Audiological Features of Auditory Neuropathy Spectrum Disorders
Main Article Content
Abstract
Objective: Auditory neuropathy spectrum disorder (ANSD) is hearing dysfunction with a broad spectrum of audiological clinical features and rehabilitation outcomes.
Electrocochleography and electrically evoked auditory brainstem responses (eABR) are useful tool to predict site of lesion and type of ANSD (synaptopathy or neuropathy), especially in cases with unknown etiology of ANSD. Therefore, the aim of this study was to evaluate the applicability of intracochlear electrocochleography and eABR registration after cochlear implantation for revealing electrophysiological features of different forms of ANSD and predicting rehabilitation outcomes.
Material and methods: 22 children with ANSD of different etiology were enrolled in the study. Intracochlear electrocochleography and eABR registration after cochlear implantation were performed in 23 ears. Seven children had OTOF-related ANSD, 2 children - cochlear nerve deficiency, in 8 cases ANSD probably was due to prematurity, in 1 – due to hyperbilirubinemia, 4 cases were with unknown etiology of ANSD.
Results: Cochlear microphonic was recordable in 21 cases. The summating and compound action potentials were recordable in 7 cochlear implant users. There was diversity in electrocochleography results within the group of children with the same etiology of ANSD. On the other hand, there were cases when electrocochleography results were almost identical even in patients with different etiology and pathophysiology of ANSD.
The eABR were registered in 7 children with OTOF-related ANSD and in 9 children with perinatal risk factors. Presence of eABRs in OTOF-related cases matches the pathophysiology of auditory synaptopathy. In 3 ears with hypoplastic cochlear nerve eABRs were absent or partially recordable only in bipolar mode of stimulation of basal turn. In children with unknown etiology in 2 cases eABRs were recordable from all stimulated electrodes (auditory synaptopathy) and in other 2 cases were absent (auditory neuropathy). Rehabilitation outcomes after cochlear implantation corresponded to the results of eABR registration and were better among children with eABRs.
Conclusions: Intracochlear electrocochleography does not provide a reliable differentiation of different types of ANSD. Registration of eABRs in monopolar stimulation mode from intracochlear electrodes is valuable for differentiating ANSD types and predicting outcomes of cochlear implantation in children with ANSD.
Keywords:
Auditory Neuropathy Spectrum Disorder, Electrocochleography, Electrically Evoked Compound Action Potential, Electrically Evoked Brainstem Responses, Cochlear Microphonic, Otoacoustic Emission, Cochlear Implantation
Article Details
How to Cite
TAVARTKILADZE,, George A.; LALAYANTS, Maria R..
Audiological Features of Auditory Neuropathy Spectrum Disorders.
Medical Research Archives, [S.l.], v. 13, n. 11, nov. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7079>. Date accessed: 05 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i11.7079.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Santarelli S, Starr A, Michalewski HJ., Arslan E. Neu-ral and receptor cochlear potentials obtained by transtympanic electrocochleography in auditory neu-ropathy. Clin Neurophysiol. 2008;119(5):1028-1041. doi:10.1016/j.clinph.2008.01.018.
2. Rance G, Starr A. Pathophysiological mechanisms and functional hearing consequences of auditory neuropathy Brain. 2015 Nov;138(Pt 11):3141-3158. doi:10.1093/brain/awv270. Epub 2015 Oct 12.
3. Kaga K, Starr A. Neuropathies of the auditory and vestibular eighth cranial nerves. Tokyo: Springer; 2009. doi:10.1007/978-4-431-09433-3. ISBN: 978-4-431-09432-6.
4. Starr A, Sininger Y, Nguyen T, Michalewski HJ, Oba S, Abdala C. Cochlear receptor (microphonic and summating potentials, otoacoustic emissions) and au-ditory pathway (auditory brain stem potentials) ac-tivity in auditory neuropathy. Ear Hear. 2001 Apr;22(2):91-99. doi: 10.1097/00003446-200104000-00002.
5. Kaga K, Nakamura M, Shinogami M, Tsuzuku T, Yamada K, Shindo M. Auditory nerve disease of both ears revealed by auditory brainstem responses, electrocochleography and otoacoustic emissions. Scand Audiol. 1996;25(4):233–238. doi: 10.3109/01050399609074960.
6. Rance G. Auditory neuropathy/dys-synchrony and its perceptual consequences. Trends Amplif. 2005;9(1):1-43. doi: 10.1177/108471380500900102.
7. Berlin CI, Morlet T, Hood LJ. Auditory neuropa-thy/dyssynchrony: its diagnosis and management. Pediatr Clin North Am. 2003 Apr;50(2):331-340, vii-viii. doi: 10.1016/s0031-3955(03)00031-32.
8. Berlin CI, Hood LJ, Morlet T, et al. Multi-site diagnosis and management of 260 patients with auditory neu-ropathy/dys-synchrony (auditory neuropathy spec-trum disorder). Int J Audiol. 2010 Jan;49(1):30-43. doi: 10.3109/14992020903160892.
9. Zeng FG, Kong YY, Michalewski HJ, Starr A. Percep-tual consequences of disrupted auditory nerve activi-ty. J Neurophysiol. 2005 Jun; 93(6):3050–3063. doi:10.1152/jn.00985.2004. Epub 2004 Dec 22.
10. Starr A, Picton TW, Sininger Y, Hood L J, Berlin C I. Auditory neuropathy. Brain.1996 Jun;119(Pt 3), 741–753. doi: 10.1093/brain/119.3.741.
11. Doyle K J, Sininger Y, Starr A. Auditory neuropathy in childhood. Laryngoscope. 1998 Sep;108(9):1374–1377. doi: 10.1097/00005537-199809000-00022.
12. Zeng FG, Oba S, Garde S, Sininge Y, Starr A. Tem-poral and speech processing deficits in auditory neu-ropathy. Neurorep. 1999 Nov 8; 10(16):3429–3435. doi: 10.1097/00001756-199911080-00031.
13. Fuchs PA, Glowatzki E, Moser T. The afferent syn-apse of cochlear hair cells. Curr Opin Neurobiol. 2003 Aug;13(4):452–458. doi: 10.1016/S0959-4388(03) 00098-9.
14. Rapin I, Gravel J. “Auditory neuropathy”: physiologic and pathologic evidence calls for more diagnostic specificity. Int J Pediatr Otorhinolaryngol. 2003 Jul;67(7):707–728. doi: 10.1016/S0165-5876(03) 00103-4.
15. Santarelli R, Rossi R, Scimemi P, et al. OPA1-related auditory neuropathy: site of lesion and outcome of cochlear implantation. Brain. 2015 Mar; 138(Pt3):563–576 doi:10.1093/brain/awu378.
16. Kitao K, Mutai H, Namba K, et al. Deterioration in distortion product otoacoustic emissions in auditory neuropathy patients with distinct clinical and genetic backgrounds. Ear Hear. 2019 Jan/Feb;40(1):184-191. doi: 10.1097/AUD.0000000000000586.
17. Moser T, Starr A. Auditory neuropathy-neural and synaptic mechanisms. Nat Rev Neurol. 2016 Mar;12(3):135–149. doi: 10.1038/nrneurol.2016.10. Epub 2016 Feb 19.
18. Shearer AE, Hansen MR. Auditory synaptopathy, au-ditory neuropathy, and cochlear implantation. Laryn-goscope Investig Otolaryngol. 2019 Jul 1; 4(4): 429–440. doi: 10.1002/lio2.288.
19. Ehrmann-Müller D, Cebulla M, Rak K, et al. Evalua-tion and therapy outcome in children with auditory neuropathy spectrum disorder (ANSD). Int J Pediatr Otorhinolaryngol. 2019 Dec;127: 109618. doi: 10.1016/j.ijporl.2019.109681.
20. Mittal R, Ramesh AV, Panwar SS, Nilkanthan A, Nair S, Mehra PR. Auditory neuropathy spectrum disorder: its prevalence and audiological characteristics in an Indian tertiary care hospital. Int J Pediatr Otorhino-laryngol. 2012 Sep;76(9):1351-1354. doi: 10.1016/j.ijporl.2012.06.005. Epub 2012 Jul 12.
21. Shi W, Ji F, Lan L, et al. Characteristics of cochlear microphonics in infants and young children with auditory neuropathy. Acta Otolaryngol. 2012 Feb; 132(2):188–196. https://doi.org/10.3109/00016489.2011.630016. Epub 2011 Nov 21.
22. De Siati RD, Rosenzweig F, Gersdorff G, Gregoire A, Rombaux P, Deggouj N. Auditory neuropathy spec-trum disorders: from diagnosis to treatment: Litera-ture review and case reports. J Clin Med. 2020 Apr 15;9(4):1074. doi: 10.3390/jcm9041074.
23. Amatuzzi M, Liberman C, Northrop C. Selective inner hair cell loss in prematurity: A temporal bone study of infants from a neonatal intensive care unit. J Assoc Res Otolaryngol. 2011 Oct; 12(5): 595-604. DOI: 10.1007/s10162-011-0273-4.
24. Mathew S, Jain C. A systematic review on the imag-ing findings in auditory neuropathy spectrum disor-der. J Otol. 2024 Jul;19(3):166-172. doi: 10.1016/j.joto.2024.09.001. Epub 2024 Oct 20. PMID: 39735244; PMCID: PMC11681793.
25. Soares IA, Menezes PL, Carnaúba AT, Andrade KC, Lins OG. Estudo do microfonismo coclear na neuropa-tia auditiva. Braz J Otorhinolaryngol. 2016, 82(6):722–736. https://doi.org/10.1016/j.bjorl.2015.11.022.
26. Santarelli R. Information from cochlear potentials and genetic mutations helps localize the lesion site in au-ditory neuropathy. Genome Med. 2010 Dec 22; 2(12): 91. doi: 10.1186/gm212.
27. Santarelli R, Arslan E. Electrocochleography in audi-tory neuropathy. Hear Res. 2002 Aug; 170(1-2): 32–47. doi:10.1016/s0378-5955(02)00450-1.
28. Abbas PJ, Brown CJ. Assessment of responses to coch-lear implant stimulation at different levels of the au-ditory pathway. Hear Res. 2015 Apr; 322: 67–76. doi:10.1016/j.heares.2014.10.011. Epub 2014 Nov 4.
29. Fitzpatrick DC, Campbell AP, Choudhury B, et al. Round window electrocochleography just before cochlear implantation: relationship to word recogni-tion outcomes in adults. Otol Neurotol. 2014 Jan;35(1):64-71. doi: 10.1097/MAO.0000000000000219.
30. Formeister EJ, McClellan JH, Merwin WH 3rd, et al. Intraoperative round window electrocochleography and speech perception outcomes in pediatric cochlear implant recipients. Ear Hear. 2015 Mar-Apr;36(2):249-60. doi: 10.1097/AUD.0000000000000106.
31. Adunka OF, Mlot S, Suberman TA, et al. Intracochle-ar recordings of electrophysiological parameters in-dicating cochlear damage. Otol Neurotol. 2010 Oct;31(8): 1233–1241. doi: 10.1097/MAO.0b013e3181f1ffdf.
32. Mandala M, Colletti L, Tonoli G, Colletti V. Electro-cochleography during cochlear implantation for hearing preservation. Otolaryngol Head Neck Surg. 2012 May;146(5): 774–781. doi: 10.1177/0194599811435895.
33. Radeloff A, Shehata-Dieler W, Scherzed A, et al. Intraoperative monitoring using cochlear microphonics in cochlear implant patients with residual hearing. Otol Neurotol. 2012 Apr; 33(3): 348–354. doi: 10.1097/MAO.0b013e318248ea86.
34. Calloway NH, Fitzpatrick DC, Campbell AP, et al. Intracochlear electrocochleography during cochlear implantation. Otol Neurotol. 2014 Sep;35(8): 1451–1457. doi: 10.1097/MAO.0000000000000451.
35. Campbell L, Kaicer A, Briggs R, O’Leary S. Cochlear response telemetry: intracochlear electrocochleo-graphy via cochlear implant neural response teleme-try pilot study results. Otol Neurotol. 2015 Mar; 36(3): 399–405. doi: 10.1097/MAO.0000 000000000678
36. Dalbert A, Huber A, Veraguth D, Roosli C, Pfiffner F. Assessment of cochlear trauma during cochlear im-plantation using electrocochleography and cone beam computed tomography. Otol Neurotol. 2016 Jun;37(5): 446–453. doi: 10.1097/MAO.00000000 00000998
37. Dalbert A, Sim JH, Gerig R, Pfiffner F, Roosli C, Hu-ber A. Correlation of electrophysiological properties and hearing preservation in cochlear implant pa-tients. Otol Neurotol. 2015 Aug;36(7): 1172–1180. doi: 10.1097/MAO.0000000000000768.
38. Barnes JH, Yin LX, Saoji AA, Carlson ML. Electrococh-leography in cochlear implantation: Development, applications, and future directions. World J Otorhino-laryngol Head Neck Surg. 2020 Jun 4;7(2):94-100. doi: 10.1016/j.wjorl.2020.04.006.
39. Bester CW, Campbell L, Dragovic A, Collins A, O’Leary SJ. Characterizing electrocochleography in cochlear implant recipients with residual low-frequency hearing. Front Neurosci. 2017 Mar; 11:141. doi: 10.3389/fnins.2017.00141.
40. Liberman MC, Epstein MJ, Cleveland SS, Wang H, Maison SF. Toward a differential diagnosis of hidden hearing loss in humans. PLoS ONE. 2016 Sep; 11(9):e0162726.
doi: 10.1371/journal.pone.0162726.
41. Fontenot TE, Giardina CK, Fitzpatrick DC. A model-based approach for separating the cochlear micro-phonic from the auditory nerve neurophonic in the ongoing response using electrocochleography. Front Neurosci. 2017 Oct 23;11:592. doi: 10.3389/fnins.2017.00592.
42. Durrant JD, Wang J, Ding DL, Salvi RJ. Are inner or outer hair cells the source of summating potentials recorded from the round window? J Acoust Soc Am. 1998 Jul; 104(1): 370–377. doi: 10.1121/1.423293.
43. Pappa AK, Hutson KA, Scott WC, et al. Hair cell and neural contributions to the cochlear summating poten-tial. J Neurophysiol. 2019 Jun 1; 121(6): 2163–2180. doi: 10.1152/jn.00006.2019. Epub 2019 Apr 3.
44. Snyder RL, Schreiner CE. The auditory neurophonic: Basic properties. Hear Res. 1984 Sep; 15(3): 261–280. doi:10.1016/0378-5955(84)90033-9.
45. Henry KR. Auditory nerve neurophonic recorded from the round window of the Mongolian Gerbil. Hear Res. 1995 Oct, 90(1-2): 176–184. doi:10.1016/0378-5955(95)00162-6.
46. Lichtenhan JT, Cooper NP, Guinan JJ Jr. A new audi-tory threshold estimation technique for low frequen-cies: proof of concept. Ear Hear. 2013 Jan-Feb;34(1), 42–51. doi: 10.1097/AUD.0b013e31825f9bd3.
47. Forgues M, Koehn HA, Dunnon AK, et al. Distinguish-ing hair cell from neural potentials recorded at the round window. J Neurophysiol. 2014 Feb;111(3):580-593.
doi: 10.1152/jn.00446.2013. Epub 2013 Oct 16.
48. Bester C, O'Leary SJ, Venail F., et al. Improving real-time feedback during cochlear implantation: The au-ditory nerve neurophonic/cochlear microphonic ratio. Ear Hear. 2025 May-Jun; 46(3):687-695. doi:10.1097/AUD.0000000000001613. Epub 2025 Jan 10.
49. Santarelli R, del Castillo I, Cama E, Scimemi P, Starr A. Audibility, speech perception and processing of temporal cues in ribbon synaptic disorders due to OTOF mutations. Hear Res. 2015 Dec;330(Pt B):200-212. doi: 10.1016/j.heares.2015.07.007. Epub 2015 Jul 15.
50. Khimich D, Nouvtan R, Pujol R, et al. Hair cell synap-tic ribbons are essential for synchronous auditory sig-naling. Nature. 2005 Apr 14;434(7036), 889–894. doi: 10.1038/nature03418. PMID: 15829963.
51. Buran BN, Strenzke N, Neef A, Gundelfinger ED, Moser T, Liberman MC. Onset coding is degraded in auditory nerve fibers from mutant mice lacking syn-aptic ribbons. J Neurosci. 2010 Jun 2;30(22):7587-7597. doi: 10.1523/jneurosci.0389- 10.2010.
52. Wichmann C, Moser T. Relating structure and function of inner hair cell ribbon synapses. Cell Tissue Res. 2015 Jul;361(1):95-114. doi: 10.1007/s00441-014-2102-7. Epub 2015 Jan 22.
53. Riggs WJ, Roche JP, Giardina CK, et al. Intraopera-tive electrocochleographic characteristics of auditory neuropathy spectrum disorder in cochlear implant subjects. Front Neurosci. 2017 Jul 19;11:416. doi: 10.3389/fnins.2017.00416.
54. Teagle HF, Roush PA, Woodard JS, et al. Cochlear implantation in children with auditory neuropathy spectrum disorder. Ear Hear. 2010 Jun;31(3):325-335.
doi: 10.1097/AUD.0b013e3181ce693b.
55. Roush P, Frymark T, Venediktov R, Wang B. Audio-logic management of auditory neuropathy spectrum disorder in children: A systematic review of the liter-ature. Am J Audiol. 2011 Dec; 20(2):159-170. doi:10.1044/1059-0889(2011/10-0032.
56. Rance G, Barker EJ. Speech perception in children with auditory neuropathy/dyssynchrony managed with either hearing AIDS or cochlear implants. Otol Neurotol. 2008 Feb;29(2):179-182. doi: 10.1097/mao.0b013e31815e92fd.
57. Buchman CA, Roush PA, Teagle HF, Brown CJ, Zdan-ski CJ, Grose JH. Auditory neuropathy characteristics in children with cochlear nerve deficiency. Ear Hear. 2006 Aug;27(4):399-408. doi: 10.1097/01.aud. 0000224100.30525.ab.
58. Stuermer KJ, Beutner D, Foerst A, Hahn M, Lang-Roth R, Walger M. Electrocochleography in children with auditory synaptopathy/neuropathy: Diagnostic find-ings and characteristic parameters. Int J Pediatri Oto-rhinolaryngol. 2015 Feb; 79(2):139-145. doi:10.1016/j.ijporl.2014.11.025.
59. Budenz CL, Starr K, Arnedt C, Telian SA, Arts HA, El-Kashlan HK, Zwolan TA. Speech and language out-comes of cochlear implantation in children with iso-lated auditory neuropathy versus cochlear hearing loss. Otol Neurotol. 2013 Dec;34(9):1615-1621. doi: 10.1097/MAO.0b013e3182a1ab5b.
60. Breneman AI, Gifford RH, Dejong MD. Cochlear im-plantation in children with auditory neuropathy spec-trum disorder: Long-term outcomes. J Am Acad Audiol. 2012 Jan 1;23(1):5-17. doi:10.3766/jaaa.23.1.2.
61. Rance G, Beer DE, Cone-Wesson B, et al. Clinical findings for a group of infants and young children with auditory neuropathy. Ear Hear. 1999 Jun;20(3):238-252. doi: 10.1097/00003446-199906000-00006.
62. Santarelli R. Information from cochlear potentials and genetic mutations helps localize the lesion site in au-ditory neuropathy. Genome Med. 2010; 91:2-10. Doi:10.1186/gm212.
63. Rodriguez-Ballesteros M, Reynoso, Olarte M, et al. A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy. Hum Mutat. 2008 May 22; 29(6):823-831. doi.org/10.1002/humu.20708
64. He S, Shahsavarani BS, McFayden TC, et al. Respon-siveness of the electrically stimulated cochlear nerve in children with cochlear nerve deficiency. Ear Hear. 2018 Mar/Apr;39(2):238-250. doi: 10.1097/AUD.0000000000000467. PMID: 28678078; PMCID: PMC5748379.
65. Huang T, Santarelli R, Starr A. Mutation of OPA1 gene causes deafness by affecting function of audi-tory nerve terminals. Brain Res. 2009 Dec;1300: 97-104. doi:10.1016/j.brainres.2009.08.083. Epub 2009 Sep 3.
66. Fontenot TE, Giardina CK, Teagle HF, et al. Clinical role of electrocochleography in children with audito-ry neuropathy spectrum disorder. Int J Pediatr Oto-rhinolaryngol. 2017 Aug; 99:120-127.` doi:10.1016/j.ijporl.2017.05.026.
67. Zhan KY, Adunka OF, Eshraghi A, et al. Electrophysi-ology and genetic testing in the precision medicine of congenital deafness: A review. J Otol. 2021 Jan;16(1):40-46. doi: 10.1016/j.joto.2020. 07.003. Epub 2020 Aug 1.
68. Tavartkiladze GA, Bakhshinyan VV. Objective measures at different stages of cochlear implanta-tion: A Data Analysis. Med Res Arch. 2025;13(1). doi:10.18103/mra.v13i1.6171.
69. Brown CJ, Abbas PJ, Fryauf-Bertschy H, Kelsay D, Gantz BJ. Intraoperative and postoperative electri-cally evoked auditory brain stem responses in Nucle-us cochlear implant users: Implications for the fitting process. Ear Hear. 1994 Apr;15(2):168-176. doi: 10.1097/00003446-199404000-00006.
70. Seo YJ, Kwak C, Kim S, Park YA, Park KH, Han W. Update on Bone-Con¬duction Auditory Brainstem Re-sponses: A Review. J Audiol Otol. 2018 Apr; 22(2):53-58. doi:10.7874/jao.2017.00346.
71. Tavartkiladze G.A., Potalova L.A., Kruglov A.V., Be-lov O.A. Effect of stimulation parameters on electri-cally evoked auditory brainstem responses. Acta Otolaryngol (Stockh). 2000;120(2): 214-217. doi:10.1080/000164800750000946.
72. Minami S, Kaga K. EABR of inner ear malformation and cochlear nerve deficiency after cochlear implan-tation in children. In: Kaga K, ed. Cochlear Implanta-tion in Children with Inner Ear Malformation and Cochlear Nerve Deficiency. Springer Link; 2017:97-109. doi:10.1007/978-981-10-1400-0_8.
73. Lalayants M. Auditory neuropathy spectrum disorder: Genetic and electrophysiological testing for predict-ing rehabilitation outcomes after cochlear implanta-tion. Latest advances in cochlear implant technologies and related clinical applications. IntechOpen. 2023 Oct 4. Available from: http://dx.doi.org/10.5772/intechopen.110430.
74. Gibson WP, Sanli H. Auditory neuropathy: an up-date. Ear Hear. 2007 Apr;28(2 Suppl): 102S-106S. doi: 10.1097/AUD.0b013e3180315392.
75. McMahon CM, Patuzzi RB, Gibson WP, Sanli H. Fre-quency-specific electrocochleography indicates that presynaptic and postsynaptic mechanisms of audito-ry neuropathy exist. Ear Hear. 2008 Jun;29(3):314-25. doi: 10.1097/AUD.0b013e3181 662c2a.
76. Kaga K. ABRs and electrically evoked ABRs in chil-dren. In: Modern Otology and Neurotology. Tokyo: Springer; 2022. doi: 10.1007/978-4-431-54189-9_1.
77. Dziemba OC, Hocke T, Müller A, Kaftan H. Excitation characteristic of a bipolar stimulus for broadband stimulation in measurements of electrically evoked auditory potentials. Z Med Phys. 2018 Feb;28(1):73-77. doi: 10.1016/j.zemedi.2017.09.008. Epub 2017 Oct 18. PMID: 29054678.
78. Bayri Ulukan M, Ciprut A. Intracochlear electrococh-leography findings in cochlear implant recipients with auditory neuropathy spectrum disorder. Int J Pediatr Otorinolaryngol. 2023. 170: 111596. https://doi.org/10.1016/j.ijporl.2023.111596
79. Santarelli R, Scimemi P, La Morgia C, Cama E, Del Castillo I, Carelli V. Electrocochleography in auditory neuropathy related to mutations in the OTOF or OPA1 gene. Audiol Res. 2021 Nov 26;11(4):639-652. doi: 10.3390/audiolres11040059. PMID: 34940017; PMCID: PMC8698970.
80. Jeon JH, Bae MR, Song MH, Noh SH, Choi KH, Choi JY. Relationship between electrically evoked audito-ry brainstem response and auditory performance af-ter cochlear implant in patients with auditory neu-ropathy spectrum disorder. Otol Neurotol. 2013 Sep;34(7):1261-1266. doi: 10.1097/MAO.0b013e318291c632.
2. Rance G, Starr A. Pathophysiological mechanisms and functional hearing consequences of auditory neuropathy Brain. 2015 Nov;138(Pt 11):3141-3158. doi:10.1093/brain/awv270. Epub 2015 Oct 12.
3. Kaga K, Starr A. Neuropathies of the auditory and vestibular eighth cranial nerves. Tokyo: Springer; 2009. doi:10.1007/978-4-431-09433-3. ISBN: 978-4-431-09432-6.
4. Starr A, Sininger Y, Nguyen T, Michalewski HJ, Oba S, Abdala C. Cochlear receptor (microphonic and summating potentials, otoacoustic emissions) and au-ditory pathway (auditory brain stem potentials) ac-tivity in auditory neuropathy. Ear Hear. 2001 Apr;22(2):91-99. doi: 10.1097/00003446-200104000-00002.
5. Kaga K, Nakamura M, Shinogami M, Tsuzuku T, Yamada K, Shindo M. Auditory nerve disease of both ears revealed by auditory brainstem responses, electrocochleography and otoacoustic emissions. Scand Audiol. 1996;25(4):233–238. doi: 10.3109/01050399609074960.
6. Rance G. Auditory neuropathy/dys-synchrony and its perceptual consequences. Trends Amplif. 2005;9(1):1-43. doi: 10.1177/108471380500900102.
7. Berlin CI, Morlet T, Hood LJ. Auditory neuropa-thy/dyssynchrony: its diagnosis and management. Pediatr Clin North Am. 2003 Apr;50(2):331-340, vii-viii. doi: 10.1016/s0031-3955(03)00031-32.
8. Berlin CI, Hood LJ, Morlet T, et al. Multi-site diagnosis and management of 260 patients with auditory neu-ropathy/dys-synchrony (auditory neuropathy spec-trum disorder). Int J Audiol. 2010 Jan;49(1):30-43. doi: 10.3109/14992020903160892.
9. Zeng FG, Kong YY, Michalewski HJ, Starr A. Percep-tual consequences of disrupted auditory nerve activi-ty. J Neurophysiol. 2005 Jun; 93(6):3050–3063. doi:10.1152/jn.00985.2004. Epub 2004 Dec 22.
10. Starr A, Picton TW, Sininger Y, Hood L J, Berlin C I. Auditory neuropathy. Brain.1996 Jun;119(Pt 3), 741–753. doi: 10.1093/brain/119.3.741.
11. Doyle K J, Sininger Y, Starr A. Auditory neuropathy in childhood. Laryngoscope. 1998 Sep;108(9):1374–1377. doi: 10.1097/00005537-199809000-00022.
12. Zeng FG, Oba S, Garde S, Sininge Y, Starr A. Tem-poral and speech processing deficits in auditory neu-ropathy. Neurorep. 1999 Nov 8; 10(16):3429–3435. doi: 10.1097/00001756-199911080-00031.
13. Fuchs PA, Glowatzki E, Moser T. The afferent syn-apse of cochlear hair cells. Curr Opin Neurobiol. 2003 Aug;13(4):452–458. doi: 10.1016/S0959-4388(03) 00098-9.
14. Rapin I, Gravel J. “Auditory neuropathy”: physiologic and pathologic evidence calls for more diagnostic specificity. Int J Pediatr Otorhinolaryngol. 2003 Jul;67(7):707–728. doi: 10.1016/S0165-5876(03) 00103-4.
15. Santarelli R, Rossi R, Scimemi P, et al. OPA1-related auditory neuropathy: site of lesion and outcome of cochlear implantation. Brain. 2015 Mar; 138(Pt3):563–576 doi:10.1093/brain/awu378.
16. Kitao K, Mutai H, Namba K, et al. Deterioration in distortion product otoacoustic emissions in auditory neuropathy patients with distinct clinical and genetic backgrounds. Ear Hear. 2019 Jan/Feb;40(1):184-191. doi: 10.1097/AUD.0000000000000586.
17. Moser T, Starr A. Auditory neuropathy-neural and synaptic mechanisms. Nat Rev Neurol. 2016 Mar;12(3):135–149. doi: 10.1038/nrneurol.2016.10. Epub 2016 Feb 19.
18. Shearer AE, Hansen MR. Auditory synaptopathy, au-ditory neuropathy, and cochlear implantation. Laryn-goscope Investig Otolaryngol. 2019 Jul 1; 4(4): 429–440. doi: 10.1002/lio2.288.
19. Ehrmann-Müller D, Cebulla M, Rak K, et al. Evalua-tion and therapy outcome in children with auditory neuropathy spectrum disorder (ANSD). Int J Pediatr Otorhinolaryngol. 2019 Dec;127: 109618. doi: 10.1016/j.ijporl.2019.109681.
20. Mittal R, Ramesh AV, Panwar SS, Nilkanthan A, Nair S, Mehra PR. Auditory neuropathy spectrum disorder: its prevalence and audiological characteristics in an Indian tertiary care hospital. Int J Pediatr Otorhino-laryngol. 2012 Sep;76(9):1351-1354. doi: 10.1016/j.ijporl.2012.06.005. Epub 2012 Jul 12.
21. Shi W, Ji F, Lan L, et al. Characteristics of cochlear microphonics in infants and young children with auditory neuropathy. Acta Otolaryngol. 2012 Feb; 132(2):188–196. https://doi.org/10.3109/00016489.2011.630016. Epub 2011 Nov 21.
22. De Siati RD, Rosenzweig F, Gersdorff G, Gregoire A, Rombaux P, Deggouj N. Auditory neuropathy spec-trum disorders: from diagnosis to treatment: Litera-ture review and case reports. J Clin Med. 2020 Apr 15;9(4):1074. doi: 10.3390/jcm9041074.
23. Amatuzzi M, Liberman C, Northrop C. Selective inner hair cell loss in prematurity: A temporal bone study of infants from a neonatal intensive care unit. J Assoc Res Otolaryngol. 2011 Oct; 12(5): 595-604. DOI: 10.1007/s10162-011-0273-4.
24. Mathew S, Jain C. A systematic review on the imag-ing findings in auditory neuropathy spectrum disor-der. J Otol. 2024 Jul;19(3):166-172. doi: 10.1016/j.joto.2024.09.001. Epub 2024 Oct 20. PMID: 39735244; PMCID: PMC11681793.
25. Soares IA, Menezes PL, Carnaúba AT, Andrade KC, Lins OG. Estudo do microfonismo coclear na neuropa-tia auditiva. Braz J Otorhinolaryngol. 2016, 82(6):722–736. https://doi.org/10.1016/j.bjorl.2015.11.022.
26. Santarelli R. Information from cochlear potentials and genetic mutations helps localize the lesion site in au-ditory neuropathy. Genome Med. 2010 Dec 22; 2(12): 91. doi: 10.1186/gm212.
27. Santarelli R, Arslan E. Electrocochleography in audi-tory neuropathy. Hear Res. 2002 Aug; 170(1-2): 32–47. doi:10.1016/s0378-5955(02)00450-1.
28. Abbas PJ, Brown CJ. Assessment of responses to coch-lear implant stimulation at different levels of the au-ditory pathway. Hear Res. 2015 Apr; 322: 67–76. doi:10.1016/j.heares.2014.10.011. Epub 2014 Nov 4.
29. Fitzpatrick DC, Campbell AP, Choudhury B, et al. Round window electrocochleography just before cochlear implantation: relationship to word recogni-tion outcomes in adults. Otol Neurotol. 2014 Jan;35(1):64-71. doi: 10.1097/MAO.0000000000000219.
30. Formeister EJ, McClellan JH, Merwin WH 3rd, et al. Intraoperative round window electrocochleography and speech perception outcomes in pediatric cochlear implant recipients. Ear Hear. 2015 Mar-Apr;36(2):249-60. doi: 10.1097/AUD.0000000000000106.
31. Adunka OF, Mlot S, Suberman TA, et al. Intracochle-ar recordings of electrophysiological parameters in-dicating cochlear damage. Otol Neurotol. 2010 Oct;31(8): 1233–1241. doi: 10.1097/MAO.0b013e3181f1ffdf.
32. Mandala M, Colletti L, Tonoli G, Colletti V. Electro-cochleography during cochlear implantation for hearing preservation. Otolaryngol Head Neck Surg. 2012 May;146(5): 774–781. doi: 10.1177/0194599811435895.
33. Radeloff A, Shehata-Dieler W, Scherzed A, et al. Intraoperative monitoring using cochlear microphonics in cochlear implant patients with residual hearing. Otol Neurotol. 2012 Apr; 33(3): 348–354. doi: 10.1097/MAO.0b013e318248ea86.
34. Calloway NH, Fitzpatrick DC, Campbell AP, et al. Intracochlear electrocochleography during cochlear implantation. Otol Neurotol. 2014 Sep;35(8): 1451–1457. doi: 10.1097/MAO.0000000000000451.
35. Campbell L, Kaicer A, Briggs R, O’Leary S. Cochlear response telemetry: intracochlear electrocochleo-graphy via cochlear implant neural response teleme-try pilot study results. Otol Neurotol. 2015 Mar; 36(3): 399–405. doi: 10.1097/MAO.0000 000000000678
36. Dalbert A, Huber A, Veraguth D, Roosli C, Pfiffner F. Assessment of cochlear trauma during cochlear im-plantation using electrocochleography and cone beam computed tomography. Otol Neurotol. 2016 Jun;37(5): 446–453. doi: 10.1097/MAO.00000000 00000998
37. Dalbert A, Sim JH, Gerig R, Pfiffner F, Roosli C, Hu-ber A. Correlation of electrophysiological properties and hearing preservation in cochlear implant pa-tients. Otol Neurotol. 2015 Aug;36(7): 1172–1180. doi: 10.1097/MAO.0000000000000768.
38. Barnes JH, Yin LX, Saoji AA, Carlson ML. Electrococh-leography in cochlear implantation: Development, applications, and future directions. World J Otorhino-laryngol Head Neck Surg. 2020 Jun 4;7(2):94-100. doi: 10.1016/j.wjorl.2020.04.006.
39. Bester CW, Campbell L, Dragovic A, Collins A, O’Leary SJ. Characterizing electrocochleography in cochlear implant recipients with residual low-frequency hearing. Front Neurosci. 2017 Mar; 11:141. doi: 10.3389/fnins.2017.00141.
40. Liberman MC, Epstein MJ, Cleveland SS, Wang H, Maison SF. Toward a differential diagnosis of hidden hearing loss in humans. PLoS ONE. 2016 Sep; 11(9):e0162726.
doi: 10.1371/journal.pone.0162726.
41. Fontenot TE, Giardina CK, Fitzpatrick DC. A model-based approach for separating the cochlear micro-phonic from the auditory nerve neurophonic in the ongoing response using electrocochleography. Front Neurosci. 2017 Oct 23;11:592. doi: 10.3389/fnins.2017.00592.
42. Durrant JD, Wang J, Ding DL, Salvi RJ. Are inner or outer hair cells the source of summating potentials recorded from the round window? J Acoust Soc Am. 1998 Jul; 104(1): 370–377. doi: 10.1121/1.423293.
43. Pappa AK, Hutson KA, Scott WC, et al. Hair cell and neural contributions to the cochlear summating poten-tial. J Neurophysiol. 2019 Jun 1; 121(6): 2163–2180. doi: 10.1152/jn.00006.2019. Epub 2019 Apr 3.
44. Snyder RL, Schreiner CE. The auditory neurophonic: Basic properties. Hear Res. 1984 Sep; 15(3): 261–280. doi:10.1016/0378-5955(84)90033-9.
45. Henry KR. Auditory nerve neurophonic recorded from the round window of the Mongolian Gerbil. Hear Res. 1995 Oct, 90(1-2): 176–184. doi:10.1016/0378-5955(95)00162-6.
46. Lichtenhan JT, Cooper NP, Guinan JJ Jr. A new audi-tory threshold estimation technique for low frequen-cies: proof of concept. Ear Hear. 2013 Jan-Feb;34(1), 42–51. doi: 10.1097/AUD.0b013e31825f9bd3.
47. Forgues M, Koehn HA, Dunnon AK, et al. Distinguish-ing hair cell from neural potentials recorded at the round window. J Neurophysiol. 2014 Feb;111(3):580-593.
doi: 10.1152/jn.00446.2013. Epub 2013 Oct 16.
48. Bester C, O'Leary SJ, Venail F., et al. Improving real-time feedback during cochlear implantation: The au-ditory nerve neurophonic/cochlear microphonic ratio. Ear Hear. 2025 May-Jun; 46(3):687-695. doi:10.1097/AUD.0000000000001613. Epub 2025 Jan 10.
49. Santarelli R, del Castillo I, Cama E, Scimemi P, Starr A. Audibility, speech perception and processing of temporal cues in ribbon synaptic disorders due to OTOF mutations. Hear Res. 2015 Dec;330(Pt B):200-212. doi: 10.1016/j.heares.2015.07.007. Epub 2015 Jul 15.
50. Khimich D, Nouvtan R, Pujol R, et al. Hair cell synap-tic ribbons are essential for synchronous auditory sig-naling. Nature. 2005 Apr 14;434(7036), 889–894. doi: 10.1038/nature03418. PMID: 15829963.
51. Buran BN, Strenzke N, Neef A, Gundelfinger ED, Moser T, Liberman MC. Onset coding is degraded in auditory nerve fibers from mutant mice lacking syn-aptic ribbons. J Neurosci. 2010 Jun 2;30(22):7587-7597. doi: 10.1523/jneurosci.0389- 10.2010.
52. Wichmann C, Moser T. Relating structure and function of inner hair cell ribbon synapses. Cell Tissue Res. 2015 Jul;361(1):95-114. doi: 10.1007/s00441-014-2102-7. Epub 2015 Jan 22.
53. Riggs WJ, Roche JP, Giardina CK, et al. Intraopera-tive electrocochleographic characteristics of auditory neuropathy spectrum disorder in cochlear implant subjects. Front Neurosci. 2017 Jul 19;11:416. doi: 10.3389/fnins.2017.00416.
54. Teagle HF, Roush PA, Woodard JS, et al. Cochlear implantation in children with auditory neuropathy spectrum disorder. Ear Hear. 2010 Jun;31(3):325-335.
doi: 10.1097/AUD.0b013e3181ce693b.
55. Roush P, Frymark T, Venediktov R, Wang B. Audio-logic management of auditory neuropathy spectrum disorder in children: A systematic review of the liter-ature. Am J Audiol. 2011 Dec; 20(2):159-170. doi:10.1044/1059-0889(2011/10-0032.
56. Rance G, Barker EJ. Speech perception in children with auditory neuropathy/dyssynchrony managed with either hearing AIDS or cochlear implants. Otol Neurotol. 2008 Feb;29(2):179-182. doi: 10.1097/mao.0b013e31815e92fd.
57. Buchman CA, Roush PA, Teagle HF, Brown CJ, Zdan-ski CJ, Grose JH. Auditory neuropathy characteristics in children with cochlear nerve deficiency. Ear Hear. 2006 Aug;27(4):399-408. doi: 10.1097/01.aud. 0000224100.30525.ab.
58. Stuermer KJ, Beutner D, Foerst A, Hahn M, Lang-Roth R, Walger M. Electrocochleography in children with auditory synaptopathy/neuropathy: Diagnostic find-ings and characteristic parameters. Int J Pediatri Oto-rhinolaryngol. 2015 Feb; 79(2):139-145. doi:10.1016/j.ijporl.2014.11.025.
59. Budenz CL, Starr K, Arnedt C, Telian SA, Arts HA, El-Kashlan HK, Zwolan TA. Speech and language out-comes of cochlear implantation in children with iso-lated auditory neuropathy versus cochlear hearing loss. Otol Neurotol. 2013 Dec;34(9):1615-1621. doi: 10.1097/MAO.0b013e3182a1ab5b.
60. Breneman AI, Gifford RH, Dejong MD. Cochlear im-plantation in children with auditory neuropathy spec-trum disorder: Long-term outcomes. J Am Acad Audiol. 2012 Jan 1;23(1):5-17. doi:10.3766/jaaa.23.1.2.
61. Rance G, Beer DE, Cone-Wesson B, et al. Clinical findings for a group of infants and young children with auditory neuropathy. Ear Hear. 1999 Jun;20(3):238-252. doi: 10.1097/00003446-199906000-00006.
62. Santarelli R. Information from cochlear potentials and genetic mutations helps localize the lesion site in au-ditory neuropathy. Genome Med. 2010; 91:2-10. Doi:10.1186/gm212.
63. Rodriguez-Ballesteros M, Reynoso, Olarte M, et al. A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy. Hum Mutat. 2008 May 22; 29(6):823-831. doi.org/10.1002/humu.20708
64. He S, Shahsavarani BS, McFayden TC, et al. Respon-siveness of the electrically stimulated cochlear nerve in children with cochlear nerve deficiency. Ear Hear. 2018 Mar/Apr;39(2):238-250. doi: 10.1097/AUD.0000000000000467. PMID: 28678078; PMCID: PMC5748379.
65. Huang T, Santarelli R, Starr A. Mutation of OPA1 gene causes deafness by affecting function of audi-tory nerve terminals. Brain Res. 2009 Dec;1300: 97-104. doi:10.1016/j.brainres.2009.08.083. Epub 2009 Sep 3.
66. Fontenot TE, Giardina CK, Teagle HF, et al. Clinical role of electrocochleography in children with audito-ry neuropathy spectrum disorder. Int J Pediatr Oto-rhinolaryngol. 2017 Aug; 99:120-127.` doi:10.1016/j.ijporl.2017.05.026.
67. Zhan KY, Adunka OF, Eshraghi A, et al. Electrophysi-ology and genetic testing in the precision medicine of congenital deafness: A review. J Otol. 2021 Jan;16(1):40-46. doi: 10.1016/j.joto.2020. 07.003. Epub 2020 Aug 1.
68. Tavartkiladze GA, Bakhshinyan VV. Objective measures at different stages of cochlear implanta-tion: A Data Analysis. Med Res Arch. 2025;13(1). doi:10.18103/mra.v13i1.6171.
69. Brown CJ, Abbas PJ, Fryauf-Bertschy H, Kelsay D, Gantz BJ. Intraoperative and postoperative electri-cally evoked auditory brain stem responses in Nucle-us cochlear implant users: Implications for the fitting process. Ear Hear. 1994 Apr;15(2):168-176. doi: 10.1097/00003446-199404000-00006.
70. Seo YJ, Kwak C, Kim S, Park YA, Park KH, Han W. Update on Bone-Con¬duction Auditory Brainstem Re-sponses: A Review. J Audiol Otol. 2018 Apr; 22(2):53-58. doi:10.7874/jao.2017.00346.
71. Tavartkiladze G.A., Potalova L.A., Kruglov A.V., Be-lov O.A. Effect of stimulation parameters on electri-cally evoked auditory brainstem responses. Acta Otolaryngol (Stockh). 2000;120(2): 214-217. doi:10.1080/000164800750000946.
72. Minami S, Kaga K. EABR of inner ear malformation and cochlear nerve deficiency after cochlear implan-tation in children. In: Kaga K, ed. Cochlear Implanta-tion in Children with Inner Ear Malformation and Cochlear Nerve Deficiency. Springer Link; 2017:97-109. doi:10.1007/978-981-10-1400-0_8.
73. Lalayants M. Auditory neuropathy spectrum disorder: Genetic and electrophysiological testing for predict-ing rehabilitation outcomes after cochlear implanta-tion. Latest advances in cochlear implant technologies and related clinical applications. IntechOpen. 2023 Oct 4. Available from: http://dx.doi.org/10.5772/intechopen.110430.
74. Gibson WP, Sanli H. Auditory neuropathy: an up-date. Ear Hear. 2007 Apr;28(2 Suppl): 102S-106S. doi: 10.1097/AUD.0b013e3180315392.
75. McMahon CM, Patuzzi RB, Gibson WP, Sanli H. Fre-quency-specific electrocochleography indicates that presynaptic and postsynaptic mechanisms of audito-ry neuropathy exist. Ear Hear. 2008 Jun;29(3):314-25. doi: 10.1097/AUD.0b013e3181 662c2a.
76. Kaga K. ABRs and electrically evoked ABRs in chil-dren. In: Modern Otology and Neurotology. Tokyo: Springer; 2022. doi: 10.1007/978-4-431-54189-9_1.
77. Dziemba OC, Hocke T, Müller A, Kaftan H. Excitation characteristic of a bipolar stimulus for broadband stimulation in measurements of electrically evoked auditory potentials. Z Med Phys. 2018 Feb;28(1):73-77. doi: 10.1016/j.zemedi.2017.09.008. Epub 2017 Oct 18. PMID: 29054678.
78. Bayri Ulukan M, Ciprut A. Intracochlear electrococh-leography findings in cochlear implant recipients with auditory neuropathy spectrum disorder. Int J Pediatr Otorinolaryngol. 2023. 170: 111596. https://doi.org/10.1016/j.ijporl.2023.111596
79. Santarelli R, Scimemi P, La Morgia C, Cama E, Del Castillo I, Carelli V. Electrocochleography in auditory neuropathy related to mutations in the OTOF or OPA1 gene. Audiol Res. 2021 Nov 26;11(4):639-652. doi: 10.3390/audiolres11040059. PMID: 34940017; PMCID: PMC8698970.
80. Jeon JH, Bae MR, Song MH, Noh SH, Choi KH, Choi JY. Relationship between electrically evoked audito-ry brainstem response and auditory performance af-ter cochlear implant in patients with auditory neu-ropathy spectrum disorder. Otol Neurotol. 2013 Sep;34(7):1261-1266. doi: 10.1097/MAO.0b013e318291c632.