Auditory Dys-Synchrony of Infancy: Best Practices for Diagnosis, Monitoring and Guidance

1. Auditory Dys-Synchrony of Infancy: Best Practices for Diagnosis, Monitoring and Guidance • Marilyn Neault, Ph.D., CCC-A • February 19, 2004 Thanks to the audiology and otolaryngology staff at Children’s Hospital Boston

2. What is auditory dys-synchrony? • Presence of cochlear hair cell activity - cochlear microphonic in ABR - otoacoustic emissions (may disappear) • Absence of auditory nerve response - no Wave I (no compound action potential) - no ABR waves • Behavioral hearing discrepant from ABR - idiosyncratic, fluctuating responses - audiogram may range normal to profound

3. a.k.a. (also known as…) • Auditory neuropathy • Primary auditory neuropathy (Shivashankar) • Auditory dys-synchrony • Auditory neuropathy “sensu stricto” (Rapin and Gravel) • Peri-synaptic audiopathy • Persistent outer hair cell function (Not all the same – will break down into categories as we learn more) • Your entry?

4. Why do children with auditory dys-synchrony drive audiologists crazy? • Pure tone audiogram and ability to detect sounds in everyday life is often better than the absence of ABR would predict • Word recognition ability is worse than the pure tone audiogram would predict • Functional hearing ability fluctuates and may improve • Expected benefit from hearing aids rarely realized

5. Possible sites of abnormality • Inner hair cells • Synaptic junction between inner hair cells and auditory neurons • Dendrites • Spiral ganglion cells • Axons Heterogeneous disorder with different possible sites

6. Drawing from Takasaka (1993)

7. Other findings in auditory dys-synchrony • Absent acoustic (stapedial) reflexes • OAE’s, if present, are not suppressed by contralateral stimulation • Poor word recognition ability, especially in noise • Poor temporal resolution • Poor low frequency discrimination • Limited or no benefit from hearing aids

8. Concomitant conditions • Half of newborns have NICU histories • One-third of children (80% of adults) have other neuropathies • Sural nerve biopsy may show abnormal myelinization • Charcot-Marie-Tooth (hereditary sensorimotor neuropathy) • Friedrich’s Ataxia • More than one child in family may have auditory dys-synchrony with no concomitant conditions. Mutations in the otoferlin gene may be involved (Varga, J. Med Gen. 2003)

9. “Auditory Dys-Synchrony of Infancy” (“ADI”) • Manifestation of cochlear activity in response to sounds without evidence of neural synchrony, in infancy • Term implies neither etiology nor prognosis

10. Problems with ADI #1. Some get better, some do not, no way (yet) to predict outcome #2. Newborns with auditory dys- synchrony pass OAE screen

11. Parent’s viewpoint • “What kind of a mother would take ‘I don’t know yet if your baby will be able to use his hearing to understand speech’ for an answer?” • Why would they screen newborns with a method that misses my baby’s problem? • Nebulous diagnosis with unknown cause and unknown prognosis • Encourages shopping • Some audiologists not familiar with the condition • Conflicting opinions about use of hearing aids, FM amplification

12. Incidence of auditory dys-synchrony? From Sininger’s literature review: 3.1 / 1000 high risk infants 1/10 children with congenital hearing loss

13. R clicks 20dBHL R 4000Hz 20dBHL R 2000Hz 20dBHL R 1000Hz 20dBHL L clicks 20dBHL L 4000Hz 20dBHL L 2000Hz 20dBHL L 1000Hz 20dBHL 15ms 20ms Typical normal ABR tracings near threshold levels

14. Rarefaction clicks, 90 dBHL Condensation clicks, 90 dBHL 9 month old former 25 week premie, passed newborn OAE screen but parents think she has a hearing loss

15. Rarefaction clicks, 90 dBHL Condensation clicks, 90 dBHL

16. Responses to both polarities superimposed Alternating polarity (CM not observable) Rarefaction clicks, insert phone tubing pinched to check for stimulus artifact 90 dBHL click stimuli

17. 102 dBHL 90 dBHL 80 dBHL 70 dBHL 60 dBHL (Note that the cochlear microphonic does not have a longer latency at lower intensities)

18. Audiogram by Visual Reinforcement Audiometry with insert earphones, on the same day as the ABR. Tympanograms: normal, OAEs: absent bilaterally (though present at newborn screen).

19. Challenge to audiologists: • We need to test in such a way that we’ll see the auditory dys-synchrony of infancy (ADI) • We need to recognize the signs of ADI when they are staring us in the face (a prolonged CM in response to clicks is not just a stimulus artifact!) • We need not to overdiagnose ADI • CM followed by typical ABR waves is not ADI ---we all have cochlear microphonics! • Recognize other reasons why a child might have OAEs but act deaf

20. From an audiologist on a learning curve: • “Because the ABR response did not show polarity inversion when ipsilaterally and contralaterally recorded tracings were superimposed, there is no evidence of auditory neuropathy.” (huh?)

21. From another audiologist on a learning curve:(well, aren’t we all…) • “A polarity-inverting cochlear microphonic response was seen on superimposed rarefaction and condensation click tracings, indicating absence of auditory neuropathy.” (huh?)

22. N3 Potential in a toddler who is deaf May have vestibular origin Not a cochlear microphonic; NOT dys-synchrony Does not reverse polarity Does have a latency-intensity function

23. KNOW THYSTIMULUSARTIFACT

24. Stimulus artifact generated by insert earphone and recorded by ABR electrodes

25. 1000Hz, 100dBHL, single polarity stimulus Overlaid ABR stimulus artifacts from 1000Hz tone bursts, recorded from joined electrodes (no head) and from a profoundly deaf infant.

26. Why did we not see auditory dys-synchrony pre-1990’s? • We did -- we just didn’t know it • Reports of patients with ABR results poorer than behavioral audiogram appeared by 1979 • By mid-1990’s, widespread availability of otoacoustic emissions equipment AND use of insert earphones for ABR testing (insert earphones allow observation of cochlear microphonic response in patients with absent ABR)

27. How do children with auditory dys-synchrony present to the audiology clinic? • Referred on newborn ABR hearing screen • Passed newborn OAE hearing screen but parents suspect child is deaf • A few may have passed ABR screen but then developed auditory dys-synchrony, or had a false negative result on their screen • Toddler with delayed receptive language development seen for VRA (WE NEED TO TEST ACOUSTIC REFLEXES FOR THESE CHILDREN) • Older hearing aid user with fluctuating hearing levels and limited hearing aid benefit for degree of loss

28. Joint Committee on Infant HearingYear 2000 Position Statement • Acknowledges that cases of auditory dys-synchrony may be missed by accepted screening protocols • Diagnostic audiology protocol includes ways to detect auditory dys-synchrony • Problem: auditory dys-synchrony cases may not reach diagnostic evaluation if screened by OAE

29. What should a UNHS program do about auditory dys-synchrony? • Analyze the consequences of doing automated ABR rather than either ABR or OAE for initial screening? (auditory dys-synchrony passes OAE screen at birth) • Educate audiologists to look for it • Educate early intervention providers: • Nature of parent experience • Typical behaviors of the children • Communication and therapy methods • Approach toward hearing aids and cochlear implant issues

30. Audiological / Educational Management of Infants with Auditory Dys-synchrony • Benefit from visual language system • Encourage speechreading (lipreading) • Some (about 50%) benefit from hearing aids; • perhaps in one ear • Beware of hair cell damage from hearing aid amplification, at least while OAEs are present • Consider sound field FM amplification • Language stimulation in quiet background; acoustic highlighting • Monitor behavioral audiogram and OAEs; “hearing” may improve or decline

31. Try a hearing aid or not? • Beware of hair cell damage if OAEs are still present. Presence of OAEs suggests normal cochlear amplifier function. • If OAEs have disappeared, try testing speech perception in each ear separately at elevated intensities. If the child understands words better at a higher than conversational intensity, try a hearing aid in that ear (or ears).

32. Audiological / Educational Management of Infants with Auditory Dys-synchrony, continued • Let parents know that a cochlear implant may help, if hearing does not improve and hearing aids don’t help • Help connect parents with other parents of children with the same condition

33. Auditory Neuropathy Information Homepage(with links including parent listserv) http://auditoryneuropathy.com

34. Why might a CI help a child with auditory dys-synchrony? • The child’s auditory nerve cells do not fire in tempo with incoming sounds. • The cochlear implant may act as a drill sergeant for auditory nerve fibers, stimulating them to fire in synchrony and to keep tempo with incoming sounds.

35. “Problem solving is an important skill in any professional, yet it can be counter-productive if applied too early in a goal-setting endeavor, especially if done for the family rather than with them.” D. Bailey

36. Typical candidacy to benefit from a cochlear implant • Age 12 months and up with profound bilateral hearing loss • OR age 25 months and up with severe or profound hearing loss and poor ability to recognize words through hearing aids “profound” means average hearing thresholds >90dBHL at 500, 1000 and 2000Hz, unaided; “severe” means 70-90dBHL, unaided; “poor” means no more than 30% correct repetition of one-syllable word list without clues at 57dBHL, with terrific hearing aids

37. Cochlear implant candidacy for a child with auditory dys-synchrony • Same as “typical” candidacy EXCEPT: • Allow enough time to know whether hearing will improve or even recover • Pure tone hearing levels are not the determining factor; a child may show a mild-moderate loss on the audiogram but may still benefit from a cochlear implant, if the child can not learn to recognize words without looking • Assess the reason for the condition, to assess the risk that the auditory nerve is truly “patholo-gical” or may deteriorate in function over time

38. Is anything different about the CI candidacy workup for a child with auditory dys-synchrony? • Should have MRI of the inner ears / auditory nerve (not just a CT scan). Consider MRI of the whole brain as well. • Should be evaluated by a neurologist for other peripheral neuropathies • Should monitor functional use of hearing in case ADI is resolving • Should have ABR, OAE, acoustic reflex tests repeated just prior to surgery • Consider Auditory Steady State Response (ASSR) to assist in ear determination • As for any CI candidate, parents should accept that outcomes are variable and not always predictable.

39. What do you have to lose?(by implanting a child with auditory dys-synchrony) • Ability to hear in the implanted ear when not using the speech processor • Ability to determine the extent to which hearing may improve or resolve on its own • Any ability the child might have had to localize the direction of a sound source

40. What do you have to gain?(by implanting a child with auditory dys-synchrony) • Likelihood of auditory synchrony on one side • Likelihood of stable hearing • Potential to learn to recognize spoken words and sentences in quiet without looking • Byproducts of better hearing: better speech and better language

41. Why might someone with auditory dys-synchrony have a particularly good CI outcome? • Language base in visual language system prior to CI; may not have been severely language-deprived prior to implant. • Has had and will have intense therapy and vigilant attention to communication. • Most have had some auditory experience prior to implant. • ?? May have cellular or neural elements in the cochlea in better supply than in some types of sensorineural hearing loss??

42. Why might someone with auditory dys-synchrony have a particularly limited CI outcome? • Cochlear implant may not succeed in driving the auditory nerve fibers to fire in synchrony. • If a degenerative nerve condition is present, such as in some mitochondrial disoders, performance with the CI could decline over time. • Child may have other challenges which would have made it difficult for him to learn to understand speech and to speak, even if he had had normal hearing.

43. BEFORE Pure tone audiogram mild to profound, fluctuating, moderately severe most common. No nerve action potential (Wave I). No ABR response. No acoustic reflexes. AFTER Sound field pure tone audiogram predictable at about 30dBHL, 250-6000Hz. Nerve action potential seen on neural response telemetry. EABR response + Acoustic reflex stimulable using cochlear implant. Before and after CI with auditory dys-synchrony

44. V v Electrically evoked Auditory Brainstem Response stimulated through the cochlear implant in the operating room

45. Electrically elicited acoustic reflex stimulated by presenting a signal through the cochlear implant

46. Models of auditory dys-synchrony • Temporal bones of expired premies with outer hair cells but no inner hair cells (Amatuzzi et al., Arch. Oto. HNS 2001) • Carboplatin causes selective loss of inner hair cells (but have acoustic reflexes) • Mouse strain with no inner hair cells • Mouse strain with early degeneration of cells that support the spiral ganglion cells

47. Research questions: • Need better way to differentiate which cases will improve or resolve • Catalog and monitor our series • Serial test measures • Infant auditory development scales • Additional electrophysiological measures? • Some patients have ASSR and some have cortical auditory evoked potentials, despite absence of ABR

48. Research questions • Can people with auditory dys-synchrony localize sound? • Does ABR or ASSR improve as pure tone audiogram and functional use of hearing improve? • Is true resolution possible? (study “resolved” cases for acoustic reflexes, gap detection, discrimination in noise) • Performance with cochlear implants • What happens to the unimplanted ear over time?

49. Neault and Kenna (study in progress,2004) Subjects: • 50 children with ADI whose hearing loss was evident during the first few months of life, seen at Children’s Hospital Boston • Excluded: later onset auditory dys-synchrony

50. Unilateral vs. Bilateral Of 50 children with ADI as of 2/04, 40(80%) with bilateral ADI (14 of these now have cochlear implants) 8(16%) with one ear ADI, one ear normal hearing 2(4%) with one ear ADI, one ear typical sensorineural hearing loss (one now has a cochlear implant)