auditory neuropathy spectrum Flashcards
what is ANDS
“Hearing disorder characterized by disruption of temporal coding of acoustic signals in auditory nerve fibers resulting in impairment of auditory perceptions relying on temporal cues”
-there is a disruption of neural synchrony
what is preserved with ANDS and what is affected
-pre-neural or cochlear OHC activity is preserved
>Frequency resolution is generally unaffected
>But the disordered auditory nerve function affects processing of auditory temporal cues causing disruption of temporal resolution and neural timing, leading to
>Interference with language comprehension, especially in noise
Localization of sound sources and binaural perception
what is not affected in ANSD
OHC are not affected
-the site of lesion is the synapse of the IHC to the nerve or the actual nerve
how can we notice if ANSD is present ?
1)Intact otoacoustic emissions (OAEs) but an absent or markedly abnormal ABR response
>OAEs are present because OAEs are related to OHC function and OHCs are intact in ANSD
»Although OAEs may disappear in later stages of the disease
The cochlear microphonic (CM) is present (sometimes even if OAEs are absent) because CM also shows activity from the OHCs
2)The ABR is abnormal/absent because the ABR is generated by neural structures, which are disrupted
>Neural integrity of the eighth nerve and lower brainstem pathways are affected in ANSD
**ECochG and ARTs also are absent because of VIII N involvement*
what are some controversy/gaps in knowledge in ANSD
-Nosology/Terminology
-Site of lesion
-Etiology
-Management
what is cochlear synaptopathy ?
-Cochlear synaptopathy, due to noise exposure or other causes, is the loss of the synchrony of neural firing causing loss of temporal resolution
-because of that, speech perception is also affected, because it’s hard to decode the signal esoecoially in noise
-Subsequent gradual neural degeneration adversely affects fine speech structure decoding and hence speech perception, especially in noise, which also is seen in ANSD
ANSD can be a result from ?
1)damage to the synaptic junction of IHC
2)Neurotrasmitters aren’t firing in a normal order by the synapses of the inner HC
3)-spiral ganglion is injured
4)audiotry nerve is absent
5)Demylination of axons (look at this one)
-Selective loss/damage of synaptic junctions of IHCs
-Disordered release of neurotransmitters by IHC synapses
Injury to the spiral ganglion
-Demyelination/damage to myelin sheath, cell body, or axon of CN VIII, which can spread to portions of the brainstem
-Auditory nerve hypoplasia/absence
ohc help in what?
improve sound detection
inner hair cells are important for ?
critical for sound discrimination
ribbon synapse help in ?
They help with encoding sound with temporal precision
-Ribbon synapses (vesicles that contain neurotransmitters) of the IHCs are highly specialized for encoding sound with sub-millisecond temporal precision
>Ribbon synapses are mediated by calcium channels
what is another name for ANSD?
cochlear synaptopathy or hidden hl
what protein is coding otoferlin ?
DFNB9 is autosomal recessive deafness resulting from mutations of OTOF gene encoding the protein otoferlin
what is otoferlin ?
Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory IHC ribbon synapses
ANDS can be what?
ANSD can be idiopathic, genetic, or environmental
can ANDS be syndromic or non syndromic ?
both
what is the mode of inheritance for ANSD ?
in NONsyndromic, the mode of transmission is recessive
>an ample of this is mutations of Connexin 26 and Otoferlin (DFNB9)
what is Otoferlin (DFNB9
OTOF gene involved in synthesis of otoferlin localized to IHC and often associated with synapsis of IHC to VIII nerve fibers
what is syndromic ANSD associated with
Often associated with peripheral neuropathies such as
> charcot- marie tooth
Fredrich ataxia
can mitochondrial mode of inheritance affect ANDs?
yes
can immune disorders be associated with ANSD
yes, they can be accompanied by deafness because of ANSD
an ex of this would be:
>Guillian-Barre syndrome:
»»Affects proximal nerve roots and proximal portions of VIII N
»»>Deafness and paralysis with a lengthy recovery period
what metabolic disorders might be associated with ANSD?
diabetic neuropathy, typically acquired in adults
-can have issues with WRS
how might environment affect ANSD ?
-viral infections can cause problems
an ex mumps and measles (can cause as unilateral ANSD)
what would happen if the arterial supply is compromised in ANSD?
-then neural and cochlear receptors are disrupted
-In any condition, if arterial supply of the cochlea is compromised then OHCs are affected and OAEs maybe absent along with the ABR, confusing the clinical picture of ANSD
what would happen in the arterial supply is not affected in ANSD?
If the arterial supply is not affected then OAEs, CM, and sometimes the wave 1 of the ABR can be identified
what are primary risks of ANSD?
1)Prematurity and very low birth weight
»»spontaneous improvement may occur w/in 2 years of life
2)Prolonged stay in the NICU
3)Anoxia/hypoxia and accompanying metabolic acidosis
4)Seizures
5)hyperbilirubinemia
what is hyperbilirubinemia ?
jaundice
can hyperbilirbium and ANSD be recovered?
yes, so no more jaundice
what is the site of ANSD with hyperbilirb and ANSD
-site of lesion is not the VIII N
»>The damage begins in the CANS and the brainstem, primarily the cochlear nuclei, and then descends to the VIII N
»>Bilirubin deposits in the auditory brainstem & VIII nerve ganglion cells
»>Nerve death or dysfunction will ensue but the IHCs are unaffected
-it’s affecting the CNS and then goes to the 8th nerve
what is the recovery time for ANSD with hyperbuili?
w/in 2 years, but we’re not sure if neural synchrony at the brainstem level is restored in normal auditory processing
-we’re also not sure what their staus of ABR will be so we have to wait 2 years
How do we diagnose ANSD
1)Careful case history
2)OAEs
3)ABR
*****combined use of OAEs and ABRS w/ 2 polarities is essential
4)Middle ear acoustic reflexes (abnormal/absent)
5)Behavioral assessment
6)Speech audiometry
7)Electrocochleography (ECochG)
»>abnormal
8)Vestibular assessment (some may present as “clumsy”)
9)Functional assessment for young children (questionnaires)
How are OAES in ANSD?
present, at least during early years of life
how does contralateral OAE suppression look like in ANSD?
-It is a normal phenomenon that shows a decrease in OAE amplitude with masking to the contralateral ear
»>OAE suppression is mediated through the medial olivo-cochlear bundle via the efferent auditory pathways
»>Involvement of efferent VIII N fibers prevents neural impulses from reaching OHCs, i.e.,
* no OAE suppression- abnormal*
take away message: you want to see contralateral OAE compression but if you don’t then that’s not normal, you want to see OAE compression
how does ABR look like in ANSD?
absent
because it’s absent there are no measurable aspects of the ABR none of the typical diagnostic measures of an ABR can be carried out
»»>But a cochlear microphonic (CM) should be present
-you won’t see amplitude or latency of waves 1, 3, 5
how are ABR drawn on a graph for ANSD
1) you will see a CM
>It occurs ~1 ms after stimulus presentation and follows the phase of the stimulus, occurring before wave I of the ABR
>CM shows a downward shift from baseline with a rarefaction click stimulus and an upward shift with a condensation click stimulus
»> CM follows the signal, thats why it does this
how might ABRs look like with neuropathies
In patients with neuropathies without an ABR, CM may be larger
how might ABRs look like in infants
In infants, the CM may even continue over several milliseconds (4 to 6 ms) that simulates an ABR response but is artefactual
how might amplitude be affected in ABR ?
-All ABR waves increase in latency and decrease in amplitude as stimulus intensity decreases
»>In contrast, the CM does NOT increase in latency as the stimulus intensity decreases
»>Comparison of response latency at various intensities can be used to distinguish cochlear (CM) from neural (ABR) responses
what is something important to remember in ANSD with ABRs
ABRs with no CM in ANSD are generally a result of either instrumental or clinician error or use of an alternating polarity
look at slide 26
how do we diagnose ANSD with using an ABR?
1) use a click evoked ABR
»click as your stim
2)Performed at high level click stimulus (75 to 90 dB nHL) using rarefaction and condensation polarity in separate trials
3)If there is no reversal of the waveform with reversal of polarity, it confirms a true auditory nerve response
4)If only one stimulus polarity is used and the latency of waves does not increase with a decrease in stimulus intensity, the response is probably CM; suspect ANSD
5)Once an ANSD pattern (CM reversal) is identified, an ABR cannot be used to estimate an infant’s hearing thresholds
what is something important to remember in during measuing an ABR with ANSD?
Once an ANSD pattern (CM reversal) is identified, an ABR cannot be used to estimate an infant’s hearing thresholds
can we use an alternating polarity for ABR to diagnose ANSD?
no!
An alternating polarity should not be used in suspected cases of ANSD because it is a sum of condensation and rarefaction polarities and, therefore, will not show response reversal
are behavioral assessments important for ANSD?
yes they are because ABRS can’t be preformed for infants w/ ANSD
how might hearing appear like in ANSD
-normal/mild to a severe to profound SNHL with varying configurations
>It can be unilateral or bilateral
>~ 30 to 40% show a rising configuration hearing loss
>threshold fluctations
-keep in mind that fluctuations in hearing thresholds also are reported
how does speech audiometry look like in ANSD?
-speech perception is impacted
-remember they will have normal puretone thresholds because IHC and CN 8 nerve
-speech in noise is the give away
*Speech-in-noise testing is highly recommended when developmentally appropriate
**
how might reflexes look like in ANSD
-Abnormal reflex thresholds with ANSD even with normal/mild SNHL
»>Because of auditory nerve/synapse involvement the afferent reflex arc is affected
if the 8th nerve is is damaged, how will you expect your testing to appear to look like ?
ANY and ALL test that involve the 8th nerve will come out as abnormal because the 8th nerve is damages (that’s the site of lession
look at the picture on slide 35
what are some assessments recommended for ANSD ?
-Assessments recommended for ANSD are similar to those for children with SNHL including behavioral & physiologic measures
Such as:
>Pediatric development evaluation and history
>Otologic evaluation with imaging of cochlea & auditory nerve
»»Majority of children with ANSD may have additional intra-cranial anomalies, including
»»»»>Abnormal VIII N, abnormalities of brainstem, cerebellum, midbrain, CSF, ventricles, and vascular malformations
>Vestibular assessment if otologic evaluation/history warrants it
>Genetic evaluation
>Ophthalmologic assessment (if associated with peripheral neuropathies)
>Neurologic evaluation to assess peripheral and cranial nerve function including conductional velocity studies and imaging
>Communication assessment
how can we manage ANSD?
1) h.a and FM but there’s limited benefit
2) we can continue have them use auditory and visual stimulation
3) change their communication to manual communication (like cued speech or ASL)
-CI are the BEST form of treatment, it doesn’t matter what their audiometric thresholds are
-gene therapy
ANSD is a question of how severe what is
how severe is is the dys-synchrony, NOT how severe the HL is
when are CIs successful?
1) defects in the synapse
2) or biochemical abnormality of neurotransmitter substances
what is the gene involved with ANSD?
autosomal recessive deafness, DFNB9, caused by mutations of the OTOF (otoferlin) gene
-hair cells and cn 8 fibers are fine
-they inject the virus into the cochlea and wait to see if it works and it does
> nothing too crazy happened tho
what did ANSD show us ?
shows us that sound audibility and auditory “perception” are not the same thing
when are CIs not successful??
1)when there’s a loss of myelin
2) or a loss of neural elements, including the cn 8
What is a summary of results we might see in ANSD
1) present OAEs
2) Absent ABR
>you see a cochlear microphonic
>use a 2 polarity click stimulus at 70 to 90 dB nHL
3) abnormal reflexes
4) Terrible WRS in noise
5)audiogram can be anything because it doesn’t measure neural dys-synchrony
do all patients benefit from amplification with ANSD?
no
some benefit with amplification
some benefit from CI
some don’t benefit from either
