, Volume 54, Issue 11, pp 833–841 | Cite as

Diagnostik und Therapie der auditorischen Synaptopathie/Neuropathie

  • T. Moser
  • N. Strenzke
  • A. Meyer
  • A. Lesinski-Schiedat
  • T. Lenarz
  • D. Beutner
  • A. Foerst
  • R. Lang-Roth
  • H. von Wedel
  • M. Walger
  • M. Gross
  • A. Keilmann
  • A. Limberger
  • T. Steffens
  • J. Strutz


Die audiologische Konstellation von pathologischen frühen akustisch evozierten Potenzialen (fehlend, erhöhte Schwelle und gestörte Kurvenform) trotz nachweisbarer otoakustischer Emissionen geht häufig mit einer von schlechtem Sprachverständnis geprägten Schwerhörigkeit bzw. mit Taubheit einher. Diese als auditorische Neuropathie erstbeschriebene, heterogene Erkrankungsgruppe beinhaltet peripher-auditorische Störungen der synaptischen Schallkodierung durch innere Haarzellen (Synaptopathie) und/oder der Erregungsbildung und -weiterleitung im Hörnerv (Neuropathie). Dieses Konsensuspapier gibt aktuelle Hintergrundinformationen sowie Empfehlungen zur Diagnostik und Therapie im deutschsprachigen Raum. Es nimmt dabei Bezug auf aktuelle internationale Statements.


Synaptopathie Neuropathie Taubheit Sprachverständnis 

Diagnosis and therapy of auditory synaptopathy/neuropathy


Pathological auditory brainstem responses (lack of responses, elevated thresholds and perturbed waveforms) in combination with present otoacoustic emissions are typical audiometric findings in patients with a hearing impairment that particularly affects speech comprehension or complete deafness. This heterogenous group of disorders first described as “auditory neuropathy” includes dysfunction of peripheral synaptic coding of sound by inner hair cells (synaptopathy) and/or of the generation and propagation of action potentials in the auditory nerve (neuropathy). This joint statement provides prevailing background information as well as recommendations on diagnosis and treatment. The statement focuses on the handling in the german language area but also refers to current international statements.


Synaptopathy Neuropathy Deafness Speech recognition 


  1. 1.
    Amatuzzi MG, Northrop C, Liberman MC et al. (2001) Selective inner hair cell loss in premature infants and cochlea pathological patterns from neonatal intensive care unit autopsies. Arch Otolaryngol Head Neck Surg 127: 629–636CrossRefPubMedGoogle Scholar
  2. 2.
    Berlin CI, Hood LJ, Cecola RP et al. (1993) Does type I afferent neuron dysfunction reveal itself through lack of efferent suppression? Hear Res 65: 40–50CrossRefPubMedGoogle Scholar
  3. 3.
    Berlin CI, Bordelon J, St John P et al. (1998) Reversing click polarity may uncover auditory neuropathy in infants. Ear Hear 19: 37–47CrossRefPubMedGoogle Scholar
  4. 3a.
    Berlin CI, Hood L, Morlet T, Rose K, Brashears S (2003) Auditory neuropathy/dys-synchrony: diagnosis and management. Ment Retard Dev Disabil Res Rev 9: 225–231CrossRefPubMedGoogle Scholar
  5. 4.
    Berlin CI, Hood LJ, Morlet T 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: 546–553CrossRefPubMedGoogle Scholar
  6. 5.
    Brandt A, Striessnig J, Moser T (2003) CaV1.3 channels are essential for development and presynaptic activity of cochlear inner hair cells. J Neurosci 23: 10832–10840PubMedGoogle Scholar
  7. 6.
    Campbell PE, Harris CM, Sirimanna T, Vellodi A (2003) A model of neuronopathic Gaucher disease. J Inherit Metab Dis 26: 629–639CrossRefPubMedGoogle Scholar
  8. 7.
    Colletti V, Carner M, Miorelli V et al. (2005) Auditory brainstem implant (ABI): new frontiers in adults and children. Otolaryngol Head Neck Surg 133(1): 126–138CrossRefPubMedGoogle Scholar
  9. 8.
    Comi G (1997) Evoked potentials in diabetes mellitus. Clin Neurosci 4: 374–379PubMedGoogle Scholar
  10. 9.
    Ding DL, Wang J, Salvi R, Henderson D et al. (1999) Selective loss of inner hair cells and type-I ganglion neurons in carboplatin-treated chinchillas. Mechanisms of damage and protection. Ann N Y Acad Sci 884: 152–170CrossRefPubMedGoogle Scholar
  11. 10.
    Dou H, Vazquez AE, Namkung Y et al. (2004) Null mutation of alpha1D Ca2+ channel gene results in deafness but no vestibular defect in mice. J Assoc Res Otolaryngol 5: 215–226CrossRefPubMedPubMedCentralGoogle Scholar
  12. 11.
    Foerst A, Beutner D, Lang-Roth R et al. (2006) Prevalence of auditory neuropathy/synaptopathy in profound hearing impaired children. Int J Pediatr Otorhinolaryngol 70(8): 1415–1422CrossRefPubMedGoogle Scholar
  13. 12.
    Fujikawa S, Starr A (2000) Vestibular neuropathy accompanying auditory and peripheral neuropathies. Arch Otolaryngol Head Neck Surg 126: 1453–1456CrossRefPubMedGoogle Scholar
  14. 13.
    Henry WR, Mulroy MJ (1995) Afferent synaptic changes in auditory hair cells during noise-induced temporary threshold shift. Hear Res 84: 81–90CrossRefPubMedGoogle Scholar
  15. 14.
    Hoth S, Lenarz T (1994) Elektrische Reaktionsaudiometrie. Springer, Berlin Heidelberg New York TokioGoogle Scholar
  16. 15.
    Katada A, Nonaka S, Harabuchi Y (2005) Cochlear implantation in an adult patient with auditory neuropathy. Eur Arch Otorhinolaryngol 262: 449–452CrossRefPubMedGoogle Scholar
  17. 16.
    Keilmann A, Rühl S, Lenarz T, Lesinski-Schiedat A (2005) Erfolg der Cochlea-Implantation bei perisynaptischer Audiopathie – auditorischer Neuropathie, ein Matched-pairs-Vergleich. Z Audiol 44: 10–18Google Scholar
  18. 17.
    Khedr EM, El Toony LF, Tarkhan MN, Abdella G (2000) Peripheral and central nervous system alterations in hypothyroidism: electrophysiological findings. Neuropsychobiology 41: 88–94CrossRefPubMedGoogle Scholar
  19. 18.
    Khimich D, Nouvian R, Pujol R et al. (2005) Hair cell synaptic ribbons are essential for synchronous auditory signalling. Nature 434: 889–894CrossRefPubMedGoogle Scholar
  20. 18a.
    Koyama S, Kaga K, Sakata H, Iino Y, Kodera K (2005) Pathological findings in the temporal bone of newborn infants with neonatal asphyxia. Acta Otolaryngol 125: 1028–1032CrossRefPubMedGoogle Scholar
  21. 19.
    Kumar AU, Jayaram M (2005) Auditory processing in individuals with auditory neuropathy. Behav Brain Funct 1: 21CrossRefPubMedPubMedCentralGoogle Scholar
  22. 20.
    Lacas-Gervais S, Guo J, Strenzke N et al. (2004) BetaIVSigma1 spectrin stabilizes the nodes of Ranvier and axon initial segments. J Cell Biol 166: 983–990CrossRefPubMedPubMedCentralGoogle Scholar
  23. 21.
    Lesinski-Schiedat A, Frohne C, Hemmaouil I et al. (2001) [Subjective deafness in case of peri-synaptic audiopathy. Isolated defects of the inner hair cells?]. Laryngorhinootologie 80: 601–604CrossRefPubMedGoogle Scholar
  24. 22.
    Lesinski-Schiedat A, Illg A, Warnecke A et al. (2005) [Paediatric cochlear implantation in the first year of life: Preliminary results.]. HNO 54(7): 565–572CrossRefGoogle Scholar
  25. 23.
    Lenarz T (1998) Cochlea-Implantate. Springer, Berlin Heidelberg New York TokioGoogle Scholar
  26. 24.
    Madden C, Hilbert L, Rutter M et al. (2002) Pediatric cochlear implantation in auditory neuropathy. Otol Neurotol 23: 163–168CrossRefPubMedGoogle Scholar
  27. 25.
    Mason JC, De Michele A, Stevens C et al. (2003) Cochlear implantation in patients with auditory neuropathy of varied ethiologies. Laryngoscope 113: 45.49CrossRefPubMedGoogle Scholar
  28. 26.
    Michalewski HJ, Starr A, Nguyen TT et al. (2005) Auditory temporal processes in normal-hearing individuals and in patients with auditory neuropathy. Clin Neurophysiol 116: 669–680CrossRefPubMedGoogle Scholar
  29. 26a.
    Migliosi V, Modamio-Hoybjor S, Moreno-Pelayo MA et al. (2002) Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss. J Med Genet 39:502–506CrossRefPubMedPubMedCentralGoogle Scholar
  30. 26b.
    Mirghomizadeh F, Pfister M, Apaydin F et al. (2002) Substitutions in the conserved C2C domain of otoferlin cause DFNB9, a form of nonsyndromic autosomal recessive deafness. Neurobiol Dis 10:157–164CrossRefPubMedGoogle Scholar
  31. 27.
    Oysu C, Aslan I, Basaran B, Baserer N (2001) The site of hearing loss in Refsum’s disease. Int J Pediatr Otorhinolaryngol 61: 129–134CrossRefPubMedGoogle Scholar
  32. 28.
    Parkinson NJ, Olsson CL, Hallows JL et al. (2001) Mutant beta-spectrin 4 causes auditory and motor neuropathies in quivering mice. Nat Genet 29: 61–65CrossRefPubMedGoogle Scholar
  33. 29.
    Peterson A, Shallop J, Driscoll C et al. (2003) Outcomes of cochlear implantation in children with auditory neuropathy. J Am Acad Audiol 14: 188–201PubMedGoogle Scholar
  34. 30.
    Platzer J, Engel J, Schrott-Fischer A et al. (2000) Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels. Cell 102: 89–97CrossRefPubMedGoogle Scholar
  35. 31.
    Puel J, Safieddine S, d’Aldin G et al. (1995) Synaptic regeneration and fuctional recovery after excitotoxic injury in the guinea pig cochlea. C R Acad Sci 318: 67–75Google Scholar
  36. 32.
    Rance G, Beer DE, Cone-Wesson B et al. (1999) Clinical findings for a group of infants and young children with auditory neuropathy. Ear Hear 20: 238–252CrossRefPubMedGoogle Scholar
  37. 33.
    Rapin I, Gravel J (2003) „Auditory neuropathy“: physiologic and pathologic evidence calls for more diagnostic specificity. Int J Pediatr Otorhinolaryngol 67: 707–728CrossRefPubMedGoogle Scholar
  38. 33a.
    Rask-Andersen H, Ekvall L, Scholtz A, Schrott-Fischer A (2000) Structural/audiometric correlations in a human inner ear with noise-induced hearing loss. Hear Res 141: 129–139CrossRefPubMedGoogle Scholar
  39. 34.
    Rodriguez-Ballesteros M, del Castillo FJ, Martin Y et al. (2003) Auditory neuropathy in patients carrying mutations in the otoferlin gene (OTOF). Hum Mutat 22: 451–456CrossRefPubMedGoogle Scholar
  40. 35.
    Rouillon I, Marcolla A, Roux I et al. (2006) Results of cochlear implantation in two children with mutations in the OTOF gene. Int J Pediatr Otorhinolaryngol 70: 689–696CrossRefPubMedGoogle Scholar
  41. 35a.
    Roux I, Safieddine S, Nouvian R et al. (2006) Otoferlin, defective in DFNB9 deafness, is essential for the Ca2+-triggered synaptic exocytosis at the auditory hair cell ribbon synapse. Cell: (in press)Google Scholar
  42. 36.
    Scaioli V, Pareyson D, Avanzini G, Sghirlanzoni A (1992) F response and somatosensory and brainstem auditory evoked potential studies in HMSN type I and II. J Neurol Neurosurg Psychiatry 55: 1027–1031CrossRefPubMedPubMedCentralGoogle Scholar
  43. 37.
    Sheykholeslami K, Kaga K, Murofushi T, Hughes DW (2000) Vestibular function in auditory neuropathy. Acta Otolaryngol 120: 849–854CrossRefPubMedGoogle Scholar
  44. 38.
    Sheykholeslami K, Schmerber S, Habiby Kermany M, Kaga K (2005) Sacculo-collic pathway dysfunction accompanying auditory neuropathy. Acta Otolaryngol 125: 786–791CrossRefPubMedGoogle Scholar
  45. 39.
    Sininger Y, Oba S (2001) Patients with auditory neuropathy: Who are they and what can they hear? In: Sininger YS, Starr A (eds) Auditory neuropathy: a new perspective on hearing disorders: Singular Thomson Learning. pp 15–35Google Scholar
  46. 40.
    Sininger Y (2002) Identification of auditory neuropathy in infants and children. Semin Hear 23: 193–200CrossRefGoogle Scholar
  47. 40a.
    Spoendlin H (1971) Degeneration behaviour of the cochlear nerve. Arch Klin Exp Ohren Nasen Kehlkopfheilkd 200: 275–291CrossRefPubMedGoogle Scholar
  48. 40b.
    Spoendlin H (1984) Factors inducing retrograde degeneration of the cochlear nerve. Ann Otol Rhinol Laryngol Suppl 112: 76–82PubMedGoogle Scholar
  49. 41.
    Starr A, Picton TW, Sininger Y et al. (1996) Auditory neuropathy. Brain 119: 741–753CrossRefPubMedGoogle Scholar
  50. 42.
    Starr A, Isaacson B, Michalewski HJ et al. (2004) A dominantly inherited progressive deafness affecting distal auditory nerve and hair cells. J Assoc Res Otolaryngol 5: 411–426CrossRefPubMedPubMedCentralGoogle Scholar
  51. 43.
    Starr A, Zeng FG, Michalewski HJ, Moser T (2006) Perspectives on auditory neuropathy: disorders of inner hair cell, auditory nerve and their synapse. In: Dallos P (ed) Handbook of the senses. (in press)Google Scholar
  52. 44.
    Sutton A, Gravel J, Hood L et al. (2004) Assessment and management of auditory neuropathy/auditory dys-synchrony. A recommended protocol.
  53. 44a.
    Varga R, Kelley PM, Keats BJ et al. (2003) Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene. J Med Genet 40: 45–50CrossRefPubMedPubMedCentralGoogle Scholar
  54. 44b.
    Varga R, Avenarius MR, Kelley PM et al. (2006) OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele. J Med Genet 43: 576–581CrossRefPubMedGoogle Scholar
  55. 45.
    Wang Q, Gu R, Han D, Yang W (2003) Familial auditory neuropathy. Laryngoscope 113: 1623–1629CrossRefPubMedGoogle Scholar
  56. 45a.
    Yasunaga S, Grati M, Cohen-Salmon M et al. (1999) A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness. Nat Genet 21: 363–369CrossRefPubMedGoogle Scholar
  57. 46.
    Zeng FG, Kong YY, Michalewski HJ, Starr A (2004) Perceptual consequences of disrupted auditory nerve activity. J Neurophysiol 93(6): 3050–3063CrossRefPubMedGoogle Scholar
  58. 47.
    Zhou R, Abbas PJ, Assouline JG (1995) Electrically evoked auditory brainstem response in peripherally myelin-deficient mice. Hear Res 88: 98–106CrossRefPubMedGoogle Scholar
  59. 48.
    Zhou R, Assouline JG, Abbas PJ et al. (1995) Anatomical and physiological measures of auditory system in mice with peripheral myelin deficiency. Hear Res 88: 87–97CrossRefPubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag 2006

Authors and Affiliations

  • T. Moser
    • 1
  • N. Strenzke
    • 1
  • A. Meyer
    • 1
  • A. Lesinski-Schiedat
    • 2
  • T. Lenarz
    • 2
  • D. Beutner
    • 3
  • A. Foerst
    • 3
  • R. Lang-Roth
    • 3
  • H. von Wedel
    • 3
  • M. Walger
    • 3
  • M. Gross
    • 4
  • A. Keilmann
    • 5
  • A. Limberger
    • 5
  • T. Steffens
    • 6
  • J. Strutz
    • 6
  1. 1.HNO-Universitätsklinik GöttingenGöttingenGermany
  2. 2.HNO-KlinikMedizinische Hochschule HannoverGermany
  3. 3.HNO-Universitätsklinik KölnGermany
  4. 4.Klinik für Audiologie und PhoniatrieCharité – Universitätsmedizin BerlinGermany
  5. 5.Univ.-Klinik für Kommunikationsstörungen MainzGermany
  6. 6.HNO-Universitätsklinik RegensburgGermany

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