www.bjorl.org
Brazilian
Journal
of
OTORHINOLARYNGOLOGY
ORIGINAL
ARTICLE
Management
of
children
with
auditory
neuropathy
spectrum
disorder
(ANSD)
夽
C
¸a˘
gıl
Gökdo˘
gan
a,∗,
¸enay
S
Altınyay
a,
Bülent
Gündüz
a,
Yusuf
Kemal
Kemalo˘
glu
b,
Yıldırım
Bayazıt
b,
Kemal
Uygur
baGaziUniversityHospital,DepartmentofAudiology,Ankara,Turkey
bGaziUniversityHospital,DepartmentofENT-HNS,Ankara,Turkey
Received8March2015;accepted21August2015 Availableonline18December2015
KEYWORDS
Auditoryneuropathy spectrumdisorders; Sensorineuralhearing loss;
Amplification; Rehabilitaton
Abstract
Introduction:ANSDisachallengingproblem.
Objective: TopresentourexperienceonmanagementofthechildrenwithANSDwithrespect toclinicaldata.
Methods:This retrospective study included all children younger than16 years ofage who applied tothedepartmentbetween 2005and2013(withtheexceptionofnewbornhearing screening NHSreferrals). The data were derivedfrom puretone, OAEs andABR tests, and furthermedicalriskfactorsofthesubjectswereevaluated.
Results:ANSDwasrecognizedin74earsof40children(B/U:34/6)among1952childrenwith SNHL(2.04%)detectedamong 9520applicants tothedepartment (0.42%).Theclinicaltests revealedthathearinglossgreaterthan15dBwaspresentinbothearsof38cases.Thedegree ofhearinglosswasprofoundin48%children,severein12%children,moderatein28%children, mildin10%childrenandnormalin5%children.ABRswereabsent/abnormalin37/3earsand CMsweredetectedinall.Acousticreflexeswereabsentinallears.Rehabilitationwasmanaged by CI andhearing aidsin15 and23 cases,respectively. FMsystem wasgiven totwo cases displayingnormalhearingbutpoorspeechdiscriminationinnoisyenvironments.
Conclusion: ANSDisarelativelychallengingproblemfortheaudiologydepartmentsbecause ofitsvariousclinicalfeaturesanddifficulties inmanagement.Our patientswithANSD most commonlydisplayedprofoundhearingloss.Thenumberofoverlookedcasesmaybeminimized byperformingABRandOAEineverycasereferredwiththesuspicionofhearingloss.
© 2015 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
夽
Pleasecitethisarticleas:Gökdo˘ganC¸,AltınyayS¸,GündüzB,Kemalo˘gluYK,BayazıtY,UygurK.Managementofchildrenwithauditory neuropathyspectrumdisorder(ANSD).BrazJOtorhinolaryngol.2016;82:493---9.
∗Correspondingauthor.
E-mail:cagilgokdogan@gmail.com(C¸.Gökdo˘gan).
http://dx.doi.org/10.1016/j.bjorl.2015.08.022
PALAVRAS-CHAVE
Espectroda
neuropatiaauditiva; Perdaauditiva neurossensorial; Amplificac¸ão; Reabilitac¸ão
Tratamentodecrianc¸ascomespectrodaneuropatiaauditiva(ENA)
Resumo
Introduc¸ão:Espectrodaneuropatiaauditivaaindaéumacondic¸ãoclínicadesafiadora. Objetivo:Apresentarnossaexperiêncianotratamentodecrianc¸ascomespectrodaneuropatia auditivaemrelac¸ãoaosdadosclínicos.
Método: Esteestudoretrospectivoincluiucrianc¸as menoresde16anosdeidadequederam entradanodepartamentoentre2005e2013(comexcec¸ãodeencaminhamentosparatriagem auditivaneonatal).Foramavaliadososdadosobtidosapartirdosexamesdeaudiometriatonal, emissõesotoacústicas(EOA),potencialevocadoauditivodetroncoencefálico(ABR)eoutros fatoresderisco.
Resultados: Das1.952crianc¸ascomperdaauditivaneurossensorial(2,04%)detectadasdentreos 9.520candidatosquederamentradanodepartamento(0,42%),espectrodaneuropatiaauditiva foireconhecida em74 orelhasde40 crianc¸as(B/U: 34/6).Ostestesclínicosrevelaramque uma perdaauditiva superior a15dB estavapresente em ambasas orelhas em 38 casos.O graudeperdaauditivadascrianc¸aseraprofundoem48%,graveem12%,moderadoem28%, leveem 10%,enormal em 5%.ABR estavaausente/anormalem 37/3 orelhase microfonia coclearfoidetectadoemtodasascrianc¸as.Reflexosacústicosestavamausentesemtodasas orelhas.Areabilitac¸ãofoitratadacomimplantecocleareaparelhosauditivosem15e23casos, respectivamente.UmsistemaFMfoiutilizadoemdoiscasosqueapresentavamaudic¸ãonormal, masdiscriminac¸ãodeficientedafalaemambientesruidosos.
Conclusão:Espectrodaneuropatiaauditivaéumproblemadesafiadorparaosdepartamentosde audiologia,devidoàssuasváriascaracterísticasclínicasedificuldadesnotratamento.Emnossos pacientesaperdaauditivaprofundafoiamaisfrequente.Onúmerodecasosnegligenciados podeserdiminuídocomarealizac¸ãodosexamesABReEOAemtodososcasosencaminhados comsuspeitadeperdaauditiva.
© 2015 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Publicado por Elsevier Editora Ltda. Este ´e um artigo Open Access sob uma licenc¸a CC BY (http:// creativecommons.org/licenses/by/4.0/).
Introduction
The hearing loss known asauditory neuropathy spectrum disorder (ANSD) has been described by the presence of otoacoustic emissions despite absent or severely abnor-mal auditory brainstem responses (ABRs).1---3 Foerst etal.
reporteditsprevalence as0.94% and 8.44% for infants at riskforhearingimpairmentandprofoundlyhearingimpaired children,respectively.4Previously,Krausetal.determined
theseratesas1.3%and14%.5
It has been reportedthat ANSD was relatedwith vari-ousclinicalandaudiologicalpatterns.Puretonethresholds (PTAs) rangefromnormal or near normal tosevere hear-ing loss, particularly characterized by impaired auditory processing skills in noisy environments. These subjects presentverylowspeechdiscriminationscores(SDS)which are not associated with the pure tone levels. Acoustic reflexesareabsentinthemajorityofthecases.1,2,6
Ithasbeen reportedthat,particularlybecauseofpoor SDSinrelationtobetterPTAs,managementprocessof chil-drenwithANSDis moreproblematicthanthat ofchildren withotherhearinglosspatterns.7---10Furthermore,sincethe
siteofthelesioninthesubjectsclinicallycollectedintothe ANSDgroupisstillunknown andtherehasnotbeen atest todiscriminatethe lesion site of the givencases,2
selec-tionofthemanagementoptionbecomesmoredifficult.7---10
Majorinterestsatthispointhavebeenfocusedonwhether
the cochlear implant (CI)is beneficialor not inthe given cases.However,insomecases,itcouldevenbedifficultto decidebetweentheoptionsofahearingdeviceand‘‘waiting andactivelyobserving’’.7---10Theacceptedapproachtoward
childrenwithANSDistoinitiallyprovideamplificationusing hearing aids; however, many ANSD patients demonstrate little functional hearing and speech understanding with conventional amplification. In subjects who demonstrate poorspeechunderstandinganddelayedlanguage develop-mentwithhearingaids,cochlearimplantation(CI)maybe offered.2,11
Ourpurposein this study is topresent ourexperience onthemanagementofchildrenwithANSDwithrespectto clinicaldata.
Methods
This study has been done in a retrospective manner and included all children younger than 16 years of age, who appliedtotheaudiologydepartmentbetween2005and2013 (Ethical Committee:446). The subjects werefirst divided intotwosubgroupsaccording topresenceof sensorineural hearingloss(SNHL)(>15dB),11andthentheSNHLgroupwas
The audiological evaluation of patients who are sus-pectedofhavingANSDshouldincludethefollowingcriteria: presenceofCM;abnormalorabsentABR.
The audiometric data of the subjects with ANSD and auditory perception skills --- language development were evaluated.
Audiometrictests
Age-specific pure tone audiometry from 250 to 6000Hz was performed for all subjects using conversional, play or behavioral methods. Speech detection and recognition assessmentsincludedspeechawarenesstest(SAT)for chil-drenandspeechrecognitionthreshold.Tympanometryand acousticreflexevaluationwerealsoperformedatthetime of testing. Acoustic reflexthresholds weremeasured ipsi-lateral andcontralateral withpure tone stimuli from500 to4000Hz. Stimulated earswereconsidered absent when therewasnoresponsetotestintensitiesupto110dBHL.
Otoacousticemissions(OAE)
Clickevokedotoacousticemissionsweremeasuredwithan ILO --- 92 OAE system. The click level ranged from 80 to 86dB peak sound pressure. Responses toas many as260 stimuliwereaveragedovera20mswindowandstoredintwo separatebuffers.Thepresenceofnormaltransientevoked otoacoustic emissions wasdetermined by response ampli-tudeofatleast3dBandwaveformreproducibilityinatleast threeoctavebandsof>75%.
Auditorybrainstemresponse(ABR)
ABRwasrecordedinasingleelectrodeconfiguration,in a channel running from the forehead to the ipsilateral ear using a band-pass filter between 100 and 3000Hz. Click stimuliconsistedofonerunofcondensationfollowedbyone runrarefactionclickspresentedmonaurallyatratesof13.0 persecondandatintensitiesof75dBand,whennecessary, at95dBHL.CMwasdemonstratedbythechangingpolarity inABR. Patientsunderwentassessmentin asoundtreated roominastateofnaturalorchloralhydrateinducedsleep.
Auditoryperceptionskills
Auditoryperceptionskills’evaluationofchildrenwith hear-ingaidsandcochlearimplantswasperformedusingtheLing soundstest,theInfant-ToddlerMeaningfulAuditory Integra-tionScale(IT-MAIS),MeaningfulUseofSpeechScale(MUSS) andLittlEARS.
Lingsoundstestisanauditoryperceptionskillstestandis usedtoevaluateboththedetectionandthediscrimination of sounds. Six picture cards symbolizing the sounds were usedtoevaluatechildrenduringthetest.
TheInfant-ToddlerMeaningfulAuditoryIntegrationScale (IT-MAIS)isamodificationoftheMeaningfulAuditory Inte-grationScale (MAIS). It is astructuredinterview schedule designed to assess the child’s spontaneous responses to soundinhis/hereveryday environment.Theassessmentis baseduponinformationprovidedbythechild’sparent(s)in
responseto10probes. These10probes assessthreemain areas:(1)vocalizationbehavior,(2)alertnesstosounds,and (3)deriving meaningfrom sound.Specific scoring criteria havebeendevelopedforeachofthe10probes.
MeaningfulUseofSpeechScale(MUSS)isaparentreport scale,whichisdesignedtoassessthechild’suseofspeechin everydaysituations.Itconsistsofteninquirieswhichassess thefollowing areas: vocal control,use of speech without gestureorsignanduseofcommunicationstrategiesin every-daysituations.
LittlEARS auditory questionnaire is a parent question-nairedesigned toassess the auditory behavior of hearing impairedchildrenwhoareprovidedwithaCIorahearing aidprior totheir 24thmonth of life. Itrecordspreverbal auditorydevelopmentduringthefirsttwoyearsofhearing in the child’s natural environment, taking into consider-ationreception,understandingandadequateresponseand vocal-verbalproductionofacoustic(linguistic)stimuli.The questionnaireconsistsof35age-relatedsortedquestionsto beansweredwith‘‘yes’’or‘‘no’’byparents.
Languagedevelopmentevaluation
Direct assessment of expression and receptive language measuresincludedthePreschoolLanguageScale,version4 (PLS-4).
Statisticalevaluation
SPSS16.0(SPSS,Inc.,Chicago,IL,USA)wasused.Wilcoxon test was used to compare the auditory perception and languagescores of the patients before and after hearing amplification.
Results
Wefoundthat9520childrenwereevaluatedinthe depart-mentduringthestudyperiodandsensorineuralhearingloss wasrecognizedin1912ofthem(20.08%).ANSDwasfoundin 74earsof40children(male:23;female:17).ANSD preva-lenceinthechildrenpopulationwithsensorineuralhearing losswasfoundtobe1.89%.Theaverageageofchildrenwith ANSDatdiagnosiswasdeterminedas3.05±2.44years.
AsseeninFig.1,factorsthatareknowntobeassociated ANSDwerefoundin19of40children;historyof hyperbiliru-binemiain15%;prematurityin5%;lowbirthweightin5%; genetichistory(siblings)in5%;54%ofchildrenhadnoknown associatedpathologyorriskfactor.
Alloftheearsofthesubjectshadnormaltympanogram anddisplayednoacousticreflexresponse.AsseeninFig.2, thedegree of hearing loss wasprofound in 48% children, severein 12%children, moderatein 28% children,mild in 10%childrenandnormalin5%children.
54%
15% 5% 5%
13%
5% 3%
Etiology
Unknown
Hyperbilirubinemia
Low birth weight
Prematurity
Multifactor
Genetic?
Hematological disorders
Figure1 EtiologicalfactorsofANSDpatients.
Hearing loss degree
Normal
Mild
Moderate
Severe
Profound 48%
5%
10%
25%
12%
Figure2 HearinglossdegreeofANSDpatients.
Amplification
FM
Hearing aids
Cochlear implant 5%
57% 38%
Figure3 AmplificationchoicesofANSDpatients.
Twopatientswhohadnormalhearingweresuggestedto usetheFMsystemforeducation.However,bothparentsof thepatientsdidnotwishtheirchildrentousethem.Thus wedidnotfollowuptheFMsystem’seffectivenessinANSD withnormalhearing(Fig.3).
Twenty-three of the patients were given hearing aids. Twoofourpatientswithhearingaidshadnosufficient ben-efitfromitsuse,buttheywerenotsuggestedimplantation duetotheirage,irregularhearingaiduseandinsufficient rehabilitation.Fifteenofthepatientswithhearingaidsdid notcometofollow-upandrehabilitation.
Fifteen patients with ANSD were suggested cochlear implants and then they were operated on. Intraopera-tiveimpedancemetryandneuralresponsetelemetry(NRT) were within normal limits. None of them had immediate
2.4
0
8.4
5.12
3.3 3.6
0.6
20.25
10.88
16.38
LING (sound detection)
LING (sound discrimination)
IT MAIS MUSS LittlEARS
HA (1stmonth) HA (12thmonth)
Figure4 ResultsofauditoryperceptionskillsscoresinANSD withHA.
0 1 2 3
1
2
1
2
1
3
1 1
Number of patients
Steps of age ranges
Receptive language Expressive language
Figure5 ResultsofPLS-4scoresinANSDwithHA(PLS-4scores wereshownasprogressinagerangebysteps).
postoperativecomplications. Postoperative impedanceme-try andneural responsetelemetry(NRT) werealsowithin normal limits.However,fourof the patients withhearing aidsdidnotcometofollow-upandrehabilitation.
For the evaluation of auditory perception skills LING, ITMAIS,MUSS,and LittlEARSscoreswere determinedone and12monthsafterhearingaidfitting,dependingondata availability. All patients with sufficient follow-up to date demonstrated significant improvementdue tothe hearing aids(p<0.05)(Fig.4).Fortheevaluationoflanguage devel-opment,PLS-4scoresweredeterminedthroughthefittingof hearingaidsoneand12monthsafterthehearing-aidfitting depending ondataavailability.Allpatients withsufficient follow-up to date demonstrated significant improvement duetothehearingaids(p<0.05)(Fig.5).
0.9
0
4.1 3.6
0.36 5
5
32.5
22.3
25.2
LING (sound detection)
LING (sound discrimination)
IT MAIS MUSS LittlEARS
Preop Postop (12th month)
Figure6 ResultsofauditoryperceptionskillsscoresinANSD withCI.
0 1 2 3
1
2
7
1
5
4
Number of patients
Steps of age ranges
Receptive language Expressive language
Figure7 ResultsofPLS-4scoresinANSDwithCI(PLS-4scores wereshownasprogressinagerangebysteps).
ondataavailability.Allpatientswithsufficientfollow-upto date demonstratedsignificant improvement due tothe CI (p<0.05)(Fig.7).However,therewasnodifferenceinthe effectofANSDonoutcomesbetweenthosewhouseHAand thosewhouseCI(p>0.05).
Discussion
ThetermauditoryneuropathywasfirstusedbySiningerand colleaguesin1995anditiscurrentlythemostpopularterm usedforthedisorder.Itshouldbeunderstoodasaconsensus termusedbyresearcherstodescribetheclinicalcondition of hearingloss characterized byabsent ABRswith normal OAEsandCM.1
The patients who meet the criteria for the definition ofauditoryneuropathyrepresentaheterogeneous popula-tionasinourstudy.Infact,itisquitepossiblethatnotall patientswiththeclinicalcriteriaforthisdiseasehave the samepathologicmechanismfortheirhearingdisorder.Itis likelythat therearevarious reasons thataccount for the clinical findings of auditory neuropathy.3,5,9,12---16 Also, the
patientswhowerepresentedinourstudyhadvarious etio-logicorpredisposingfactorsforANSD.Theprevalencewas
hyperbilirubinemia,detected in15%ofthepatientsinour studyandin10%to50%ofthereportedseries.17---19
Consan-guinityisverycommoninsomepopulationsinTurkey.Itis associatedwithavarietyofcongenitaldisorders,including hearinglossandANSDasinourstudy.20Inpreviousstudies,
geneticfactorshave beensuspectedtobeinvolved inthe pathogenesisofAN.Bonfilsetal.reportedrelativeswitha dominantinheritancepatternofaprogressivehearingloss withcharacteristics similar tothose of ANSD.21 Leonardis
et al. found a large Gypsy family with hereditary motor and sensory neuropathy associated with ANSD.22 Madden
etal.hypothesizedarecessiveinheritancepatternbasedon thestudyofthreefamilieswithtwoaffectedchildrenand twoother children withfamilyhistoriespositivefor hear-ingloss.23Therefore,inourstudy,wethoughtthatthetwo
brotherswithANSDcouldbesufferingfromagenetic fac-torconcerningtheirANSD.Multiple possibleetiologies for ANSDhavebeenproposed.Anestimatedhalfofallcasesare idiopathic.10Inourstudy,theetiologyof54%ofthepatients
withANSDwasnotknown.
The audiological evaluation of patients who are suspectedof havingauditoryneuropathymustbe compre-hensive.Itshouldincludethefollowingcriteria:
1. Hearingloss,usuallybilateral,ofanydegree 2. PresenceofOAEsand/orCM
3. AbnormalorabsentABR 4. Poorspeechperception 5. Absentacousticreflexes23
The diagnostic hallmarkof ANSDis the combination of othernormal hair cellactivity andabnormalafferentand efferentauditoryneuralfunctions probablyatthelevelof theeighthcranialnerveandbrainstem.Outerhaircell acti-vationisassessedindirectlybytheacousticenergyemitted bytheinnerear(OAEs)andtheelectricalresponsefromthe cochlea(CM).10 The researchersreported that80% of the
patientshadOAEs,butthattheydisappearedover timein 11%oftheirpatients.OAEswerenotrecordedintheother 9%.24 Ravehreportedthatinthreeoftheirpatients, OAEs
wereabsentandCMwaspresent.10 Inourstudy,wefound
that in 34 of our patients OAEswere absent and CM was present bilaterally, and in six of our patients OAEs were absentandCMwaspresentunilaterally.
IncochlearhearinglossOAEsandCMareabsentand, sub-sequently,theABRthresholdiselevated.However,inANSD, theABRsareabnormalorabsent,whereastheOAEsand/or CMarenormal.CasesofabsentABRsinthepresenceofmild tomoderatehearinglosswerereportedinsomeseries.3,10
TheABRsinANSDwhichareworseareacceptedincochlear SNHL,most probablybecausethesynchronyis insufficient toevokeauditorybrainstemneuralactivity.24
ItwasreportedthatthemajorityofpatientswithANSD haveabsent acousticreflex,withabout20% havinghighly atypically(elevated)acoustic reflexboth ipsilaterallyand contralaterally,buthaverecordableacousticreflexto tac-tilestimulation.24 Inourstudy,thepatientswithANSDhad
noacousticreflexes.
ThehearinglossinANSDmayrangefrommildtoprofound andaudiograms vary widely; nopredominant pattern has beendetected.25,26 The degree ofhearing lossin patients
toprofound;mostlosseswerebilateralandsymmetricalin configuration(82%),withfewpatientshavingnormalhearing inbothearsandaunilateraldisorder.24 Inourstudy,most
of the patients (12% severe---48%profound) hadsevere to profoundhearingloss.Two(5%)ofthepatientswithANSD hadnormalhearinglevel.
Given suchan incipient understanding of ANSD, ampli-fication and auditory rehabilitation for these patients is challenging.Forpediatric patients acomprehensive, mul-tidisciplinary approach to the management of ANSD is recommended.A trial of hearingaid amplificationshould beperformed depending on theaudiological information. FM system can also be tried. FM systems are recom-mended in both ANSD patients with normal hearing and hearing aid and cochlear implant users because of the improvedspeechunderstandinginnoisyconditions. There-fore, it is believed to increase success in education. In addition, at the time the cochlear implant team should evaluatethepatientandthendeterminethecandidacyfor cochlear implantation based onthe audiological findings, hearing aid benefit, status of speech language develop-mentand overall developmentskills.27 Inourstudy,in 15
ofthepatients withANSD whohad profoundhearingloss, cochlearimplantswerefitted;23ofthepatientswithANSD have been observed through their hearing aids and the remainingtwowhohadnormalhearinglevelswereapplied the FM system, but their parents did not want them to useit.
Auditoryrehabilitation withhearingaidsis difficult for patientswithANSDbecauseofthepoorwordrecognition.15
Nevertheless,hearing aidswithor without the FMsystem shouldbefirststageofmanagement.Insomecasesinwhich thepure tone hearing lossis toosmall or thereis a nor-malhearinglevelforamplificationsuchasourpatientwho hadnormalhearinglevel,theFMsystemcanbeperformed oralowgainhearingaid canbeusedtoincreaseauditory synchronization.InRaveh’sseries,onlyonein 19patients hadusefulamplificationandspeechdevelopment.10 Rance
and et al. demonstrated that nearly 50% of children affectedwithANSDbenefittedfromamplification.26 Inour
study,thesignificant improvementwasobserved between before the use of hearing aids and after the use of hearingaids.
Cochlear implant provides supraphysiologic electrical stimulation to the auditory nerve and may improve the synchronicity of the neural activity.10 Studies have
reportedimprovedaudiologicalperformance;goodimplants evoked brainstem responses, as well as good NRT after implantation.10,15,23,28 Fifteen of our patients who failed
hearingaidmanagementwerefittedwithcochlearimplants. IntraoperativeandpostoperativeNRTswerewithinnormal limits.Allpatientswithsufficientfollow-uptodate demon-stratedsignificantimprovement.However,weobservedthat statisticallytherewasnotadifferencebetweentheuseof hearingaidsandthe useof cochlear implantationgroups. Thereasonwasthatallofthecochlearimplantationusers withANSDhadseveretoprofoundhearinglossastheother CIuserswithSNHL.Itwassimilartothehearingaidusers, becausemost ofthemhad mildor moderatehearingloss. Thus, we could not find auditory perception or language developmentdifferenceinoutcomesbetweenchildrenwith ANSDandchildrenwithSNHLwhouseHAorCI.
Conclusion
Comprehensiveaudiologicalevaluationisrequiredfor accu-ratediagnosis.ThebestmanagementofANSDisprovidedby amultidisciplinaryapproach,andamplificationpreferences shouldbechosendependingonthehearinglossdegreeand languagedevelopmentasSNHL.
Authorship
C¸a˘gılGökdo˘gan wasin charge of data collection, analysis andthewritingofthepaper;S¸enayAltınyaywasinchargeof datacollection,analysisandthewritingofthepaper;Bülent Gündüzwasin chargeof datacollection, analysisandthe writingofthepaper;YusufKemalKemalo˘gluwasincharge of the writing of the paper; Yıldırım Bayazıt was in charge of the writing of the paper,and Kemal Uygurwas inchargeofthewritingofthepaper.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
References
1.SiningerYS,HoodJ,StarrA,BerlinCI,PictonTW.Hearingloss duetoauditoryneuropathy.AudiolToday.1995;7:10---3.
2.StarrA,PictonTW,SiningerY,HoodLJ,BerlinCI.Auditory neu-ropathy.Brain.1996;119:741---53.
3.StarrA,SiningerYS,PrattH.Thevarietiesofauditory neurop-athy.JBasicClinPhysiolPharmacol.2000;11:215---30.
4.FoerstA,BeutnerD,Lang-RothR,HuttenbrinkKB,vonWedelH, WalgerM.Prevalenceofauditoryneuropathy/synaptopathyina populationofchildrenwithprofoundhearingloss.IntJPediatr Otorhinolaryngol.2006;70:1415---22.
5.KrausN,OzdamarO,SteinL,ReedN.Absentauditorybrainstem response: peripheral hearingloss or brainstem dysfunction. Laryngoscope.1984;94:400---6.
6.KrausN.Auditory neuropathy:anhistoricaland current per-spective.In:SiningerY,StarrA,editors.Auditoryneuropathy:a newperspectiveonhearingdisorders.USA:SingularPub;2001. p.1---14.
7.DoyleKJ,SiningerY,StarrA.Auditoryneuropathyinchildhood. Laryngoscope.1998;208:1374---7.
8.SimmonsJL,BeauchaineKL.Auditoryneuropathy:casestudy with hyperbilirubinemia. J Basic Clin Physiol Pharmacol. 2000;11:215---30.
9.Shallop JK, Peterson A, Facer GW, Fabry LB, Driscoll CLW. Cochlearimplantsinfivecasesofauditoryneuropathy: postop-erativefindingsandprogress.Laryngoscope.2001;111:555---62.
10.Raveh E, Buller N, Badrana O, Attias J. Auditory Neurop-athy:clinicalcharacteristicsandtherapeutic approach.AmJ Otolaryngol.2007;28:302---8.
11.MasonJC, De Michele A, Stevens C,Ruth RA, Hashisaki GT. Cochlearimplantationinpatientswithauditoryneuropathyof variedetiologies.Laryngoscope.2003;113:45---9.
12.Butinar D, Zidar J, Leonardis L, Popovic M, Kalaydjieva L, AngelichevaD,etal.Hereditaryauditory,vestibular,motorand sensoryneuropathyinaSlovenianRoma(Gypsy)kindred.Ann Neurol.1999;46:36---44.
14.HamielOP,RaasAR,UpadhyayaM,FrydmanM,SarovaIP,Brand N,etal.Hereditarymotorsensoryneuropathy(Charcot-Marie ToothDisease)withnervedeafness.JPediatr.1993;123:431---4.
15.MiyamotoRT,KirkKI,RenshawJ,HussainD.Cochlear implan-tationinauditoryneuropathy.Laryngoscope.1999;109:181---5.
16.StarrA,MichalewskiHJ, ZengFG,Fujikawa SB,LinthicumF, KimCS,etal.Pathologyandphysiologyofauditoryneuropathy withanovelmutationintheMPZgene(Tyr145→SER).Brain. 2003;126:1---15.
17.ShapiroSM.Bilirubintoxicityinthedevelopingnervoussystem. PediatrNeurol.2003;29:410---21.
18.YilmazY,DegrimenciS,AkdasF,Külekc¸iS,CiprutA,YukselS, etal.Prognosticvalueofauditorybrainstemresponsefor neu-rologicoutcomeinpatientswithneonatalhyperbilirubinemia. JChildNeurol.2001;16:772---5.
19.ShapiroSM,NakamuraH.Bilirubinandtheauditorysystem.J Perinatol.2001;21:52---5.
20.JaberL, RomanoO,HalpernGJ, LivneI,GreenM,ShohatT. Awarenessaboutproblemsassociatedwithconsanguineous mar-riages:surveyamongIsraeliArabadolescents.JAdolescHealth. 2005;36:530.
21.BonfilsP,Avan P,Londero A, Narcy P,Trotoux J. Progressive hereditarydeafnesswithpredominantinnerhaircellloss.Am JOtol.1991;12:203---6.
22.LeonardisL,ZidarJ,PopovicM,TimmermanV,LöfgrenA,Van BroeckhovenC,etal.Hereditarymotorandsensoryneuropathy associatedwithauditoryneuropathyinaGypsyfamily.Pflugers Arch.2000;43:9208---10.
23.Madden C, Rutter M, Hilbert L, Greinwald JH Jr, Choo DI. Clinicalandaudiologicalfeaturesinauditoryneuropathy.Arch OtolaryngolHeadNeckSurg.2002;128:1026---30.
24.Rapin I, Gravel J. ‘‘Auditory neuropathy’’: physiologic and pathologicevidencecallsformorediagnosticspecificity.IntJ PediatrOtorhinolaryngol.2003;67:707---28.
25.Corley VM,CrabbeLS. Auditoryneuropathyand a mitochon-drial disorder in a child: case study. J Am Acad Audiol. 1999;10:484---8.
26.RanceG,BriggsRJ.Assessmentofhearingininfantswith mod-eratetoprofoundimpairment:theMelbourneexperiencewith auditorysteady-stateevokedpotentialtesting.AnnOtolRhinol LaryngolSuppl.2002;189:22---8.
27.BudenzCL,TelianSA, ArnedtC,StarrK,Arts HA,El-Kashlan HK,etal.Outcomesofcochlearimplantationinchildrenwith isolatedauditoryneuropathyversuscochlearhearingloss.Otol Neurotol.2013;34:477---83.
