auditory neuropathy / dyssynchrony ( an / ad ) is a hearing disorder characterized by an absent or atypical auditory brainstem response ( abr ) , with preservation of the cochlear microphonics ( cm ) and/or otoacoustic emissions ( oaes).1 
 2 in 1996 , starr et al first described this rare entity , drawing on their observations in 10 patients.3 the authors suggested that these patients were probably similar to those previously reported cases with a paradoxical absence of abrs and only a slight impairment of pure tone thresholds but in whom cms or oaes had not been recorded.3 
 4 
 5 also in 1998 , doyle et al reported eight patients with normal transient evoked oaes ( teoaes ) and distortion product oaes ( dpoaes ) combined with the absence or marked abnormalities of abrs.6 starr et al suggested that this type of hearing impairment is due to a disorder that impairs auditory nerve function and may have as one of its causes a neuropathy of the auditory nerve , occurring either in isolation or as part of a systemic neuropathic process.3 clinically , the diagnostic criteria of an / ad is defined as ( 1 ) sensorineural hearing loss , usually bilateral , of any degree ; ( 2 ) normal outer hair cell function as evidenced by the presence of oaes and/or cm ; ( 3 ) absent or atypical abr ; ( 4 ) understanding of speech worse than would be predicted from the behavioral or pure tone audiometry ; ( 5 ) absent acoustic reflexes to the ipsilateral and contralateral tones a 110-db hearing level.1 
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  in this retrospective study , we investigated the audiological findings , history , and clinical manifestations of patients diagnosed with an / ad at our clinic . fifteen patients with an / ad were included in this study , and their records were retrospectively investigated . all of the patients ' medical and otologic histories were recorded . otoscopic examinations were done by an otolaryngologist before testing to rule out any external or middle ear pathology that could affect audiometric measurements . then pure tone audiometry ( 250 to 8,000 hz ) , tympanometry , and acoustic reflex measurement ( 500 to 4,000 hz ) were done in a standard fashion ( interacoustic ac 40 and az 26 , denmark , assens ) . dpoaes were measured at click levels of 65 ( l1 ) and 55  db ( l2 ) peak sound pressure for the f1 and f2 components ( homoth medizinelektronik gmbh&co , kg , germany , hamburg ) . dpoae - grams were recorded in one - quarter - octave steps over a frequency range of f2 from 0.5 to 6 khz . dpoae values were plotted on a dpoaegram , which shows the emission level as a function of the f2 frequency . electrodes were placed on the forehead as a ground electrode and on both mastoids as active electrodes . alternate polarity clicks of 100-millisecond duration were presented monaurally with a repetition rate of 16.4/s . , we did not include genetic research ; we investigated only according to the history of patients . eleven male and four female patients diagnosed with an / ad ( age range : 2 to 52 years and median age : 19.3 years ) were included in this study . these patients had a history of exchange transfusion because of bilirubin levels over 20 mg / dl . three patients had family history of hearing loss , two patients had consanguineous marriage , two patients had head trauma , one patient had mental motor retardation ( psychomotor retardation ) , one patient had cerebrovascular disease , and there was no apparent causes in three patients . none of the patients with an / ad had middle or inner ear anomalies on computed tomography or magnetic resonance imaging . table 1 summarizes the patients ' demographic , clinical , and audiological features ( see also fig . 1 for a left and right ear abr and dpoae recording of a case of an / ad ) . left and right ear auditory brain stem response and distortion product otoacoustic emission recording of a case of auditory neuropathy / dyssynchrony . abbreviations : dbspl , decibels sound pressure level ; dp , distortion product ; f1 and f2 used as formulation markers . abbreviations : abr , auditory brain stem response ; an / ad , auditory neuropathy / dyssynchrony ; dpoae , distortion product otoacoustic emission . eight of 15 patients ' pure tone audiometric results showed profound hearing losses ; however , seven of them had mild to moderate hearing loss . an / ad is characterized by a unique pattern of hearing loss and distorted abr with preservation of outer hair cell function.10 
 11 an / ad comprises a spectrum of pathology affecting the auditory pathways anywhere from the inner hair cells to the brainstem . increased clinical suspicion supported by appropriate diagnostic tests is needed to establish an accurate diagnosis.12 
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  the clinical findings for auditory neuropathy are associated with several diagnoses including hyperbilirubinemia , neurodegenerative diseases , charcot - marie - tooth syndrome , and other sensorimotor neuropathologies , mitochondrial disorders , and ischemic - hypoxic neuropathy resulting from asphyxia.14 also , experimental animal models for auditory neuropathy have been proposed using the carboplatin ototoxicity and ischemic - hypoxic neuropathy methodologies.12 
 15 
 16 in our series , three patients with an / ad had neonatal hyperbilirubinemia , three patients had family history of hearing loss , two patients had consanguineous marriage , two patients had head trauma , one patient had mental motor retardation , and one patient had cerebrovascular disease . recently two mechanisms have been proposed for explaining the abnormalities of auditory function : ( 1 ) impaired synchrony among nerve fibers and/or ( 2 ) reduced neural input.17 
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 19 it is generally thought that absent or severely distorted abr is highly likely to be related to impairment of neural synchrony in the auditory pathways . similar to the previous reports , we could not obtain any response to the click stimulus . the prevalence of an / ad in patients with hearing loss ranged from 0.5 to 15% according to studies in literature.10 
 11 because there are so many possible causes for an / ad , it is difficult to estimate its exact prevalence.14 davis and hirsh suggested that 1 in every 200 hearing - impaired children had abr findings inconsistent with pure tone findings.20 permanent bilateral hearing loss is seen in 1.4 per 1,000 live births . therefore the incidence of an / ad is likely to be 1.4 per 10,000 live births . according to rance et al , an / ad would be present in 2.3 per 1,000 infants with risk factors for hearing loss . thus , if oae tests alone are used for hearing screening of infants with risk factors , 11% of infants with permanent hearing loss will be missed.14 
 21 these data are important for designing the newborn hearing screening protocols especially in developing countries . patients with an / ad complain of hearing disability , especially in the presence of noise , and tend to have word - recognition scores that are disproportionately poorer than would be expected by audiometric thresholds . in our series , all of the patients were admitted to our department with the complaint of hearing and speech disability . pure tone audiometric thresholds are variable in patients with an / ad , and the degree of hearing loss can range from mild to profound sensorineural type . eight of our patients ' pure tone audiometric results showed profound hearing losses , and seven had mild to moderate hearing loss . because oaes and cm are dependent on the integrity of cochlear outer hair cells and are  preneural  events , they may be present and normal in an / ad ; however , absent or grossly abnormal abrs are seen.14 
 22 similar findings were observed in our cases . the hallmark of an / ad is an abnormal abr reading together with a normal oae reading . however , there is a lack of actual diagnostic procedures for an / ad . other tests may also be used as part of a more comprehensive evaluation of an individual 's hearing and speech - perception abilities . electrocochleography ( ecog ) , which objectively assesses cochlear potentials , is the indicated clinical procedure to analyze cms . although transtympanic ecog yields recordings with higher amplitudes and lower test  retest variability , it has the disadvantage of being an invasive procedure . extratympanic ecog , therefore , is clinically more useful in this context , supporting an audiological diagnosis and increasing knowledge about cochlear function in an / ad . it is necessary and helpful to diagnose the sites of lesion in patients with an / ad by analyzing the patterns of cm amplitudes . therefore , recently ecog has been used for diagnosing an / ad.8 
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  some patients with an / ad lost their oae over the period of time but there was no associated change in pure tone thresholds . it has also been reported that some patients with an / ad do not have oaes but rather evidence of hair cell function was evident from cm . therefore these authors suggested that presence of cm with absent abr seems to be reliable criteria for diagnosing an / ad.24 
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  there has been controversy regarding whether to provide hearing devices ( hearing aids , personal radiofrequency [ frequency modulation ] systems , or cochlear implants ) to children with an / ad and whether to offer aural - oral or visual - manual modes of habilitation.14 
 26 berlin et al suggested that conventional amplification has little beneficial effect on an / ad patients.27 on the contrary , cone - wesson et al concluded that nearly 50% of children demonstrate some benefit from the use of conventional hearing aids and that a trial of amplification is warranted.14 
 21 cochlear implantation may also be an option for hearing rehabilitation . although the outcome of cochlear implantation in children with an / ad might vary , it is favorable in most cases . cochlear implantation seems a justified hearing rehabilitation option for children with an / ad and limited benefits from conventional hearing aids.28 
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 30 in our series , we obtained some development in hearing and speech abilities using a conventional hearing aid in one case . the current position statement of the joint committee on infant hearing ( 2007 ) calls for ( 1 ) physiological hearing screening of all infants before they are 1  month old , ( 2 ) confirmation of the hearing loss before 3 months of age , and ( 3 ) commencement of an interdisciplinary intervention program before the infant is 6 months old . moreover , the scope of disorders targeted for identification has been expanded to include neural hearing loss ( especially an / ad ) in addition to sensorineural and permanent conductive hearing loss.31 although an / ad affects only a small portion of all persons with hearing loss , the infant , child , or adult with an / ad is often most disabled by the hearing disorder because of the lack of knowledge about its cause and , more importantly , its treatment . continued research regarding the causes and pathologies underlying this disorder is needed.10 however , it is also necessary to develop methods to reduce false - negative screening results and to provide accurate diagnosis for the disorder.2 a combined oae and abr screening procedure may be considered to overcome the limitations of oae - only procedures especially in high - risk infants . also , it should be kept in mind that adult an / d cases may be related with systemic neurological diseases .
introduction  auditory neuropathy / dyssynchrony ( an / ad ) comprises a spectrum of pathology affecting the auditory pathways anywhere from the inner hair cells to the brainstem . 
 it is characterized by an absent or atypical auditory brainstem response ( abr ) with preservation of the cochlear microphonics and/or otoacoustic emissions ( oaes ) . 
 objective  retrospective analysis of patients with an / ad . 
 methods  fifteen patients with an / ad were included in this study and their records were retrospectively investigated . 
 results  possible etiology of an / ad was neonatal hyperbilirubinemia in three patients , family history of hearing loss in three patients , consanguineous marriage in two patients , head trauma in two patients , mental motor retardation in one patient , cerebrovascular disease in one patient , and there was no apparent cause in three patients . 
 conclusion  otolaryngologists should keep in mind the diagnosis of an / ad especially in patients complaining of difficulty in hearing and speech and audiological evidence of disassociation between pure tone and speech audiometry . 
 abr and oae testing is recommended in these patients for an / ad diagnosis .