42	CI recipients	478	1 (0.21%) 0 B, 1 U	1 (0.21%) 1 B, 0 U
Friedman et. al. 43	Unilateral SNHL	49	0 (0.00%)	4 (8.16%) 1 B, 3 U
Masuda et. al. 44	Unilateral SNHL	69	0 (0.00%)	1 (1.45%) 0 B, 1 U
	Aggregate	3034	21 (0.69%)	80 (2.64%)

SNHL = Sensorineural Hearing Loss, B = Bilateral, U = Unilateral, unk = unknown laterality

^*data reported as number of ears only

Table 3.

Unilateral and Bilateral Cochlear Nerve Abnormalities in Pediatric Populations Identified in Radiologic Studies

Study	Population	No. of Subjects	No. of CN Aplasia (%)	No. of CN Hypoplasia (%)
Bamiou et. al. 45	CI referrals	237	6 (2.53%) 5 B, 1 U	1 (0.42%) 0 B, 1 U
Parry et. al. 46	CI candidates	56	2 (3.57%) 1 B, 1 U	7 (12.5%) 3 B, 4 U
Russo et. al. 36	“Profound” SNHL	24	1 (4.17%) 1 B, 0 U	2 (8.33%) 0 B, 2 U
Simons et. al. 29	SNHL	131	0 (0.00%)	3 (2.29%) 1 B, 2 U
Zanetti et. al. 47	CI recipients	52	1 (1.92%) 1 B, 0 U	1 (1.92%) 1 B, 0 U
McClay et. al. 48	SNHL	170	21 (12.35%) 5 B, 16 U	23 (13.53%) unk.
Laury et. al. 49	Unilateral SNHL	148	8 (5.41%) 0 B, 8 U	0 (0.00%)
Miyasaka et. al. 38	SNHL	21	4 (19.05%) 1 B, 3 U	3 (14.29%) 0 B, 3 U
Valero et. al. 50	CI recipients	807	0 (0.00%)	19 (2.35%) unk.
Young et. al. 42	CI recipients	478	7 (1.46%) 7 B, 0 U	3 (0.63%) 3 B, 0 U
Clemmens et. al.51	Unilateral SNHL	128	19 (14.84%) 0 B, 19 U	14 (10.94%) 0 B, 14 U
	Aggregate	2252	69 (3.06%)	76 (3.37%)

SNHL = Sensorineural Hearing Loss, B = Bilateral, U = Unilateral, unk = unknown laterality

The range of cochlear and/or CN anomalies varied widely throughout the studies, ranging from 0% to 19% of patients with Group A indications and from 0% to 15% of patients with Group B indications. Out of a total study population of 3034 patients, 21 (0.69%) had cochlear aplasia and 80 (2.64%) had cochlear hypoplasia; out of a total study population of 2252, 69 (3.06%) had CN aplasia and 76 (3.37%) had CN hypoplasia. Eleven of these studies gave information on the number of bilateral congenital anomalies. These data are outlined in Table 4. Out of a total population of 1002, 3 (0.30%) patients had bilateral cochlear aplasia, and 24 (2.40%) had bilateral cochlear hypoplasia; out of a total population of 868, 16 (1.8%) had bilateral CN aplasia and 7 (0.80%) had bilateral CN hypoplasia.

Table 4.

Bilateral Cochlea and Cochlear Nerve Abnormalities in Pediatric Population Identified in Radiologic Studies

Study	No. of Subjects	Bilateral Cochlear Aplasia	Bilateral Cochlear Hyoplasia	No. of Subjects	Bilateral CN Aplasia	Bilateral CN Hypoplasia
Bamiou et. al.45				237	5	0
Parry et. al.46				56	1	3
Zanetti et. al.47				52	1	1
Miyaska et. al.38	21	1	0	21	1	0
Russo et. al.36	24	0	1	24	1	0
Young et. al.42	478	0	1	478	7	3
Friedman et. al.43	49	0	1
Purcell et. al.35	46	0	4
Papsin et. al.32	298	0	12
Jackler et. al.30	63	0	4
Sennaroglu et. al.33	23	2	1
Aggregate	1002	3 (0.30%)	24 (2.4%)	868	16 (1.8%)	7 (0.80%)

3.2 Population Data and Number of Profoundly Deaf Children

In 2013, the US Census Bureau documented a total of 73,585,872 children in the age range of 0 to 17.¹⁹ According to predictions made by the Galludet Research Institute, 0.06% of children ages of 0 to 4 and 0.09% of children ages of 5 to 17 are likely to be deaf.²⁰ Based on these rates, we estimate that there are currently 60,267 deaf children in the United States.

3.3 Estimation of Pediatric Auditory Brainstem Implant Candidates

Using aggregated rates calculated from radiographic studies, we roughly estimate 21 out of 1,000 pediatric patients (2.1%) with severe to profound hearing loss meet criteria for absolute indications for ABI surgery (0.30% with bilateral cochlea aplasia and 1.8% with bilateral CN aplasia). Similarly, 32 out of 1,000 pediatric patients (3.2%) with severe to profound hearing loss meet criteria for relative indications for ABI surgery (2.4% with bilateral cochlea hypoplasia and 0.80% with bilateral CN hypoplasia) (Table 5). Extrapolating to the entire US population under the age of 18, this corresponds to roughly 181 children with bilateral cochlea aplasia and 1085 children with bilateral CN aplasia (~1.7 per 100,000 children). Using the same census-level data, we estimate roughly 1446 children with bilateral cochlea hypoplasia and 482 with bilateral CN hypoplasia in the US (~2.6 per 100,000 children).

Table 5.

Estimate of total pediatric population with absolute and relative indications for ABI

	Population		Absolute Indications		Relative Indications
Age Group	Totala	SPHLb	Bilateral Cochlear Aplasiae	Bilateral CN Aplasiaf	Bilateral Cochlear Hypoplasiag	Bilateral CN Hypoplasiah
0-4 years old	19,868,088	11,921c	36	215	286	95
5-13 years old	37,073,596	33,366d	100	601	801	267
14-17 years old	16,644,188	14,980d	45	270	360	120
Total	73,585,872	60,267	181	1085	1446	482
Estimated Number out of all patients <18 years old			0.25 /100,000	1.47/100,000	1.97/100,000	0.66/100,000

^aUnited States Census Bureau (2013)

^bSevere to profound hearing loss

^c0.06% of total population, based on Mitchell

^d0.09% of total population, based on Mitchell

^e0.30% of SPHL, based on aggregate data

^f1.8% of SPHL, based on aggregate data

^g2.4% of SPHL, based on aggregate data

^h0.80% of SPHL, based on aggregate data.

4. Discussion

Our study provides the first systematic review of radiographic studies on CN hypoplasia and aplasia, as well as cochlear hypoplasia and aplasia. We also provide a rough estimate of the number of patients at the population level in the United States with absolute and relative indications for auditory brainstem implants, albeit with significant methodological limitations. Without dedicated nation-wide survey, an accurate estimation of the prevalence and incidence number of these patients is challenging. We provide a first attempt to quantify potential candidates for ABIs based on previous methodology.^16,17

The indications for ABI surgery are continually evolving. We designed this study to provide an examination of the maximum number of potential ABI candidates based on previously published guidelines. We established two straightforward study groups: absolute indication for ABI (Group A: bilateral cochlea and CN aplasia) and relative indication for ABI (Group B: bilateral cochlea and CN hypoplasia). There are several factors, however, within this population of patients that may preclude them from undergoing an ABI surgery. Davis et al. estimated that 33% of the hearing impaired population would refuse CI implant surgery due to either severe cognitive disorders, brain damage, or family opposition.¹⁶ This estimate may be even higher in the ABI candidate population. Studies looking at patients with cochlear aplasia have found correlations with congenital syndromes, e.g. CHARGE, in 58-60% of cases ^21,22; these patients may not qualify for ABI surgery due to more serious medical comorbidities and/or lack of cognitive ability for meaningful improvement in communication. Moreover, there are several psychosocial factors that should be considered in this population including parents’ involvement, health insurance status, and geographic restraints. Taken together, these additional factors would likely further decrease the number of ABI procedures.

Estimates from this paper as well as historical data and trends indicate that there will likely be a small but continued need for ABI surgery. More specifically, it is estimated that 15 children have been implanted with ABIs in the United States and over 150 pediatric cases across the world since 2001. There are likely many more children who are being evaluated. Further, there are presently four sites with ongoing FDA-approved trials for pediatric ABI implantation, however, there is increased interested for new centers that may fill need based on geographic constraints. Consequently, it seems reasonable that given the limited population of patients and the high-complexity of the surgical case, the expertise of neurotologists, neurosurgeons, audiologists and anesthesiologists should be centered to provide familiarity with the pre-operative evaluation, procedure, post-operative care and audiologic therapy required for successful ABI use. Because outcomes improve with increasing experience, it stands to reason that dedicated centers should provide this care.^23,24

We acknowledge that our investigation has several limitations. Estimation of a rare condition is challenging, and use of radiographic data from the international community contains inherent bias when applied to the US population. In addition, the articles cited in this paper occurred over a roughly 20 year period, it is unclear if there were overlapping patients and if population growth would have influenced aforementioned results. In terms of other limitations, estimates of radiographic abnormalities showed significant heterogeneity. This may be due to differences in definitions of congenital cochlear and cochlear nerve abnormalities, sample size, target study population, and methods of data collection amongst the studies (e.g. MRI or CT). There may be large cohorts of children with negative radiology findings whose results are never included in published studies. Moreover, given the extreme rarity of these congenital findings, it is possible that patients with these anomalies were reported only as case studies. Several such studies exist documenting cases of bilateral cochlear aplasia and CN aplasia ^25-27, and including these patients in such case studies may actually increase our estimates. In addition, there may be studies beyond radiographic analyses that point to indications for auditory brainstem implantation, such as poor CI outcomes due to undisclosed anatomic abnormalities, trauma or bilateral cochlear ossification from meningitis. Taken together, it is unclear how these collective limitations may affect our estimate of ABI candidates.

Despite these limitations, we view our calculation of ABI candidacy in the United States as a reasonable upper limit and starting point for further investigation and discussion. While we acknowledge that not all of our estimated candidates will result in an ABI surgery, such as developmental delay precluding surgery, our data also is useful both for estimation of resource allocation and need for further device development. Furthermore, our paper highlights the critical need for standardized reporting of cochlear and cochlear nerve malformations. Future studies should seek to highlight which patients would benefit from a cochlear implant versus an ABI based on radiographic findings.

5. Conclusion

Our study provides the first systematic review of cochlear and CN aplasia and hypoplasia. We find that these anatomical abnormalities are exceedingly rare. Further, we estimate the number of potential ABI cases per year in the United States. Our study has implications for management of pediatric patients who are ABI candidates, including perioperative and postoperative audiology care, as well as future population-level research relevant to children with severe to profound hearing loss.