Download Variation in auditory neuropathy spectrum disorder

Variation in Auditory Neuropathy Spectrum
Disorder: Implications for Evaluation and
Management
Linda J. Hood, Ph.D.1
ABSTRACT
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Auditory neuropathy spectrum disorder (ANSD) has an effect,
either directly or indirectly, on the neural processing of auditory stimuli.
Physiological measures are needed to accurately identify and assess
ANSD. Sound processing in patients with ANSD is highly variable,
and relationships between hearing sensitivity and ability to process
speech do not follow the typical hearing loss rules. Auditory function
may show changes over time, with progression or fluctuation, or may
remain stable. Considerable variation in presentation is observed across
patients of all ages and includes milder forms of ANSD. Based on these
observations, management should proceed with thorough assessment of
individual capabilities. It is important to distinguish between detection
(sensitivity) and discrimination of sound, especially in noise, when
evaluating function and benefit from various forms of management.
Visual information is important for most patients and cochlear implants
provide significant benefit when that option is selected. As the understanding of ANSD and the inherent variation among patients advances,
the knowledge and methods that we bring to our clinical practices
should allow us to more accurately characterize function and implement
appropriate management.
KEYWORDS: Auditory neuropathy, auditory dys-synchrony, auditory
neuropathy spectrum disorder, cochlear hair cell response, auditory
neural response
Learning Outcomes: As a result of this activity, the participant will be able to (1) identify the characteristics of
auditory neuropathy spectrum disorder and appreciate the variation among patients, and (2) make appropriate
recommendations for the management of patients with auditory neuropathy spectrum disorder.
1
Professor, Department of Hearing and Sciences;
Associate Director for Research, National Center for
Childhood Deafness; Vanderbilt University, Tennessee.
Address for correspondence and reprint requests: Linda
J. Hood, Ph.D., Associate Director for Research, National
Center for Childhood Deafness; Vanderbilt University,
Nashville, TN 37212 (e-mail: linda.j.hood@Vanderbilt.
edu).
Proceedings of the Widex Pediatric Audiology Congress;
Guest Editor, André M. Marcoux, Ph.D.
Semin Hear 2011;32:117–122. Copyright # 2011 by
Thieme Medical Publishers, Inc., 333 Seventh Avenue,
New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI: http://dx.doi.org/10.1055/s-0031-1277232.
ISSN 0734-0451.
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2011
P
atients with present cochlear responses
and absent/abnormal auditory brain stem responses (ABRs) are classified as having auditory neuropathy (AN),1 AN/dys-synchrony
(AD),2 or AN spectrum disorder (ANSD).3
Though these terms have somewhat different
intended meanings and origins, at present they
often are used interchangeably. More specific
and accurate descriptors will likely emerge with
better understanding of underlying mechanisms.
Clinical presentation in AN (AN/AD,
ANSD) typically involves inordinate difficulty
listening in noise, possible fluctuation in hearing over time, and/or delayed speech and language development. Some patients with
fluctuations in auditory responses accompanying elevated temperature are reported.4 Physiological responses are key factors in accurately
identifying and characterizing AN. Presence of
cochlear responses is documented by otoacoustic emissions (OAE) and cochlear microphonics. Neural responses are either directly
or indirectly affected, and abnormalities are
demonstrated by absent or highly abnormal
ABRs, middle ear muscle reflexes (MEMRs),
and medial olivocochlear reflexes (noted via
OAE suppression). Behavioral responses are
variable as shown by audiometric configurations from normal to profound ranges and
variable but generally poor speech recognition,
particularly in noise.
VARIATION AMONG PATIENTS
WITH ANSD
Variation is broad among ANSD patients.5,6
Factors related to variation include time of
onset, underlying mechanisms, genetics, possible risk factors, ability to understand speech,
and changes over time. Some patients display
no overt delays or auditory complaints until
adulthood or in some cases until, by chance,
MEMR or ABR testing is completed. Patients
at the other end of the continuum display an
apparent total lack of sound awareness, reflected in their severely affected communication and speech production abilities. However,
most ANSD patients fall between these two
extremes, showing inconsistent auditory responses with best responses in quiet and poor-
est in noise. Their audiograms can be
misleading or fluctuate. The ABR is desynchronized and middle-ear muscle reflexes
are absent or in some cases elevated.
These characteristics, and particularly their
variation, present the clinician with several
challenges. Accurate characterization of
ANSD includes understanding variation
among and within particular forms of ANSD
along with the ability to identify factors contributing to the variation. As our understanding of the underlying
mechanisms,
physiological responses, and genetic factors
improves, so should our ability to better characterize and distinguish among forms of
ANSD. More accurate characterization should
also have a positive impact on management
planning.
To understand the characteristics and variation of ANSD, we (the group at the Kresge
Hearing Research Laboratory) developed a
database of patients and recently summarized
data related to 260 of those patients.6 Most of
these patients are under 12 years of age, though
some adults also are included. The majority of
the patients are pediatric because these are the
groups who are actively being tested through
newborn hearing and school screening programs. We believe that there are adults with
ANSD who simply have not been identified.
Patients were included in the database
based on presence of OAEs (currently or at
some point in their history) and cochlear microphonics with absent or abnormal MEMRs
and ABRs. Review of OAE data showed that
76% of the patients had present OAEs when
the diagnostically definitive testing for AN/AD
was completed. About 16% had absent OAEs,
which in most cases was accompanied by abnormal middle-ear test results, and the remaining patients had partially present OAEs.
MEMRs were absent in 90% of patients.7
When MEMRs were elicited, none were normal; they were elevated or in combination with
elevated or absent responses at other frequencies. The medial olivocochlear reflex, measured
via suppression of OAEs, is also substantially
reduced or absent in patients with ANSD.8
Most patients have absent ABRs, though
some show responses only to high-intensity
stimuli. In our database, 75% of the ANSD
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patients had absent ABRs, and 25% showed
some evidence of neural responses. In these
cases, ABRs typically showed only low-amplitude wave V and, as noted earlier, only at
higher (i.e., 75 dB hearing level in normal
listeners for brief signals and above) intensities.
The variation among individuals in behavioral responses highlights the importance of
physiological responses in assessment and
makes management of ANSD particularly
challenging. Thresholds for tonal stimuli
(e.g., pure-tone audiometric thresholds) range
from normal to profound. Speech recognition
is typically poorer than seen in other forms of
hearing loss, though some patients display
quite good word recognition in quiet. All
ANSD patients tested thus far in our experience have very poor (i.e., poorer than expected
based on threshold sensitivity) speech understanding ability in noise.
As a part of our database analysis, we
summarized speech recognition ability for 68
subjects over the age of 4 years.6 Our rationale
for limiting the analysis to this age range
related to the ability to use standardized assessment measures. In this group, 38 of the 68
individuals had no word recognition ability for
monosyllables in quiet. Thus, the remainder of
the analysis focused on the remaining 30 subjects. Of those, 25 had measureable word
recognition only in quiet (i.e., 0% in noise).
Word recognition in quiet averaged 45% in
this group, with some patients having very poor
word recognition ability (i.e., < 20%) and
others quite good (i.e., > 80%). The five subjects of the original 30 with word recognition
ability in quiet and in noise are our best
performers and, despite quite good ability in
quiet, they still fall below those with other
forms of hearing loss in noise. These findings
are quite consistent with those reported by
Rance et al.9 Difficulty in understanding
speech has been linked to marked abnormalities observed on temporal processing tasks.10,11
The incidence of ANSD is 1 in 10
patients with desynchronized ABRs. This is
based on several studies that have included data
from newborn screening as well as evaluation of
children enrolled in schools for the deaf.12–15
Several factors have been explored in relation to
ANSD. In our database, 6.2% display unilat-
eral ANSD, with the majority having normal
hearing in the other ear. Some risk factors are
often seen in the history of individuals with
ANSD, and we and others have summarized
those.6,16,17
Several genetic mutations have been identified that are associated with ANSD.18,19
Families display recessive and dominant inheritance patterns, as well as some that are
likely mitochondrial in nature. ANSD occurs
alone, as in nonsyndromic recessive ANSD, as
well as part of a syndrome, such as hereditary
motor sensory neuropathies. Among the various genes linked to ANSD, OTOF mutations, responsible for production of the
protein otoferlin, with localized expression at
the inner hair cell synaptic juncture, have been
of particular interest.
IMPLICATIONS OF VARIABLE
FUNCTION FOR MANAGEMENT
OF PATIENTS WITH ANSD
Management of ANSD differs from typical
sensorineural hearing loss. In many cases, discrimination of sound is affected to a much
greater degree than detection of sound. For
example, some patients have quite good sound
detection with threshold sensitivity in the mild
hearing loss range but have very poor or no
word and sentence understanding.
Variation in clinical presentation is further
highlighted by differences among patients in
the effectiveness of various management approaches. Although some patients are reported
to demonstrate benefit from amplification, the
majority of patients with ANSD in our practices (Louisiana State University Health Sciences Center–New Orleans and Vanderbilt
University) have not been successful in using
amplification alone to facilitate the development of speech and language or general communication. We evaluate the effectiveness of
amplification in all of our ANSD patients who
demonstrate reduced threshold sensitivity to
sound. In our practice, we fit amplification
using targets based on behavioral thresholds,
which typically can be obtained at an age of
around 6 months. A key factor in assessing
benefit is separating improvement from detection of sound, where we typically observe
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2011
changes postfitting, from ability related to discrimination of sound. Because discrimination
of sound is necessary for communication and
speech and language development, we closely
follow each individual’s progress in assessing
the effectiveness of amplification.
Assistive listening (FM) devices are very
helpful, which is consistent with the particular
difficulty that ANSD patients experience in
noisy situations. The improved signal-to-noise
ratios provide a clearer signal to an auditory
system that cannot cope with interference.20 In
addition, use of visual information is strongly
encouraged in the management of ANSD
patients. Communication systems, such as
cued speech or sign languages, facilitate language development in infants and children.21
Both children and adults with ANSD
demonstrate improved speech perception and
significant benefit from cochlear implants.22–25
Despite variation among patients and early
reports of limited benefit, ANSD patients generally derive considerable benefit from cochlear
implants in improved hearing and speech perception abilities. As might be expected, more
favorable postimplantation speech perception
scores are reported for ANSD subjects with
normal cochlear nerves as compared with those
with cochlear nerve anomalies.26,27 Other techniques such as clear speech25 and envelope
enhancement28 show some promise in improving word recognition.
FUTURE NEEDS: ISSUES AND
CHALLENGES
Although our understanding of ANSD has
advanced, several issues and challenges remain.
The observed variation among patients highlights the importance of developing information and methods that will allow clinicians to
accurately distinguish among the various forms
of ANSD. Progress in this area will likely
include the development of methods that can
accurately distinguish normal from abnormal
function at inner hair cell, synaptic juncture,
and neural levels and the identification of
specific risk factors related to ANSD. Even
within various forms of ANSD, we expect
that variation will exist, and we need to understand the range of variation, the role of genetics
and variation within and among genetic mutations, and other contributing physiological and
environmental factors.
Another challenge in evaluating and managing ANSD in infants is distinguishing between neuromaturation of the auditory system,
where neural responses improve over the first
year or so of life, and true ANSD. Are there
characteristics of physiological responses, patient history, or other factors that can distinguish neuromaturation from ANSD? In infants
and children with ANSD, how can we predict
who will develop speech/language with minimal intervention despite poor neural synchrony
reflected in absent or highly abnormal ABRs?
In developing appropriate management strategies and an evidence base, guidelines are
needed for determination of appropriate recommendations and fitting practices for hearing
aids, frequency modulation systems, cochlear
implants, and appropriate use of various intervention strategies.
Studies of patients with ANSD have
demonstrated sensitivity of electrocochleography and compound action potential physiological responses from the cochlea and VIIIth
nerve in characterizing variation in function
among patients.29,30 Psychophysical tasks,
particularly those related to temporal resolution, and cortical responses provide insight
into underlying mechanisms and functional
abilities. Cortical evoked potentials also
show promise in characterizing auditory function objectively and in establishing links with
speech recognition.31,32
As future clinical assessment facilitates
greater use of novel stimuli and paradigms,
more sensitive approaches, and development
of clinically feasible methods that include these
advances, we should be able to more accurately
characterize and understand the variation we
observe in ANSD. This understanding also
should support more informed approaches to
patient management.
REFERENCES
1. Starr A, Picton TW, Sininger Y, Hood LJ, Berlin
CI. Auditory neuropathy. Brain 1996;119(Pt 3):
741–753
Downloaded by: SASLHA. Copyrighted material.
120
2. Berlin C, Hood L, Rose K. On renaming auditory
neuropathy as auditory dys-synchrony: implications for a clearer understanding of the underlying
mechanisms and management options. Audiology
Today 2001;13:15–17
3. Hayes D, Sininger YS. Identification and management of infants and young children with auditory
neuropathy spectrum disorder. Presented at: The
Newborn Hearing Systems Conference; June
19–21, 2008; Lake Como, Italy
4. Starr A, Sininger Y, Winter M, Derebery MJ,
Oba S, Michalewski HJ. Transient deafness due to
temperature-sensitive auditory neuropathy. Ear
Hear 1998;19(3):169–179
5. Starr A, Sininger YS, Pratt H. The varieties of
auditory neuropathy. J Basic Clin Physiol Pharmacol 2000;11(3):215–230
6. Berlin CI, Hood LJ, Morlet T, et al. Multi-site
diagnosis and management of 260 patients with
auditory neuropathy/dys-synchrony (auditory neuropathy spectrum disorder). Int J Audiol 2010;
49(1):30–43
7. Berlin CI, Hood LJ, Morlet T, et al. 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 2005;16(8):546–553
8. Hood LJ, Berlin CI, Bordelon J, Rose K. Patients
with auditory neuropathy/dys-synchrony lack
efferent suppression of transient evoked otoacoustic emissions. J Am Acad Audiol 2003;14(6):302–
313
9. Rance G, Barker E, Mok M, Dowell R, Rincon A,
Garratt R. Speech perception in noise for children
with auditory neuropathy/dys-synchrony type
hearing loss. Ear Hear 2007;28(3):351–360
10. Zeng FG, Oba S, Garde S, Sininger Y, Starr A.
Temporal and speech processing deficits in
auditory neuropathy. Neuroreport 1999;10(16):
3429–3435
11. Rance G, McKay C, Grayden D. Perceptual
characterization of children with auditory neuropathy. Ear Hear 2004;25(1):34–46
12. Berlin CI, Hood LJ, Morlet T, et al. The search for
auditory neuropathy patients and connexin 26
patients in schools for the deaf. ARO Abstracts
2000;23:23
13. Lee JSM, McPherson B, Yuen KCP, Wong LLN.
Screening for auditory neuropathy in a school for
hearing impaired children. Int J Pediatr Otorhinolaryngol 2001;61(1):39–46
14. 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;20(3):
238–252
15. Sininger YS. Auditory neuropathy in infants and
children: implications for early hearing detection
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
and intervention programs. Audiology Today
2002;14:16–21
Deltenre P, Mansbach AL, Bozet C, Clercx A,
Hecox KE. Auditory neuropathy: a report on three
cases with early onsets and major neonatal illnesses. Electroencephalogr Clin Neurophysiol
1997;104(1):17–22
Madden C, Rutter M, Hilbert L, Greinwald JHJr,
Choo DI. Clinical and audiological features in
auditory neuropathy. Arch Otolaryngol Head
Neck Surg 2002;128(9):1026–1030
Varga R, Kelley PM, Keats BJ, et al. Nonsyndromic recessive auditory neuropathy is the
result of mutations in the otoferlin (OTOF) gene.
J Med Genet 2003;40(1):45–50
Starr A, Michalewski HJ, Zeng FG, et al.
Pathology and physiology of auditory neuropathy
with a novel mutation in the MPZ gene (Tyr145> Ser). Brain 2003;126(Pt 7):1604–1619
Hood LJ, Wilensky D, Li L, Berlin CI. The role
of FM technology in the management of patients
with auditory neuropathy/dys-synchrony. In:
Fabry DA, De Conde Johnson C, eds. ACCESS:
Achieving, Clear Communication Employing
Sound Solutions–2003. Proceedings of the 1st
International FM Conference; 2004; Chicago, IL
Berlin CI, Li L, Hood LJ, Morlet T, Rose K,
Brashears S. Auditory neuropathy/dys-synchrony:
after the diagnosis, then what? Semin Hear 2002;
23:209–214
Trautwein PG, Sininger YS, Nelson R. Cochlear
implantation of auditory neuropathy. J Am Acad
Audiol 2000;11(6):309–315
Shallop JK, Peterson A, Facer GW, Fabry LB,
Driscoll CLW. Cochlear implants in five cases of
auditory neuropathy: postoperative findings and
progress. Laryngoscope 2001;111(4 Pt 1):555–
562
Peterson A, Shallop J, Driscoll C, et al. Outcomes
of cochlear implantation in children with auditory
neuropathy. J Am Acad Audiol 2003;14(4):
188–201
Zeng FG, Liu S. Speech perception in individuals
with auditory neuropathy. J Speech Lang Hear
Res 2006;49(2):367–380
Buchman CA, Roush PA, Teagle HF, Brown CJ,
Zdanski CJ, Grose JH. Auditory neuropathy
characteristics in children with cochlear nerve
deficiency. Ear Hear 2006;27(4):399–408
Walton J, Gibson WP, Sanli H, Prelog K.
Predicting cochlear implant outcomes in children
with auditory neuropathy. Otol Neurotol 2008;
29(3):302–309
Narne VK, Vanaja CS. Perception of envelopeenhanced speech in the presence of noise by
individuals with auditory neuropathy. Ear Hear
2009;30(1):136–142
121
Downloaded by: SASLHA. Copyrighted material.
VARIATION IN AUDITORY NEUROPATHY SPECTRUM DISORDER/HOOD
SEMINARS IN HEARING/VOLUME 32, NUMBER 2
2011
29. McMahon CM, Patuzzi RB, Gibson WP, Sanli
H. Frequency-specific electrocochleography indicates that presynaptic and postsynaptic mechanisms of auditory neuropathy exist. Ear Hear
2008;29(3):314–325
30. Santarelli R, Starr A, Michalewski HJ, Arslan E.
Neural and receptor cochlear potentials obtained
by transtympanic electrocochleography in auditory
neuropathy. Clin Neurophysiol 2008;119(5):
1028–1041
31. Michalewski HJ, Starr A, Nguyen TT, Kong YY,
Zeng FG. Auditory temporal processes in normalhearing individuals and in patients with auditory
neuropathy. Clin Neurophysiol 2005;116(3):669–
680
32. Rance G, Cone-Wesson B, Wunderlich J, Dowell
R. Speech perception and cortical event related
potentials in children with auditory neuropathy.
Ear Hear 2002;23(3):239–253
Downloaded by: SASLHA. Copyrighted material.
122