Cochlear Implantation in Children with Auditory ...

J Am Acad Audiol 23:5–17 (2012)

Cochlear Implantation in Children with Auditory Neuropathy Spectrum Disorder: Long-Term Outcomes DOI: 10.3766/jaaa.23.1.2 Alyce I. Breneman* Rene´ H. Gifford† Melissa D. DeJong*

Abstract Background: Best practices concerning the audiological management of the child diagnosed with auditory neuropathy spectrum disorder (ANSD) have not been definitively defined nor fully understood. One reason is that previous studies have demonstrated conflicting findings regarding the outcomes of cochlear implantation for children with ANSD. Thus, the question remains whether children with ANSD are able to achieve similar outcomes following cochlear implantation as those children with sensorineural hearing loss (SNHL). Purpose: To assess speech perception outcomes for children with cochlear implants who have a diagnosis of ANSD as well as their age-matched peers who have sensorineural hearing loss. Research Design: Retrospective study Study Sample: Thirty-five subject pairs (n 5 70) ranging in age at implant activation from to 10 to 121 mo (mean 39.2 mo) were included in this retrospective study. Subjects were matched on variables including age at initial implant activation and months of implant use at postoperative test point. Data Collection and Analysis: Speech recognition scores for monosyllabic and multisyllabic stimuli were compared across the subject groups. For those not developmentally and/or linguistically ready for completion of open-set speech recognition testing with recorded stimuli, GASP (Glendonald Auditory Screening Procedure) word recognition and/or questionnaire data using either the LittlEARS or Meaningful Auditory Integration Scale were compared across the groups. Statistical analysis using a repeated-measures analysis of variance (ANOVA) evaluated the effects of etiology (ANSD or SNHL) on postoperative outcomes. Results: The results of this study demonstrate that children with ANSD can clearly benefit from cochlear implantation and that their long-term outcomes are similar to matched peers with SNHL on measures of speech recognition. There were no significant differences across the ANSD and SNHL groups on any of the tested measures. Conclusion: Cochlear implantation is a viable treatment option for children with a diagnosis of ANSD who are not making auditory progress with hearing aids that have been fit using the Desired Sensation Level method (DSL v5.0). Expected outcomes of cochlear implantation for children with ANSD, excluding children with cochlear nerve deficiency, are no different than for children with non-ANSD SNHL. These results are important for counseling families on the expected outcomes and realistic expectations following cochlear implantation for children with ANSD who demonstrate no evidence of cochlear nerve deficiency. Key Words: Auditory neuropathy spectrum disorder, children, cochlear implants, outcomes, sensorineural hearing loss, speech perception tests

*Department of Otorhinolaryngology, Mayo Clinic, Rochester, MN; †Department of Hearing and Speech Science, Vanderbilt University, Nashville, TN Alyce I. Breneman, 200 First Street SW, Rochester, MN 55905; E-mail: [email protected]; Phone: 507-266-1965; Fax: 507-266-0663

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Journal of the American Academy of Audiology/Volume 23, Number 1, 2012

Abbreviations: ABR 5 auditory brainstem response; ANSD 5 auditory neuropathy spectrum disorder; CM 5 cochlear microphonic; CND 5 cochlear nerve deficiency; EABR 5 electrical auditory brainstem response; ECAP 5 electrically evoked compound action potential; GASP 5 Glendonald Auditory Screening Procedure; LNT 5 Lexical Neighborhood Tests; MLNT 5 Multisyllabic Lexical Neighborhood Test; OAE 5 otoacoustic emission; PBK 5 Phonetically Balanced Kindergarten word list; PECS 5 Picture Exchange Communication System; PTA 5 pure tone average; SNHL 5 sensorineural hearing loss

A

uditory neuropathy is an auditory disorder characterized by normal outer hair cell function in conjunction with absent or abnormal auditory nerve function. Because the auditory system is unable to produce a synchronous response to sound, it results in degraded processing of temporal speech cues (Zeng et al, 1999; Rance et al, 2004). Although individuals with this diagnosis may present with a wide range of hearing losses, they often complain of unusual difficulty understanding speech, especially in noise. With young children, auditory neuropathy can have a significant effect on language development. Since auditory neuropathy was first identified, there has been considerable debate on whether cochlear implantation is a viable treatment option for children who have been identified with this disorder. In 2008 an international group of scientists and clinicians with expertise in auditory neuropathy met in Como, Italy, to develop guidelines for the diagnosis and management of children with auditory neuropathy (Northern, 2008). They recommended that cochlear implantation be considered for those children who demonstrate poor progress in terms of speech recognition and language development after an adequate hearing aid trial, regardless of behavioral audiometric thresholds. The Como working group did not define what constitutes an adequate hearing aid trial or give suggestions as to the length of the trial allowing for professional clinical judgment on a caseby-case basis. They also recommended that the term auditory neuropathy spectrum disorder (ANSD) be used as it more appropriately describes this disorder that encompasses several possible sites of lesion. The audiological test battery used for diagnosis of ANSD includes click-evoked auditory brainstem response (ABR) and analysis of otoacoustic emissions (OAEs), when possible. Middle ear muscle reflexes are generally absent or elevated in individuals with ANSD (Berlin et al, 2005, 2010), although this is not one of the defining characteristics of ANSD. Normal functioning of the outer hair cells is indicated by the presence of OAEs and/or the presence of a cochlear microphonic (CM) on either electrocochleography (ECochG) or standard ABR recordings that inverts with stimulus polarity reversal. It should be noted that OAEs need not be present for the diagnosis of ANSD as OAEs may be present at first and then disappear over time (Starr et al, 1996). In spite of the endorsement for cochlear implantation in the new Guidelines for Identification and Manage-

ment of Infants and Young Children with Auditory Neuropathy Spectrum Disorder (Northern, 2008), many clinics are still reluctant to implant children with ANSD, particularly when behavioral hearing evaluations reveal audiometric thresholds consistent with milder degrees of hearing loss. Varying reports of success with cochlear implantation have been reported in the literature. Poor outcomes with implantation were reported in the earliest published studies. Miyamoto et al (1999) reported on a child with ANSD who was implanted at the age of 10.9 yr. This child did not achieve open-set speech recognition; however, given that the subject’s ANSD was secondary to Friedreich’s ataxia, it was suggested by the authors that the progressive nature of his disease may have contributed to his poor outcome. That same year, Rance et al (1999) reported on a child with a profound bilateral sensorineural hearing loss (SNHL) who was implanted at the age of 3 yr, 9 mo. Although the implant provided this child with improvement in his lipreading skills, his performance on the PBK (Phonetically Balanced Kindergarten word list) remained near chance levels after 1 yr of implant use. Follow-up electrically evoked ABR (EABR) indicated that his poor performance was likely because the implant could not generate synchronous auditory nerve activation. Although these two early studies found poor outcomes for two children with ANSD who were implanted, Rance et al (1999) felt that the use of cochlear implants with this population could not be ruled out. In the years following these initial reports, a number of articles have been published indicating that children with ANSD could benefit from cochlear implantation and that short-term outcomes were not significantly different than outcomes for other pediatric implant recipients (Trautwein et al, 2000; Shallop et al, 2001; Buss et al, 2002; Madden et al, 2002; Mason et al, 2003; Peterson et al, 2003; Rodrı´quez-Ballesteros et al, 2003; Jeong et al, 2007). Recently it has been suggested that cochlear implantation should be considered the standard of care for children with ANSD who have demonstrated poor progress in speech understanding and spoken language development after a trial of appropriately fitted hearing aids (Joint Committee on Infant Hearing, 2007; Northern, 2008). When children with ANSD are implanted, parents often ask if their child’s outcomes will be comparable to children with SNHL who receive cochlear implants.


Cochlear Implantation in Children with ANSD/Breneman et al

The reports in the literature have not definitively answered this question. Rance and Barker (2008) completed a prospective study of 20 children with ANSD, 10 of whom were implanted and 10 of whom were fitted with binaural hearing aids. They compared speech perception outcomes for both groups of ANSD subjects to a control group of 10 age-matched children with SNHL who were implant recipients. They found that 9 of 10 children with ANSD who were implanted demonstrated significant improvement in their speech perception skills over the pre-implant condition, but they did not perform as well as the SNHL group, and furthermore, they did not do any better than children with ANSD who were fitted with hearing aids. Their results suggested that expectations following cochlear implantation may need to be lower for the ANSD population than for patients with SNHL Teagle et al (2010) conducted a prospective study of 52 children with ANSD who had received an implant in the affected ear. The mean age at implantation was 46.7 mo with a range of 12 to 213 mo. Of the 52 children with cochlear implants, 26 were old enough and without development delays to allow for open-set speech perception testing. For this group of 26 children, the mean postoperative speech perception performance for the PBK was 54% words (range of 4–100%) and 76% phonemes (range of 24–100%). For those children with greater than 6 mo of implant experience but who were either too young or developmentally delayed to complete formal speech perception testing, significant auditory progress was demonstrated on the Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) parental questionnaire with the mean score improving from 26 to 79%. Although there was a considerable range of postoperative performance shown on both IT-MAIS and on PBK word and phoneme recognition, Teagle et al (2010) reported that children with ANSD who are not making auditory progress with amplification—and who do not have cochlear nerve deficiency1—will demonstrate benefit from cochlear implantation. They also reported that robust responses on electrically evoked compound action potentials (ECAP) testing were associated with the development of open-set speech perception skills, and absent or atypical responses were associated with poor implant performance. There are still many questions to be answered regarding cochlear implantation for children with a diagnosis of ANSD. Clinicians are unsure as to how to counsel parents and families regarding realistic expectations and often feel the need to use guarded optimism relative to the prospect of achieving a completely auditory-oral communication mode. To date, Mayo Clinic in Rochester has implanted 53 children with ANSD and over 200 children with SNHL. The earliest outcomes for these children with ANSD and cochlear implants were reported by Shallop et al (2001) and

Peterson et al (2003). The purposes of the current retrospective study were to (1) assess whether children with ANSD who have cochlear implants achieve similar outcomes with respect to speech recognition as matched peers with SNHL when followed over time, and (2) serve as follow-up on a previously published study on 10 children (Peterson et al, 2003). Since that publication 7 yr ago, we have continued to collect longitudinal data on the initial 10 subjects with ANSD and have also added 25 additional subjects for analysis. Approval from the Mayo Clinic institutional review board was obtained for this study. MATERIALS AND METHODS Diagnosis of ANSD Our audiological test battery for pediatric patients includes ABR, OAEs, and immittance measurements, as well as behavioral audiometry and speech perception tests when possible. To identify ANSD, a click-evoked ABR is administered at 90 dB nHL under natural sleep or using conscious sedation. A diagnosis of ANSD is made when the ABR shows absent or markedly abnormal peaks and evidence of a preneural response as shown by the presence of cochlear microphonics that invert with inversion of the stimulus polarity (condensation and rarefaction tracings). In order to rule out stimulus artifact, a diagnosis was confirmed using procedures reported by Rance et al (1999). In particular, the sound tubing coupling the transducer to the insert eartip was disconnected; if the cochlear microphonic disappear, ANSD is confirmed whereas if the “microphonic” remains, it is considered stimulus artifact. Diagnostic imaging of the auditory system using either MRI or high-resolution computed tomography (HRCT) was part of the routine assessment completed by the physicians on our implant team. MRI has been included in our pre-implantation protocol for pediatric implant candidates with ANSD since approximately 2001 and is used to rule out cochlear nerve deficiency (CND), which may present as ANSD on the ABR (Buchman et al, 2006; Walton et al, 2008; Roland et al, in press). Implant Candidacy All children being seen for cochlear implant evaluation are monitored closely by members of the implant team to assess their progress in auditory and spoken language skills. Cochlear implantation is recommended for children with severe-to-profound hearing loss, speech perception scores #30 % on the Multisyllabic Lexical Neighborhood Test (MLNT) or Lexical Neighborhood Test (LNT) in the best aided condition for those able to complete this testing, and/or lack of progress in auditory and spoken language skills after a 3 to 6 mo hearing



aid trial (per Cochlear Americas package insert listing the FDA [Food and Drug Administration] labeling indications). Insufficient progress in auditory and spoken language skills was defined as progress less than the rate of maturation when compared to peers who have normal hearing. For children with ANSD, audiometric thresholds are not the primary consideration in determining candidacy as some had more moderate levels of hearing loss. With these children we look more closely at the rate of progress in auditory and spoken language skills. Subjects Since 1997, our facility has evaluated 62 children with ANSD. Of this group, 53 have received cochlear implants; seven children continue with hearing aids or are still involved in the hearing aid trial; and two children seen for a second opinion have returned to their local clinic for management and follow-up. Outcomes of cochlear implantation for the first five and ten children with ANSD who were implanted at our facility were reported by Shallop et al (2001) and Peterson et al (2003), respectively. These first children have now been using their cochlear implants for up to twelve years. Of the 53 children with ANSD who have received cochlear implants, 35 met the criteria for inclusion in the study. Criteria for inclusion included a diagnosis of ANSD without cochlear nerve deficiency, sufficient cognitive ability to participate in age-appropriate speech perception tests, and English as the first language. Of the 18 patients with ANSD who were excluded, four transferred care back to their local clinic, and one did not return for follow-up. The remaining 13 excluded patients had significant medical/learning comorbidities that impacted their ability to participate in speech perception testing, had atretic auditory nerves, or were bilingual with English as a second language. See the “Discussion” section for further information on these 13 students. The 35 children with ANSD were then matched with 35 implanted children with SNHL who met the same criteria for inclusion. Children with progressive SNHL were excluded. Hearing aids for all children were fit using real ear measurements and the Desired Sensation Level method (DSL v5.0) prescriptive hearing aid fitting formula (Seewald et al, 2005). No child with ANSD showed evidence of spontaneous improvement in hearing prior to implantation when monitored over time by repeat ABR and/or behavioral audiological testing. Demographic information for the 35 children with ANSD and the 35 children with SNHL who met criteria for inclusion in this retrospective review are shown in Tables 1 and 2, respectively. As indicated in these tables, 15 of the children or 43% in the ANSD group were female while in the SNHL group 18 of the children or 51% were female. In the ANSD group, subjects 5 and

7, subjects 19 and 21, and subjects 33 and 34 are sibling pairs. Two children (subjects 1 and 11) had confirmed unilateral ANSD and were implanted in the affected ear. Hearing loss was present at birth for all subjects with the exception of four children with SNHL (subjects 14, 16, 21, and 29) who had meningitis between 3 and 34 mo of age. The comorbidity rate for the children in the current study was 37 and 26% for the ANSD and SNHL groups, respectively. Specific comorbidities presented by each child are listed in Tables 1 and 2. In order to examine whether the rate of comorbidity differed across the ANSD and SNHL subjects, a Mann-Whitney/ Wilcoxon rank sum test was completed that revealed no significant difference across the groups (U 5 542.50, p 5 0.30). In the ANSD group 23 were implanted unilaterally, 11 sequentially, and 1 simultaneously. In the SNHL group, 17 were implanted unilaterally, 14 sequentially, and 4 simultaneously. Of the unilateral CI users, four children from each group continue to use a hearing aid on the nonimplanted ear and are thus bimodal listeners. Four children in the ANSD group (subjects 6, 13, 25, and 31) and three children in the SNHL group (subjects 5, 7, and 24) were implanted with an Advanced Bionics device. All other subjects have a Cochlear Corporation device. In the SNHL group, 80% of the children (28 of 35) are considered auditory/oral, and in the ANSD group, 71% of the children (25 of 35) use auditory/oral language. ANSD subject 26 was counted as an oral communicator even though a PECS (Picture Exchange Communication System) is used when needed because of expressive communication limitations due to autism. Subjects with ANSD and SNHL were matched on variables including age at initial activation of the cochlear implant and months of implant use at test point. As seen in Table 3 the mean age at initial activation for the ANSD group was 38.5 mo (range of 12 to 120 mo) and 39.9 mo (range of 10 to 121 mo) for the SNHL group. Mean months of implant use at the test point for the ANSD group was 70.9 (range of 6–143 mo) and 70.7 for the SNHL group (range of 7–143 mo). Using a one-way analysis of variance, there was no significant difference between the two subject groups in terms of age at implantation (F(1, 68) 5 0.05, p 5 0.81) nor for age at testing point (F(1, 68) 5 0.00, p 5 0.99). In addition, an attempt was made to match subjects on the basis of bimodal, unilateral, simultaneous, or sequential implantation when possible. This secondary match was successful for 49% of the subjects (17 of the 35 subject pairs). Postoperative Electrophysiologic Assessment As part of our cochlear implant protocol, ECAP are measured intraoperatively to verify the synchronous activation of the auditory nerve fibers by electrical stimulation. These measurements are obtained using Neural



Table 1. Subject Details for Children with ANSD Subject

Gender

Risk Factors

1 2

F F

3 4 5 6 7

M F F M F

8 9

M M

10 11 12

M M M

13 14

M F

Unilateral AN, jaundice 28 wk, jaundice, phototherapy, twin None Genetic ANSD, jaundice Genetic ANSD 26 wk Genetic ANSD, jaundice, phototherapy Hospitalized at 11 mo 35 wk, jaundice, NICU, ventilator None Unilateral AN, none 27 wk, ,2 lbs, NICU, ventilator None CMV, lissencephaly

15 16 17

F M M

Premature 32 wk, 3 lbs, ventilator 26 wk, NICU, ventilator

18 19

M F

20

M

21 22 23

F F M

24 25 26 27

M M F F

28 29 30

M M M

31

M

32

F

33 34 35

M F F

Hospitalized at 1 mo Genetic ANSD, jaundice, ventilator 34 wk, jaundice, phototherapy, NICU, ventilator Genetic ANSD Unknown, adopted Jaundice, transfusion, NICU, ventilator Kernicterus Kernicterus Jaundice Jaundice, exchange transfusion, triplet None 35 wk, jaundice, ventilator 36 wk, jaundice, ventilator, seizures, ototoxic 36 wk, jaundice, phototherapy 30 wk, jaundice, transfusion Otoferlin Otoferlin Hemiparesis, seizures

Comorbidity

Implant Condition

Electrode R/L

Mode Home/School

None None

Bimodal U

L: CI512 R: C124RE(CA)

AO TC

Behav disorder None None None None

U U Bimodal Sim U

C124RE(CA)/CI512 R: C124RE(CA) L: C124REwID HiFocus/HiFocus L: 124RE(CA)

TC/AO AO AO/TC AO AO

None ADD

U U

R: C124R(CS) R: C124RE(CA)

AO/TC AO

None None None

Seq, R first Bimodal U

C124RE(CA)/C124RE(CA) L: C124RE L: C124R(CS)

TC AO AO

None Behav disorder, DD None None LD

Seq, R first Bimodal

HR 90k/Helix HiFocus L: 124R(CA)

AO TC

U U Seq, R first

AO Cued Sp AO

None None

U U

R: C124R(CS) R: C124RE(CA) C124R(CS)/ C124R(CA) R: C124R(CS) R: C124M

ADD, seizures, LD, motor delays, apraxia None Mild apraxia None

U

R: C124R(CS)

TC

U U Seq, R first

L: C124M R: C124R C124R(CS)/C124RE

AO Cued Sp AO

CP, dysarthria CP Autism, Usher None

Seq, R first Seq, R first U Seq, R first

C124R/C124REwID HiFocus/HR 90k R: C124R C124R(CS)/C124RE(CA)

AO AO AO/PECS AO

None LD None

U U U

R: C124R(CS) R: C124M R: C124R(CS)

ASL AO AO

None

Seq, L first, L failed Seq, L first

HR 90k/HR 90k

AO

C124M/C124R(CS)

AO/TC

Seq, R first Seq, R first U

C124M/C124RE C124M/C124RE(CA) L: C124M

AO AO AO

Autism spectrum, DD Apraxia None DD, CP, ADD

AO/TC AO

Note: ADD 5 attention deficit disorder, AO 5 auditory oral, ASL 5 American Sign Language, CMV 5 cytomegalovirus, CP 5 cerebral palsy, DD 5 developmental delay, LD 5 learning disorder, PECS 5 Picture Exchange Communication System, Seq 5 sequential, Sim 5 simultaneous, TC 5 Total Communication, U 5 unilateral. Low birth weight 5 ,1500 g, full term 5 $37 wk.

Response Telemetry (NRT), Neural Response Imaging (NRI), or Auditory Nerve Response Telemetry (ART) software from Cochlear Corporation, Advanced Bionics, or MED-EL respectively. ECAP responses were character-

ized as robust, atypical, or absent as described by Teagle et al (2010). ECAP test results are reported for all of the children with ANSD. For all of the 35 children with ANSD who are part of the matched pairs, ECAP



Table 2. Subject Details for Children with SNHL Subject

Gender

Cause/Risk Factors

Comorbidity

1 2 3

F F F

Unknown Unknown Genetic, jaundice, transfusion CMV Unknown

4 5

M M

6

F

7 8 9 10 11 12 13 14

F F F F M M M F

Connexin 26, Family history Genetic Hereditary CMV Unknown Connexin 26 Unknown Connexin 26 Meningitis at 14 mo

15 16 17 18 19

M M F F M

Connexin 26 Meningitis at 34 mo Pendred’s Hereditary Inner ear malformations

20 21 22 23 24 25 26 27 28 29 30 31

F M F F F M M M M F M F

Unknown Meningitis at 15 mo Unknown Unknown Family history Genetic Unknown Genetic Unknown Meningitis at 3 mo Connexin 26 and 30 Unknown

32 33 34 35

M F M M

Triplet Genetic Unknown Waardenburg

Implant Condition

Electrode R/L

Mode Home/School

Torticollis None None

Sim U Sim

Cl512/Cl512 C124RE(CA) C124RE(CA)wlD/C124RE(CA)

AO AO AO

None Cortical dysplasia, motor delays LD

U Seq, R first

R: C124RE(CA) HiFocus/HiFocus

AO AO

U

C124RE

AO/TC

None None None None None None None Behavior disorder Motor delays None None None None

U Seq, L first Seq, L first Sim Sim Bimodal Seq, R first Bimodal

R: HR 90k C124RE(CA)/C124RE(CA) C124RE(CA)/C124R(CS) C124RE(CA)/C124RE(CA) C124RE/C124RE R: C124RE(CA) C124R(CS)/C124RE(CA) L: C124RE(CA)

AO AO ASL AO AO AO AO AO

Seq, R first Bimodal Seq, R first Bimodal Seq, R first, L failed Seq, L first U U, R failed Seq, R first U Seq, R first U U U Seq, L first U Seq, R first

C124RE/C124RE R: C124R C124R(CS)/C124RE R: C124R(CS) C124R(CA)/C124RE(CA)

AO AO AO AO AO/TC

C124RE(CA)/C124R(CS) C124M R: C124R(CA) C124R(CS)/C124REwlD R: HiFocus C124R(CS)/C124RE(CA) R: HiFocus positioner R: C122M R: C124M C124RE/C124M R: C124R(CS) C124/C124RE(CA)

AO AO TC AO AO AO AO AO/TC TC/ASL AO AO AO

Seq, L first U Seq, R first U

C124RE/C124M R: C124m C124RE(CA)/C124REwlD L: C122M

AO AO/TC AO AO

None None None None LD None LD None None None None Autism spectrum None None None DD

Note: AO 5 auditory oral, ASL 5 American Sign Language, CMV 5 cytomegalovirus, DD 5 developmental delay, LD 5 learning disorder, Seq 5 sequential, Sim 5 simultaneous, TC 5 Total Communication, U 5 unilateral.

responses were described as robust. For the 13 ANSD students who were excluded from the study, ECAP responses were described as robust for eight children, atypical for all three of the children with atretic auditory nerves, and atypical for two children with global developmental delays. Speech Perception Tests Because speech perception skills are age dependent and influenced by a child’s vocabulary and language lev-

els, speech perception tests in our battery were administered in a hierarchical order and selected so that they were developmentally appropriate. The first set of tests included in our hierarchical test battery include questionnaires such as the Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) (Zimmerman-Phillips et al, 2000), Meaningful Auditory Integration Scale (MAIS) (Robbins et al, 1991), or the LittlEARS Auditory Questionnaire (Ku¨hn-Inacker et al, 2003), followed by the Early Speech Perception Test (ESP) (Moog and Geers, 1990) and the Glendonald Auditory Screening



Table 3. Age at Initial Stimulation and Duration of CI Use at Test Point for the 35 Individual Subject Pairs with ANSD and SNHL Age at Initial Stimulation Subject 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 Mean SD

AN (mo) 14 43 17 26 18 44 34 49 83 19 14 81 12 49 34 48 18 120 61 19 30 69 13 37 17 15 39 70 51 16 32 30 43 54 27 38.5 24.4

SNHL (mo) 10 46 16 26 22 51 43 56 83 19 11 86 11 58 30 55 23 121 63 20 30 73 13 39 16 20 30 76 64 15 24 22 47 51 25 39.9 26.2

Months of CI Use at Test Difference 4 3 1 0 4 7 9 7 0 0 3 5 1 9 4 7 5 1 2 1 0 4 0 2 1 5 9 6 13 1 8 8 4 3 2 4 3

Procedure (GASP) words and sentences (Erber, 1982). Depending upon the intelligibility and/or vocabulary level of the child, we may then progress to the second set of tests in our battery and administer closed-set tests such as the Northwestern University-Children’s Perception of Speech (NU-CHIPS) (Elliot and Katz, 1980) or the Word Intelligibility by Picture Identification (WIPI) Test (Ross and Lerman, 1970), or advance to open-set tests such as the MLNT (Kirk et al, 1995), LNT (Kirk et al, 1995), and Consonant Nucleus Consonant (CNC) word lists (Peterson and Lehiste, 1962). Both the MLNT and LNT tests contain lists of “easy” and “hard” words. Easy words are words that occur often in the language and have few phonemically similar words with which they can be confused. Hard words are words that occur less often and have many phonemically similar words

AN (mo) 6 8 9 16 26 31 35 36 37 39 48 50 61 62 65 65 66 71 77 78 84 86 87 89 90 91 96 106 108 120 109 111 139 135 143 70.9 38.0

SNHL (mo) 7 14 10 15 30 31 31 32 37 36 56 43 66 45 54 69 70 74 64 83 95 88 81 99 85 94 100 109 102 114 116 114 135 133 143 70.7 38.3

Difference 1 6 1 1 4 0 4 4 0 5 8 7 5 7 11 4 4 3 13 5 11 2 6 10 5 1 4 3 6 6 7 3 4 2 0 5 3

with which they can be confused. Recorded sentence materials include the Hearing-in-Noise Test for Children (HINT-C) (Gelnett et al, 1995) and AzBio sentences (Spahr and Dorman, 2005). When possible, we also test the child’s sentence recognition in noise using the BKB-SIN (Bamford-Kowal-Bench Sentences in Noise) (Bench et al, 1979). Sentence materials in quiet and in noise were not included in the analysis. With the exception of the questionnaires, all speech perception tests described in the current study were administered in a double-walled sound booth. The ESP, GASP words, GASP sentences, NU-CHIPS, and WIPI were administered via monitored live voice with a stimulus presentation level of 60 dBA that was calibrated with a Larson Davis LxT sound level meter placed in the control room with the pre-amp and microphone permanently affixed



in the sound booth via extension cable. The position of the microphone is located directly above the patient’s head and can be vertically adjusted based on patient height. The remaining tests were administered using recorded materials also with a calibrated presentation level of 60 dBA. Each child’s sound processor was adjusted to typical use settings prior to testing. RESULTS Audiometric Thresholds Preoperatively, all subjects’ audiograms demonstrated considerable symmetry across ears. A two-way ANOVA was completed with ear and subject group as the independent variables and three-frequency pure tone average (PTA) of 500, 1000, and 2000 Hz as the dependent variable. There was no effect of ear either collapsed across subject group (p 5 0.51) or within a subject group (p 5 0.50) on the preoperative PTA. There was, however, a significant difference across groups on preoperative PTA (F(1,138) 5 16.71, p , 0.001) with the ANSD subjects demonstrating significantly lower, that is, better, preoperative thresholds. Preoperatively, mean PTA collapsed across ear was 83.8 and 97.7 dB HL for the ANSD and SNHL groups, respectively. This is not an unexpected finding given that patients with ANSD often exhibit disproportionately low (i.e., good) audiometric thresholds when considering the poor speech recognition and auditory progress that typically accompanies this diagnosis. Postoperatively, mean cochlear implant soundfield audiometric thresholds in response to warbled pure tones obtained on the day of testing ranged from 19 to 26 dB HTL for 250 through 6000 Hz for both groups. Statistical analysis revealed no significant difference in implant only soundfield audiometric thresholds across the groups (t 5 21.22, p 5 0.23). Internal Device Status All but one child had full insertion of the electrode array. This child (SNHL subject 19) has six extracochlear electrodes on his right internal device due to the inner ear malformations, and thus these electrodes have been deactivated. For all but one subject in the ANSD group, there was no evidence of more than one open circuit or pair of short-circuited electrodes during surgery. Subject 13 in the ANSD group currently has 4 open electrodes on his left device. Three of these four electrodes were identified as being open circuits during surgery; however, given the robust neural potentials recorded from the other 13 electrodes it was determined that having three open electrodes immediately upon insertion was likely due to the presence of intracochlear air bubbles. Later it was found that this was not the

case. Given that this child has exhibited high levels of performance without any evidence of degradation since surgery, neither his family nor the cochlear implant team has been willing to consider revision at this time. Subject 31 in the ANSD group had his internal device replaced due to device failure, and two children in the SNHL group (subjects 19 and 22) have each had one internal device replaced due to failure. In all cases, the time between device failure and device replacement was short (1.5–2 mo), and each child was able to reach or exceed previous performance levels within a few months.

Speech Recognition Performance As stated in the “Methods” section, monosyllabic word recognition was assessed via the LNT or CNC metric. Although we were able to obtain scores on the same metric for most subject pairs, given the nature of a retrospective study, there are some subject pairs for whom the same metric was not administered. Thus we completed a secondary prospective study in which monosyllabic word recognition data were obtained from 40 pediatric cochlear implant recipients for whom both LNT-Hard and CNC word scores were administered in a single test session. Mean age for these subjects was 9.6 yr with a range of 7.3 to 16.3 yr. For these 40 subjects, the mean monosyllabic word recognition scores were 75.6% (SD 5 16.1) and 75.3% (SD 5 16.7) for the LNT-Hard and CNC words, respectively. A one-way, repeated-measures ANOVA revealed no significant difference between LNT-Hard and CNC word recognition scores [F(1, 39) 5 0.04, p 5 0.84]. Thus, it was determined that monosyllabic word recognition on either LNT-Hard or CNC would be plotted and analyzed as one monosyllabic word recognition metric. Figure 1 displays scores for monosyllabic stimuli on either the LNT-Hard or CNC metrics, and Figure 2 displays scores for multisyllabic stimuli on the MLNT lists. Focusing first on monosyllabic word recognition shown in Figure 1, mean performance was 83.5% (SD 5 9.6) for the ANSD group and 76.5% (SD 5 15.3) for the SNHL group. Also shown in Figure 1, there are a few subject pairs for which one subject in the pair is lacking a monosyllabic word recognition score. Thus, examining just those 22 subject pairs for which all subjects have completed monosyllabic word recognition testing with either LNT-Hard or CNC, mean scores were 83.2% (SD 5 9.1) and 77.0% (SD 5 15.8) for the ANSD and SNHL groups, respectively. A Kruskal-Wallis one-way ANOVA on ranks was completed for the monosyllabic word recognition data as the dataset failed to meet the assumption of equal variance. This analysis revealed no difference in monosyllabic word recognition between the ANSD and SNHL subjects (H(1) 5 1.15, p 5 0.28).



Figure 1. Performance of matched subject pairs on either the LNT-Hard or CNC word metrics in percent correct. Mean performance was 83.5% for the ANSD group and 76.5% for the SNHL group. When examining the 22 subject pairs who both completed monosyllabic word recognition testing, mean scores were 83.2 and 77.0% for the ANSD and SNHL groups, respectively. Error bars represent 61 standard deviation.

Multisyllabic word recognition data for individual subjects as well as the mean are shown in Figure 2 for the MLNT-Easy or MLNT-Hard metric. For a given subject pair, data were plotted only if both subjects were administered the MLNT with the same level of difficulty (either MLNT-Easy or MLNT-Hard). Mean multisyllabic

word recognition performance was 81.3% (SD 5 13.2) for the ANSD group and 78.0% (SD 5 18.3) for the SNHL group. Also shown in Figure 2, there are a few subject pairs for which one subject in the pair is lacking a monosyllabic word recognition score. Thus, examining just those 24 subject pairs for which all subjects have

Figure 2. Performance of matched subject pairs on the MLNT-Easy or MLNT-Hard metrics in percent correct. For a given subject pair, data were plotted only if both subjects were administered the MLNT with the same level of difficulty (either MLNT-Easy or MLNT-Hard). Mean multisyllabic word recognition performance was 81.3% for the ANSD group and 78.0% for the SNHL group. Error bars represent 61 standard deviation.



completed multisyllabic word recognition testing, mean scores were 80.5% (SD 5 11.6) and 78.3% (SD 5 18.3) for the ANSD and SNHL groups, respectively. A KruskalWallis one-way ANOVA on ranks was completed for the monosyllabic word recognition data as the dataset failed to meet the assumption of equal variance. This analysis revealed no difference in monosyllabic word recognition between the ANSD and SNHL subjects (H(1) 5 0.01, p 5 0.93). When reviewing monosyllabic and multisyllabic test scores displayed in Figures 1 and 2, it is seen that 80% of the subjects in the ANSD group (28 out of 35) and 69% in the SNHL group (24 out of 35) achieved open-set word scores of 80% or better. Of the children unable to complete either multisyllabic or monosyllabic word tests, ANSD subjects 1, 3, and 5 had only been implanted for 9 mo or less. ANSD subject 5 has used her device for 26 mo but has not made progress in her auditory skills. In the SNHL group, subjects 1, 3, and 4 have used their device for 15 mo or less, and subjects 9 and 28 are now using American Sign Language as their primary mode of communication. Looking at only the 60 children who were 5 yr or older at time of testing (subject pairs 6 through 35), all subjects in both the ANSD and SNHL groups were able to complete either multisyllabic (n 5 57) and/or monosyllabic (n 5 53) word testing with the exception of the two SNHL subjects who now communicate using American Sign Language. The ability of these patients to complete open-set word testing is consistent with previous research that indicates that children with normal hearing can achieve scores near ceiling on the MLNT and LNT at the age of 3 yr or older (Kluck et al, 1997) and that most children implanted around the age of 2 yr can be evaluated by the MLNT/ LNT by their 24 mo follow-up visit (Wang et al, 2008). There were eight subject pairs for whom either incomplete or no data were available for either multisyllabic or monosyllabic words (subject pairs 1, 3, 4, 5, 9, 20, 26, and 28). GASP word recognition performance was available for subject pairs 4, 20, and 28 and is shown in Table 4. Statistical analysis revealed no difference between GASP word recognition performance for

the ANSD and SNHL subjects (t 5 20.25, p 5 0.82). For four subjects pairs (1, 3, 5, and 26), auditory questionnaire data were obtained and are displayed in Table 4. A t-test was completed on the raw data obtained for the LittlEARS questionnaire for subject pairs 1, 3, and 5. As with all other metrics, there was no difference between the ANSD and SNHL subjects in terms of hearing age as evidenced by LittlEARS (t 5 0.58, p 5 0.59). No matching tests were administered to subject pair 9. For the last remaining subject pair 26, a MAIS score of 98% was obtained for both subjects. DISCUSSION

R

esults of this study demonstrate that many children with ANSD can clearly benefit from cochlear implantation and that their long-term outcomes are similar to matched peers with SNHL on measures of speech recognition. Of the 35 children with ANSD who were implanted, 32 (91%) have achieved some degree of open-set word recognition ability. Analysis of speech perception scores for matched pairs indicates no significant difference between the ANSD and SNHL groups on any of the assessed measures. Mean scores on the MLNT-Easy and MLNT-Hard metrics were 80.5 and 78.3% for the ANSD and SNHL groups, respectively. Mean scores on the LNT-Hard and/or CNC metrics were 83.2 and 77.0% for the ANSD and SNHL groups. For the subject pairs for whom incomplete data were available for the monosyllabic and/or multisyllabic words, equivalent performance was found on either the GASP word test or on auditory questionnaires. For the three ANSD children who were unable to complete the recorded word tests, two children had been implanted for 9 mo or less, and the remaining child (subject 5) 2, who was not making progress as expected, used her device for 26 mo. Overall findings in this study are consistent with a number of previous studies showing excellent progress following cochlear implantation for children with ANSD (Trautwein et al, 2000; Shallop et al, 2001; Buss et al, 2002; Madden et al, 2002; Mason et al, 2003; Peterson et al, 2003; Rodrı´quez-Ballesteros et al, 2003; Jeong

Table 4. Scores on GASP Words and Auditory Questionnaire Test Results for Matched Subject Pairs Unable to Complete Monosyllabic or Multisyllabic Word Tests Subject Pairs 1 3 4 5 20 26 28

GASP words (% correct) ANSD

LittlEARS (out of 35 possible)

SNHL

100

83

90

96

50

58

ANSD

SNHL

35 32

21 32

29

35


MAIS (% correct) ANSD

SNHL

98

98


et al, 2007; Berlin et al, 2010). In addition, robust ECAP measurements were obtained for all 35 ANSD subjects, which is consistent with development of open-set word recognition abilities (Teagle et al, 2010). The results of the current study are in contrast to those reported by Rance and Barker (2008). They reported that although implants can provide open-set speech perception abilities for most of the ANSD children who are implanted, expectations may need to be lower for this group than for children with SNHL. Specifically, they reported that (1) children with SNHL who were implanted demonstrated significantly better phoneme recognition than children with ANSD who were also implanted, and (2) children with ANSD who were implanted did not do any better than children with ANSD who were fitted with hearing aids. Rance and Barker (2008) pointed out that the results for the aided group were biased in that the children with ANSD who were successful with hearing aids represented the top performers since the children with ANSD who performed poorly with hearing aids were eventually implanted. Another difference between these two studies may be in comorbidities. Rance and Barker (2008) reported that 8 of the 10 children with ANSD who received cochlear implants had a “rocky neonatal course” that could have impacted results for that group, but they did not specify possible comorbidities in each group. In the current study there was no significant difference in the overall rate of comorbidity between groups. In addition, the number of subjects was higher in this study than in the Rance and Baker study, which may have influenced outcomes between the two studies. Thirteen children with ANSD received cochlear implants but did not meet criteria for inclusion in this study. Because they are part of the larger population of children with ANSD identified at our center, it is important to also review their progress with implantation. Of the excluded children nine had significant learning or medical issues (global developmental delay, autism, cerebral palsy, and/or tracheotomy) that precluded participation in standard speech perception tests; one child used English as the second language; and three children had atretic auditory nerves. For the children in this study with significant cognitive and global developmental delays, the implant provides awareness of sound and improved quality of life according to the parents. One patient with Usher syndrome and autism was implanted at the age of 9 yr. His implant provides him with auditory awareness and connection to his environment, which is beneficial as his vision decreases. The other child with autism has good receptive skills with his implant, but expressively he remains dependent upon PECS and sign language for communication. The overall comorbidity rate for the 60 children with ANSD evaluated at this facility was 45% (27 of 60), which is just slightly above the expected rate of 40% for children with SNHL (Gallaudet Research Institute, 2008). It is our experience that the

children with ANSD who have multiple disabilities or other learning issues that impact success with a cochlear implant make progress at a rate that would be expected in a child with SNHL who faces the same challenges when neural synchrony can be restored. Although the 35 children with ANSD in this study have achieved similar outcomes following implantation in speech recognition abilities as matched peers with SNHL, it is recognized that children with ANSD are a heterogenous group in reference to site of lesion, age at identification and implantation, comorbidities, and status of the auditory nerve. Therefore, cochlear implantation may not be appropriate for all children with ANSD. Five children (8%) on our caseload have made ongoing progress with hearing aids. This percentage is significantly lower than the approximate 30–50% success rate with hearing aids as reported in previous studies (Rance et al, 2002; Teagle et al, 2010) likely because we are located in a rural setting and most of our patients come from a five-state area. Our numbers may be biased in that children with ANSD who are referred to our facility for evaluation as possible candidates for cochlear implantation will not include those children who are making progress with hearing aids. When assessing CI candidacy in the ANSD population, it is also important to identify CND, which will negatively impact progress. Four children (6%) were identified with absent auditory nerves and were not implanted. Although analysis of ECAP testing was not the purpose of this study, all 35 matched children with ANSD had normal ECAP morphology. Of the excluded subjects, four children had abnormal ECAP waveforms. These four children did not develop open-set speech perception skills, which is consistent with previous studies (Rance et al, 1999; Gibson and Sanli, 2007; Rance and Barker, 2008; Walton et al, 2008; Teagle et al, 2010) that show a correlation between electrophysiological results such as ECAP and EABR and outcomes with cochlear implantation. Normal EABRs and robust ECAP measurements are associated with better outcomes from implantation. Because these measures reflect an intact auditory pathway at the level of the brainstem and do not measure higher cortical responses, the presence of normal EABR/ECAP measurements does not guarantee success with implantation. Future research that may be helpful in management of children with ANSD might include the impact of the amount of residual hearing in the nonimplanted ear for those children who are implanted unilaterally and the influence of preserved hearing in the implanted ear following soft surgical techniques. CONCLUSIONS

T

he results of this study clearly demonstrate that children with ANSD who have cochlear implants



achieve similar outcomes with respect to speech recognition as matched peers with SNHL. Analysis of speech perception scores on multisyllabic and monosyllabic word lists for matched pairs indicated no significant difference between the ANSD and SNHL groups. Those children who were unable to participate in recorded word tests showed equivalent progress on either the auditory questionnaires or on the GASP word test. Although some children with ANSD can make progress with hearing aids, it is our recommendation that cochlear implantation be considered for those children with ANSD who have normal auditory nerves and who demonstrate poor progress in auditory, speech, and language development following trial use of hearing aids. If additional disabilities or learning issues are present, it is important to counsel parents regarding realistic expectations.

260 patients with auditory neuropathy/dys-synchrony (auditory neuropathy spectrum disorder). Int J Audiol 49:30–43. Berlin CI, Hood LJ, Mortlet T, Wilensky D, St. John P, Montgomery E, et al. (2005) Absent or elevated middle ear muscle reflexes in the presence of normal otoacoustic emissions: a universal finding in 136 cases of auditory neuropathy/dys-synchrony. J Am Acad Audiol 16:546–553. Buchman CA, Roush PA, Teagle HFB, Brown CJ, Zdanski CJ, Grosse JH. (2006) Auditory neuropathy characteristics in children with cochlear nerve deficiency. Ear Hear 27:399–408. Buss E, Labadie RF, Brown CJ, Gross AJ, Grose JH, Pillsbury HC. (2002) Outcome of cochlear implantation in pediatric auditory neuropathy. Otol Neurotol 23:328–332. Elliot LL, Katz D. (1980) Northwestern University-Children’s Perception of Speech (NU-CHIPS) Test. St. Louis: Auditec. Erber NP. (1982) Auditory Training. Washington, DC: AG Bell Association for the Deaf.

NOTES 1. Cochlear nerve deficiency is a condition in which the auditory branch of the eighth cranial nerve is either absent or hypoplastic. In cases of CND, OAEs and the CM are generally present, and thus CND can be misdiagnosed as ANSD (Buchman et al, 2006; Walton et al, 2008; Roland et al, in press). 2. ANSD subject 5 achieved pattern perception skills on the ESP after two years of device use. She was implanted at the age of 18 mo, and full insertion of the device was achieved. Normal imaging was obtained pre-implant and ECAP waveforms obtained during surgery and postimplantation were characterized as robust. Further, all impedances were and continue to be within the range of normal for all 22 intracochlear electrodes in the array. There was no evidence of open or short circuits on any of the electrodes. This child has an older sister with ANSD who was also implanted (subject 7). Although the educational team was inexperienced in working with children who have been implanted, the older sister has shown ongoing and steady progress in her auditory, speech, and language skills with the same educational team and habilitation history. In addition, both girls have a reportedly similar history of device use (at least 12 hr a day or more). Teagle et al (2010) reported that abnormal MRI and atypical or absent ECAP responses are associated with poor performance by children with ANSD who are implanted. In this case, the child’s auditory progress has been slower than expected even though normal imaging and ECAP responses were obtained. It is expected that limited intervention services and less than full-time use of the device all waking hours have played a role in her slow progress. Given that this child was only 3.5 yr of age at the time of her most recent evaluation, it is possible that cognitive issues and/or additional comorbidities that may be affecting outcomes may arise later.

Acknowledgments. The authors would like to thank an anonymous reviewer as well as Dr. Jon Shallop for their helpful comments and suggestions in revising this manuscript.

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