Auditory Neuropathy

Spectrum Disorder:
Hearing Development: An Overview
Variation in diagnostic information
and differential diagnosis

Introduction Inner Ear at Birth

ƒThe hearing function Left

Right ƒ Cochlea has its full size
appears around the 26th Auditory
cortex
Auditory

ƒ Inner Hair Cells (sensory

cortex
week of gestation and
functional development transducers) are present and
ends around 12+ years. Cochlea Medial geniculate nucleus
functioning
Inferior colliculus ƒ Outer Hair Cells (cochlear
amplifier) are present and
functioning
Auditory Superior
nerve fiber Olivary
Ipsilateral
Cochlear nucleus
nucleus

Cochlear Active Mechanisms Peripheral Afferent Auditory Pathways

Inferior
Colliculus

Lateral
Lemniscus

Cochlear Nuclei
Auditory Nerve
Superior Olive

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Peripheral Afferent Auditory Pathways Auditory Brainstem Responses: Latencies
ƒ ABR wave latencies are not mature at birth.

ƒ Afferent innervation of the cochlea starts around 11-12 ƒ Increase of nervous fiber synchronization,
weeks of gestation and myelination begins around 26 myelinization and synaptic efficiency will induce a
weeks. decrease in latency of ABR waves with age.

ƒ An adult latency is obtained at 5 weeks after birth for

ƒ Most studies of brainstem myelination suggest that the wave I.
degree of myelination at 1 year approximates that of the
adult state. Minor changes may occur after 1 year of age. ƒ The II-III interval does not reach an adult level until
between 1 and 2 years of age.

ƒ An adult latency for wave V is observed around 3 to 5

years of age.

ABR: Frequency ABR: Thresholds

ƒ Studies of the maturation of ABRs according to the
frequency of stimulation have shown several contradictory ƒ ABR thresholds at birth are elevated by to 10-25 dB relative to adult
results. thresholds.
ƒ They become adult-like around 12 months of age.
ƒ From a general point of view, there is a gradient of
development for cochlear frequency selectivity, from low to ƒ Threshold elevation is greatest for high-frequency stimuli.
high frequencies. The development lasts at least one year.

Development of Peripheral Afferent Central

Auditory Pathways Auditory Cortex
Nervous
ƒ In summary, anatomical and physiological data show that Thalamus System
the peripheral auditory system shows most of its mature
features around 1 year of age.
ƒ However, some tasks involving the periphery do not mature
until several years of age.
ƒ Maturation of ability to process complex sounds such as
speech not entirely known.

2
Central Nervous System
ƒ Myelination in the thalamocortical auditory radiations begins after the
40th week of gestation.

ƒ The development of the human auditory cortex continues well into the
early teen years.

ƒ The cytoarchitectural development is uniform across the superior

temporal lobe.

ƒ Studies of synaptic densities show an increase in densities during the

first year of life, a peak in synaptic densities between 2 and 4 years, and
a subsequent slow decrease in synaptic densities to approximately 50%
of the peak in adolescent brains.

From Moore and Guan, 2001

Auditory Late Responses

Middle Latency Responses
or Cortical Auditory Evoked Potentials
ƒ The middle latency responses arises from the upper
brainstem and primary auditory projection areas. ƒ ALRs are present in premature babies at a
time when cortical development is still very
ƒ As with ABRs, the MLR latencies decrease with age. immature and afferent fibers are only
beginning to be seen in the cortical plate.
Changes can be seen well into childhood, and adult
ƒ Latencies are relatively stable from birth to 6
characteristics are not reached until 10-12 years of age. years. Components P1 and N2 decreased in
amplitude, while component N1 and P2
increase in amplitude from birth to adulthood.
ƒ The general waveform morphology reaches
maturity around 12 years of age, although
latencies and amplitudes of the various
components continue to change beyond this
age.

From Tucker and Ruth, 1996 From Wunderlich and Cone-Wesson, 2006

Behavioral Testing: Absolute Thresholds Intensity Discrimination

ƒ The measure of auditory thresholds for pure tones in
infants 6 to 18 months old can be higher than in adults
by about 15 to 25 dB depending on the frequency of the
stimulus.
ƒ Hearing levels for pure tones improve with age up to 10
years.
ƒ From 6 to 12 month, intensity detection thresholds
improve from 6 to 4 dB. Further improvement to 2 dB
has been reported for preschoolers, but the value is still
not adult-like (less than 1 dB) until adolescence.

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 Temporal Resolution Efferent
Auditory
ƒ The ability to detect and discriminate rapid spectral Pathways
changes enables the detection of phonemes.
ƒ Gap detection tasks:
– 3- and 6- month-olds have gap detection thresholds 4-5 times
longer than adults.
– The gap detection threshold seems to be twice as long at 12
months of age as in adults.
– The gap detection threshold improves until at least 5 years
and perhaps up to 10 years.

Efferent Control of the Auditory Periphery

ƒ The MOCS in itself can be
considered completely
ƒ Olivocochlear reflex (OCR) myelinated after 2 years of age.
ƒ Cochlear function is modified ƒ A later time course is likely for
the other neural pathways
by efferent fibers of the coming from the cortex and
innervating the superior olivary
olivocochlear bundle (OCB) complex.
– Medial OCB fibers are directed to ƒ This suggests that some
changes may be recordable in
the outer hair cells. the MOCS up to the age of 10-
– Lateral OCB fibers synapse just 12 years.
under the inner hair cells on the
peripheral processes of afferent
neurons.

By the end of the second

trimester of gestation, the L R In early childhood, from the
L R
H H cochlea has acquired a H H sixth post-natal month to age
very adult-like five, there is progressive
configuration and is maturation of the thalamic
functioning. projections to the cortex.
IC IC IC IC
During the perinatal Later childhood, from six to
period, the brainstem twelve years, is the time of
reaches a mature state, maturation of the superficial
MOS MOS and brainstem activity is MOS MOS cortical layers and their
reflected in behavioral intracortical connections,
responses to sound, accompanied by improved
including phonetic linguistic discriminative
CN CN discrimination, and in CN CN abilities.
evoked brainstem and
early middle latency
LE Cochlea RE Cochlea responses. LE Cochlea RE Cochlea

speech in noise speech in noise speech in noise speech in noise

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Normal Development Communication
ƒ 0-4 months: Should startle to loud sounds, quiet to mother’s Communication and Language Age (months)
voice, momentarily cease activity when sound is presented at a
conversational level
Smiles in response to face, voice 1.5
ƒ 5-6 months: Should correctly localize to sound presented in a
horizontal plane, begin to imitate sounds in own speech repertoire Monosyllabic babble 6
or at least reciprocally vocalize with an adult. Inhibits to “no” 7
ƒ 7-12 months: Should correctly localize to sound presented in any
Follows 1-step command with gesture 7
plane, should respond to name, even when spoken quietly.
ƒ 13-15 months: Should point toward an unexpected sound or to Follows 1-step command without gesture 10
familiar objects or persons when asked. Speaks first real word 12
ƒ 16-18 months: Should follow simple directions without gesture or
Speaks 4-6 words 15
other visual cues; can be trained to reach toward an interesting
toy at midline when a sound is presented. Speaks 10-15 words 18
ƒ 19-24 months: Should point to body parts when asked; by 21 Speaks 2-word sentence 19
months, can be trained to perform play audiometry.

Matkin, 1984

Abnormal Speech Development

Age (months)

12 No differentiated babbling or vocal imitation

18 No use of single words Auditory Neuropathy Spectrum

24 Single-word vocabulary of <10 words Disorder
30 Fewer than 100 words; no evidence of 2-word combinations;
unintelligible
Characteristics
36 Fewer than 200 words; no use of telegraphic sentences; clarity
<50%

48 Fewer than 600 words; no use of single sentences; clarity <80%

Matkin, 1984

Age at onset Varieties of ANSD

ƒ Majority of subjects present with ANSD symptoms
in infancy.
ƒ Some subjects develop the ANSD condition in
adolescence or early adulthood.
– If diagnosis based on OAE, this second category is
certainly underestimated since some affected patients
lose their OAEs with time.
ƒ 50% of patients have no defined etiology
ƒ Genetic factors: 40%
ƒ Toxic-metabolic (anoxia, hyperbilirubinemia),
immunological (drug reaction, demyelination),
infectious disease (post viral): 10%
ƒ Rare cases of head injury (children and adults)
ƒ Some forms of ANSD may be progressive
ƒ Some forms of ANSD may also involve OHC
functions

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Patients vary in demonstration of ANSD Kresge Database:
other peripheral neuropathies. Ears Affected

– Up to 40% of patients with ANSD show a peripheral

ƒ Bilateral: 92.9%
neuropathy. Symptom onset usually occurs later in life, after
the age of 15. ƒ Unilateral: 7.1%
– Some patients have less apparent neuropathy which is only
evident on clinical examination.
– Other patients demonstrate no signs of neuropathy and have
only abnormal auditory findings. Bilateral
Unilateral
– Late onset ANSD

126 Patients with ANSD Neonatal Causes

ƒ Several risk factors have been associated with

80 ANSD
61.9%
70 ƒ The current list of risk factors includes: history of
60 prematurity, low birth weight, hyperbilirubinemia,
50 anoxia, hypoxia, previous meningitis, ototoxic
40
25.4% drug exposure, cerebral palsy, intracranial
30 hemorrhage, sepsis, traumatic brain injury,
20
12.7% ischemia, central nervous system immaturity, and
10 infection (mumps) alone or in combination.
0
Bilateral ANSD Unilateral ANSD Unilateral
ANSD/SNHL
Atypical

Genetic Causes Otoferlin

ƒ Siblings or other family members with auditory neuropathy
suggests genetic causes for some forms.
ƒ Many different genetic and non-genetic causes
ƒ May be syndromic or non-syndromic
ƒ Dominant, recessive, mitochondrial and X-linked patterns of
inheritance are found
Non-syndromic recessive ANSD
ƒ Otoferlin is expressed in IHCs, possible roles in membrane trafficking
and/or IHC synaptic vesicle fusion
ƒ Otoferlin plays a crucial role in vesicle release at the synapse between
IHCs and auditory nerve fibers. When the OTOF gene is mutated, the
neurotransmitter release is adversely affected which results in absent
ABRs consistent with a functional loss of auditory nerve input.
ƒ At least 42 pathogenic mutations of OTOF have been identified so far,
all resulting in a homogeneous phenotype of pre-lingual profound
hearing loss
ƒ Hearing loss is severe to profound and speech comprehension is a
major impairment

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Pejvakin
Mutation in the Pejvakin gene causes nonsyndromic, prelingual,
severe to profound sensorineural hearing impairment, which
fits the diagnostic criteria for ANSD.
The mutation induces dysfunction in neurons along the auditory
pathway, which is consistent with the observed distribution of
pejvakin in the cell bodies of neurons in the spiral ganglion
and the brainstem auditory nuclei.
Friedreich Ataxia
ƒ Some patients, notably among those with more
severe neurological symptoms, complain about
auditory difficulties or decreased intelligibility in
noise. ABR can be abnormal or absent in these
patients.
ƒ ABR abnormalities appear to be more important in
patients with early onset of the disorder and
abnormalities progress with the severity of the
disease, until the response is totally absent.
Leber’s Hereditary Optic Neuropathy
ƒ Two reports describe progressive ANSD in
patients with Leber’s hereditary optic neuropathy
Charcot-Marie-Tooth
ƒ Hearing loss has been found in the primary demyelinating form
CMT1 due to mutation of PMP22 gene duplication, in the primary
axonal forms (CMT2) due to mutations of MPZ gene, connexin 31
(GJB3) gene, connexin 32 (Cx32) gene, in a mixed
demyelinating/axonal autosomal recessive motor-sensory
neuropathy, particular to Roma populations due to a mutation of
the NDRG1 gene and in the X-linked dominant disease (CMTX)
caused by a point mutation in the gap junction protein connexin-
32 gene on the X chromosome which is expressed in Schwann
cells and oligodendrocytes.
ƒ Several studies showed that hearing loss in CMT can be
attributed to an accompanying neuropathy of the auditory nerve
sparing the IHCs.
Waardenburg Syndrome
ƒ ANSD has been reported in 2 siblings with
Waardenburg Type 2 syndrome
Mohr-Tranebjærg syndrome
ƒ Hearing loss in this disorder is likely to be the
result of a postnatal and progressive degeneration
of cochlear neurons and probably constitutes a
true auditory neuropathy.
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Autosomal dominant optic atrophy Other candidates

ƒ Autosomal dominant optic atrophy is a retinal
neuronal degenerative disease characterized by a
progressive bilateral visual loss and is associated
with SNHL that mimics ANSD with preserved
OAEs and absent or abnormal ABRs.
ƒ Hearing loss accompanying a mutation found in
the OPA1 gene suggests altered function of
terminal unmyelinated portions of auditory nerve
ƒ Cx 29 is now one of the candidates among other
genetic mutations that could explain
demyelination in the peripheral auditory system.
Cx29 is strongly and exclusively expressed in the
Schwann cells myelinating the auditory nerve
within the cochlea.
ƒ Misexpression of Pou3f1 results in peripheral
nerve hypomelination and axonal loss
ƒ A gene responsible for autosomal dominant
auditory neuropathy (AUNA1) has recently been
discovered.

Inner ear malformation Immunological Causes

ƒ Several cases of ANSD in children who present ƒ Guillain-Barre syndrome is an inflammatory

with enlarged vestibular aqueduct (EVA) have demyelinating polyneuropathy, an autoimmune
been reported disorder affecting the peripheral nervous system,
usually triggered by an acute infectious process
and can cause ANSD.

Miscellaneous Causes History and Risk Factors (153 pediatric patients)

Number Percent
ƒ Other factors leading to ANSD have been Normal history 28 18.3
mentioned in the literature, such as case reports Normal pregnancy 31 20.3
of newborns and children with ANSD presumably Premature birth 73 47.7
caused by a cerebellopontine angle arachnoid Hyperbilirubinemia 74 48.4
cyst. Exchange transfusion 31 20.3
Anoxia 26 17
ƒ Not all risk factors have been confirmed as a direct Respiratory distress 23 15
cause of ANSD. Artificial ventilation 35 22.9
Ototoxic drugs 44 28.8
Low birth weight 11 7.2
Anemia 6 3.9

Berlin, Hood, Morlet et al., 2010

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 Auditory Neuropathy Spectrum
Disorder Test Battery
Test Battery following the Diagnosis ƒ Genetic Evaluation

Test Battery Imaging studies

ƒ Genetic Evaluation ƒ Imaging studies are useful in evaluating hearing
ƒ Imaging Studies loss to diagnose inner ear malformations as well
as to check for presence and size of the auditory
nerve.
ƒ Absent or hypoplastic auditory nerves are not
uncommon (Buchman et al., 2006) and these cases
usually resemble ANSD when OHC are present
and functioning.
ƒ Audiological management in these patients is
problematic because a cochlear implant cannot
work when the nerve is absent and might not work
well when the nerve is hypoplastic

Absent or hypoplastic auditory nerves are not uncommon and 32 Unilateral ANSD
these cases usually resemble ANSD when OHC are present and
functioning.

100%
90%
80%
70% others
60% 19
50% Absent/Hypoplastic
Nerve
40%
30% 13
20%
10%
0%
Unilateral ANSD

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ABR at 1 year Klippel-Feil Syndrome: Imaging report at 5 years

ƒ The left internal auditory canal is narrowed. There

is severe hypoplasia/aplasia of the left cochlea.
ƒ The left cochlear nerve is absent. The left facial
nerve and the vestibular nerves appear normal.
The left vestibule and semicircular canals are
normal.
ƒ The right internal auditory canal and inner ear
structures are within normal limits.

Audiogram at 5 years

EVA: Definition
ƒ Enlarged vestibular aqueduct (EVA) is the most common radiological
Enlarged vestibular aqueduct abnormality seen in children with sensorineural hearing loss (SNHL).
EVA can be associated with other congenital ear anomalies, such as
a hypoplastic cochlea.
ƒ SNHL onset may occur from birth to adolescence, usually during
childhood and may be precipitated by various factors such as head
trauma. Hearing loss is often progressive and can fluctuate.
ƒ Vestibular and balance disorders can also be associated.
ƒ Children with an EVA present with a wide variety of audiometric
thresholds and physiologic measurements.
ƒ The diagnosis of EVA is usually realized after the SNHL and/or
vestibular disorder is diagnosed by radiologic assessment, but can
sometimes be realized incidentally in children with no hearing or
vestibular symptoms yet who receive an imaging study for an
unrelated reason.

10
EVA EVA
ƒ Studies suggest that most children with EVA will develop
ƒ EVA has many causes, not all of which are fully understood.
some degree of hearing loss.
The most well-known cause of EVA and hearing loss is
ƒ Five to fifteen percent of children with SNHL, or hearing loss mutations to a gene known as SLC26A4 (also referred to as
caused by damage to cochlear sensory cells, have EVA. the PDS gene) on chromosome 7. Other unknown genetic or
However, it is not clear if EVA causes the hearing loss in environmental factors also may result in EVA.
every case.
ƒ Head trauma is one environmental factor that is believed to
ƒ In addition to causing hearing loss, EVA may affect balance.
precipitate progression of hearing loss associated with EVA.
However, the brain is very good at making up for a weak
vestibular system, and most children and adults with EVA
do not have a problem with their balance or have difficulty
doing routine tasks.

Bilateral EVA
Audiometric Pattern in 17/33 patients
125 250 500 1 2 4 8

ƒ Agreement between EVA side and HL 0

[ R ]
10 [ L [ R ]
] L L R
L
20 R L
L R [ R
ƒ Agreement between different audiological tests: 30 L
40 L ]
– OAEs 50
– ABRs 60

– MEMRs 70
80 Normal MEMRs
– PTA
90
– Speech 100

110
120

Subject 037 Subject 006

Audiometric Pattern in 3/33 patients Bilateral EVA

ƒ Agreement between EVA side and HL

ƒ Some disagreement between tests:

– OAEs
– ABRs Normal MEMR
– MEMRs LE & RE
– PTA
– Speech

Subject 029

11
 Normal MEMR RE LE EVA
Absent MEMR LE
125 250 500 1 2 4 8

0
R R R R R
10 R
L1
20 L1
L1
30 L1 L1
40 L2
L3
L3
L2
L2
L1 Bilateral EVA, Unilateral HL 3/33
50 L3 L2
L3
60 L2 L3
L3 L2
70
80

90
100

110
120
Subject 021

21

Bilateral EVA, Unilateral HL Bilateral EVA, Unilateral HL

125 250 500 1 2 4 8 125 250 500 1 2 4 8

0 0

10 L 10
L L R R
20 L L L 20
R
30 L 30 R
40 40

Normal MEMR
50 R 50

LE 60 60 L
L
Absent MEMR 70 R 70
RE 80
R 80

90 R 90
100 R R R R 100 L
L
110 110
120 120

Subject 022 Subject 013

LE EVA

Unilateral EVA and Bilateral HL 3/33

Subject 015 Absent MEMRs Subject 030

and OAEs bilaterally

12
 ANSD Pattern LE EVA

Auditory Neuropathy Spectrum

Disorder (ANSD) Pattern (7/33 patients)

Subject 004

ANSD Pattern RE EVA

Subject 035

Present CM, Absent ABR

ANSD Pattern LE EVA

Present CM, Absent ABR RE

Subject 037

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EVA Auditory Processing Disorders

ƒ Phenotypic expressions associated with EVA are

heterogeneous to include the following possibilities:
– normal hearing
– total deafness
– progressive sensorineural hearing loss
– fluctuating sensorineural hearing loss or sudden
sensorineural hearing loss, sometimes subsequent to head
trauma.
– There is not always agreement between OAEs, ABRs,
MEMRs, PTA & speech scores.

APD suspected ANSD vs APD

ANSD APD

Tympanogram Normal Normal

MEMR Abnormal or absent Present
OAE Present or absent (over Present
time)
ABR Abnormal or absent Normal
Pure-tone thresholds Normal to Normal
severe/profound
Word recognition (quiet) Excellent to poor Excellent
Word recognition (noise) Poor Fair to poor

Test Battery Test Battery

ƒ Imaging Studies ƒ Imaging Studies
ƒ Genetic Evaluation ƒ Genetic Evaluation
ƒ Ophthalmology: ƒ Ophthalmology
– Children with non-syndromic SNHL have an ƒ Speech/Language Evaluation
approximately three to fourfold increase in ocular
abnormalities compared with the general pediatric
population.

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Test Battery Test Battery
ƒ Imaging Studies ƒ Imaging Studies
ƒ Genetic Evaluation ƒ Genetic Evaluation
ƒ Ophthalmology ƒ Ophthalmology
ƒ Speech/Language Evaluation ƒ Speech/Language Evaluation
ƒ Neurology ƒ Neurology
ƒ Vestibular and Balance testing

Dizziness in Children Vestibular and Balance Disorders

ƒ Difficult to diagnose as ƒ The general prevalence of pediatric vestibular
children may:
dysfunction is estimated at between 8% and
– Not be able to describe the
symptoms 18%.
– Be thought of as being clumsy
ƒ Sensorineural hearing loss is reported to be
– Be considered having
behavioral problems associated with vestibular dysfunction in 20%-
– Not complain! 70% of cases.
ƒ Children with abnormal vestibular
ƒ Vestibular Evoked Myogenic Potentials (VEMP)
function can compensate in many may be useful in case of ANSD (could help
ways. diagnose vestibular neuropathy)

Concurrent Neuropathies VEMPs in patients w/ANSD

SUBJECTS VEMP Abnormal
ƒ In children with ANSD, the search for other related
62 VEMPS
neuropathies is a critical component of the clinical
evaluation to plan rehabilitation as it has been estimated A. I. duPont Hospital
Ongoing Study
26 patients,
Ages-16 mo. to 14 yrs.
8 of 45 ears 18%
1 ear- CNT
that 1/3 of patients with ANSD may present with other Morlet,T., O’Reilly, R. (6 w/ unil. ANSD)
neuropathies in the body. Sazgar, A.A., 8 patients 14 of 16 ears 87.5%
ƒ True vestibular neuropathies appear to coexist with ANSD Yazdani, N., 2010
Kaga & Starr, 2009
Ages 21-45 yrs.
8 patients, Absent VEMP
in some patients with concomitant peripheral neuropathies. Ages 16-72 yrs.
62.5%
(5 of 8 subjects)
Although no balance defect has been observed as yet in
Akdogan et al, 2008 3 patients, 3 of 6 ears
children with OTOF mutations, Dulon et al. (2009) showed Ages 4-5 yrs.
50%
that OTOF is critical for a highly sensitive and linear Sheykholeslami, et al, 1 patient 1 of 2 ears
calcium-dependent exocytosis at the vestibular hair cell 2005 Age 21 yrs.
50%
ribbon synapses. This suggests that some type of balance Sheykholeslami, et al, 3 patients, 6 of 6 ears 100%
dysfunction might appear in these children. 2000 Ages 57-71 yrs.
Wu, ZM, 2004 13 patients, 14 of 26 ears
Chinese Lang. article Age unspecified
54%
Fujikawa & Starr, 2000 14 patients, ages 14-75 9 of 14 w/ ABN calorics
yrs.

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 Vestibular Disorders and ANSD Friedreich Ataxia
ƒ Vestibular disorders and ANSD co-exist.
ƒ Vestibular Pathology often present both with and without
symptoms and/or complaints.
ƒ No clear patterns regarding ANSD & Vestibular dysfunction
have yet emerged likely due to limited data and the
heterogeneous nature of the ANSD diagnosis.
ƒ More research is needed.
ƒ Vestibular and Balance screening should become routine in
the work-up of all patients with Auditory Dysfunction
including ANSD.
ƒ Treatment & Rehabilitation possible

FA #5 – 30 years FA #1 – 25 years

250 Hz 500 Hz 1 kHz 2 kHz 4 kHz 8 kHz 250 Hz 500 Hz 1 kHz 2 kHz 4 kHz 8 kHz
10 10 10 5 10 5 10 5 0 5 5 0

FA #1 – 25 years FA #2 – 66 years

250 Hz 500 Hz 1 kHz 2 kHz 4 kHz 8 kHz 250 Hz 500 Hz 1 kHz 2 kHz 4 kHz 8 kHz
10 5 0 0 0 10 20 15 10 15 20 45

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 FA #4 – 13 years FA #4 – 13 years

Absent MEMR
Absent MEMR

250 Hz 500 Hz 1 kHz 2 kHz 4 kHz 8 kHz 250 Hz 500 Hz 1 kHz 2 kHz 4 kHz 8 kHz
25 20 5 15 15 15 25 20 15 10 15 30

Rance et al., 2010

What is the incidence of ANSD?

Auditory Neuropathy
Spectrum Disorder: ƒ At least 1 in 10 patients with sensorineural loss have
desynchronized ABRs, normal OAEs and/or large cochlear
microphonics.
Implications for Newborn Hearing
Screening

17
Goal: Screen all types of Hearing Loss
Inner Hair Cells (IHC) IHCs OK INNER HAIR CELLS
MISSING
SEND NEURAL PULSES TO THE BRAIN
(a) NORMAL (b) SENSITIVITY(c) CLARITY
HEARING LOSS
Harrison RV. An animal model of auditory neuropathy.
Ear & Hearing. 19(5):355-61, 1998 Oct
Special thanks to Mead
Killion, Ph.D.
MEMR
ƒ Absent or elevated in ANSD
ƒ Absence or elevated MEMR thresholds should
prompt for an ABR.
ƒ Recent study suggest that the MEMR test holds
promise as a useful diagnostic/screening
instrument in neonates (Mazlan et al., 2009).
ABR
ƒ Use of insert earphones: allow to distinguish the
CM from the electrical artifact generated by the
transducer
ƒ The ABR is markedly abnormal in individuals with
ANSD. Recordings might appear as
– 1) a “flat” ABR with no evidence of any peaks or
– 2) some poorly synchronized but evident later peaks
(wave V) that appear only to stimuli at elevated
stimulus levels.
Goal: Screen all types of Hearing Loss
Outer hair cells
Inner hair cells
Auditory
LOSS nerve
INSERM, Montpelier
Promenade ‘round the cochlea
OAEs in ANSD
ƒ OAEs are usually normal or near normal in individuals with
ANSD.
ƒ 4 main categories of patients based on OAE recording:
– Patients with normal OEAs. Their OAEs evolve with time as
OAEs in normal subjects.
– Patients with no OAEs from birth or soon thereafter (ototoxic
drugs (antibiotics, chemotherapy)
– Patients with temporary absent OAEs (conductive issue: ear
canal, middle ear).
– Patients whose OAEs (normal at birth) disappear with time.
Disappearance is sometimes due to hearing aid use or other
external factors. In some cases, disappearance of OAEs can
not be linked to an external factor and is probably due to
ANSD.
Cochlear Microphonic
ƒ Cochlear microphonic provides a valid measure of hair cell
function.
ƒ CM generally remain present in individuals with ANSD
despite loss of OAEs.
ƒ Appropriate identification of the CM will help in evaluating
outer hair cell function in patients who have lost or never
had OAEs and it will help evaluate outer hair cell function in
cases of middle ear effusion when the recording of OAEs is
not possible.
ƒ CM can become attenuated and difficult to detect when
patients are over the age of 50 years.
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Joint Committee on Infant Hearing Absence of Risk Factors in ANSD
ƒ What Are the Implications for Newborn Hearing Screening?
ƒ JCIH 2007 Statement: “The definition has been expanded … to
include neural hearing loss (eg, “auditory neuropathy / dys- Some infants with ANSD have no risk factors and
synchrony”) in infants admitted to the neonatal intensive care unit
(NICU)
come through the well-baby nursery.
ƒ Separate protocols are recommended for NICU and wellbaby NOT ALL infants with ANSD are found in the NICU
nurseries. NICU babies admitted for greater than 5 days are to
have auditory brainstem response (ABR) included as part of their
screening so that neural hearing loss will not be missed.”

Protocols for Screening in Premature

ANSD and Newborn Hearing Screening
Babies and Full-term Babies
ƒ If only OAEs are used as an initial screener, 10% of children
with HL who have normal OAEs also may have serious ƒ Percentage of preterms with ANSD is higher than
auditory synchrony problems. in fullterm babies.
ƒ Similarly, if only alternating polarity or single polarity ABR is
used as an initial screener, approximately 10% of children with ƒ Number of ANSD patients may end up being
flat or abnormal ABRs will have normal OAEs and may similar in both nurseries.
misdiagnosed.
ƒ Children with ANSD are currently being found more frequently ƒ Why would a different standard applied
because of the proliferation of newborn ABR-based hearing to identification of sensory hearing loss
screening programs.
(all nurseries) and ANSD (NICU only)?

Childhood Hearing Loss Age at onset in ANSD

ƒ Congenital ƒ Majority of subjects present with ANSD symptoms

– May be identified by universal newborn hearing in infancy.
screening ƒ Some subjects develop the ANSD condition in
ƒ Acquired/Late Onset adolescence or early adulthood.
ƒ Progressive – If diagnosis based on OAE, this second category is
certainly underestimated since some affected patients
– Child may have normal hearing at birth lose their OAEs with time.
– Loss of hearing over months or years
– Usually missed by universal newborn hearing
screening

19
20