Auditory Neuropathy Spectrum Disorder - National Center for ...

Auditory Neuropathy
Spectrum Disorder
Yvonne S. Sininger PhD
Professor of Head & Neck Surgery
University of California Los Angeles
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Financial Disclosure Information
I have no relevant financial relationship with the
manufacturers of any commercial products and/or
provider of commercial services discussed in this CME
activity.
I do not intend to discuss an unapproved/investigative
use of a commercial product/device in my presentation.
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What is it?
Audiologic Signs
• Hearing thresholds from normal to profound
deafness
• Auditory Brainstem Response absent or
abnormal.
• Present (prominent) Cochlear Microphonic.
• Otoacoustic Emissions usually present.
• Speech perception poorer than predicted by
audiogram
• Absent middle ear muscle ear reflexes.
3

Count
7
6
5
4
3
2
1
0
Auditory Neuropathy in Children
< 2 Years of Age
--Mild----Moderate----Severe--Profound
1 0 3 0 5 0 7 0 9 0 1 1 0
P T A
4

dB Hearing Level (ANSI, 1996)
-10
0
10
20
30
40
50
60
70
80
90
100
110
120
COCHLEAR
MICROPHONIC
AUDIOGRAM
250 500 1000 2000 4000 8000
Frequency (Hz)
CZ -> IPSI
CZ -> IPSI
0
5
Female 16 months
10
ms
Auditory Brainstem Response
Click 80 dBnHL
15
KC
Rarefaction & Condensation
20
5

PB Max
120
100
Speech Discrimination re PTA
80
60
40
20
0
-20
-20 0 20 40 60 80 100 120
PTA 2 (1000, 2000, 4000 Hz)
Neuropathy Speech Discrimination Score
Expected Speech Discrimination Score
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Potential Sites of Lesion in AN
Based on Symptoms
CM present from either
IHC OHC or both
OAE (outer hair cells)
Functioning
Inner hair cell function
or synapse could be
involved.
ABR Wave I Abnormal Abnormal-
(Peripheral Auditory
Nerve Involved (?)

Evidence of Auditory Nerve
Involvement in Auditory Neuropathy
Starr et al., found 30 30-40% 40% of patients have
evidence of other peripheral nerves disorders
(absent deep tendon reflexes or poor nerve
conduction)
As many as 80% of adult AN patients have subtle
or pronounced peripheral neuropathy (HSMN,
Friedreich’s Ataxia).
Sural nerve biopsy on 4 patients with AN shows
peripheral nerve disease, primarily axonal.
8

Evidence of Auditory Nerve
Involvement in Auditory Neuropathy
Human temporal bone histology showing
normal complement of hair cells with poor
ganglion cell survival (Spoendlin, Nadol).
Temporal bone histology on patient with
documented AN shows axonal degeneration
(95% loss of ganglion cells), with a normal
complement of hair cells (30% loss of OHC in
apical turn). Starr et al., Brain 2003
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Inner Hair Cells from Temporal Bone
of Auditory Neuropathy Patient
Starr et al., Brain 2003
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Sedigheh Delmaghani, et al. Nature Genetics 38, (2006)
Mutations in the
gene encoding
pejvakin pejvakin, , a newly
identified protein of
the afferent
auditory pathway,
cause DFNB59
auditory
neuropathy
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Buchman, CA, Roush, PA, Teagle, HF, et al. (2006).
Auditory neuropathy characteristics in children with
cochlear nerve deficiency. Ear and hearing, 27(4), 399 399-408. 408.
Nine (18%) of 51 children with ABR
characteristic of AN have been identified
as having small (N = 2; 4%) or absent (N
= 7; 14%) cochlear nerves on MRI.
RESULTS: Of the nine children with
cochlear nerve deficiency, five (56%)
were affected unilaterally and four (44%)
bilaterally.
13

Rodriguez-Ballesteros M et al (2003) Auditory Neuropathy in
Patients Carrying Mutations in the Otoferlin Gene (OTOF). Human
Mutation 22:451-456.
National Academy of Science
OTOF mutations
can explain 3.5% of
non non- syndromic syndromic
deafness.
Otoferlin involved
in vesicle vesicle-membrane membrane
fusion.
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Summary of sites of lesion in ANSD
with solid evidence
Auditory Nerve
neuropathy or insufficiency
Inner Hair Cell/auditory nerve synapse
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Consequences of Neural Involvement
• ANSD is known for fluctuations in symptoms:
remission, true fluctuations, and/or progression.
• Poor and inconsistent encoding of temporal
information lead to unusual temporal processing
and poor speech perception.
• Noise is even more disruptive to auditory/speech
perception than seen in other types of loss.
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History Factors in Auditory Neuropathy
N=59
(Sininger, Starr & Oba)
3 Dominant Family History
7 Multiple Risk Factors
7 Premature Birth
8 Hyperbillirubinemia
17 Recessive Family History
26 No Known Risk Factors
17

Management of Children with ANSD
28%
Assistive Listening Devices
N = 140
31%
35%
6%
CI (49)
CI + HA (8)
HA (44)
NAD (39)
From Pat Roush U. North Carolina
Complicated by difficulty in audiometrics
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Half of Subjects with Hearing Aids
show significant improvement.
Rance et al., E&H 2002
19

T and C Levels and NRT Thresholds are the Same for
AN Patients and Controls
Peterson, Shallop, et al al.
20

Electrical stimulation “reintroduces” timing precision
and synchrony, demonstrated in an electrical ABR
Peterson, Shallop, et al al.
21

UNC AN Children with CI N=49
35%
15%
CI in AN EAR
21%
29%
From Pat Roush U. North Carolina
2 yrs of use)
N=13
Limited Open Set (

Rehabilitation Strategies for
Children with ANSD
Significant individual variability is seen across
patients.
Rehabilitation strategy may need to incorporate
and emphasize visual information.
Delays in obtaining audiometric information is
common.
Persistent, frequent monitoring of hearing and
communication ability is recommended.
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Thanks for Listening
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