ANSD

ANSD definition

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

ANSD is a disruption of

neural synchrony

with ANSD, pre-neural or cochlear OHC activity is

normal

frequency resolution is _______ by ANSD

unaffected

ANSD affects the ______ of temporal cues causing disruption of temporal resolution and neural timing

processing

ANSD interferes with ______ comprehension, especially in noise

language

ANSD also impacts

localization of sound sources and binaural perception

with ANSD, OAEs and/or cochlear microphonic are

intact

ABR is _____ with ANSD

abnormal

what other two tests are absent with ANSD because of VIII N involvement

ECochG and ARTs

potential ANSD sites of lesion

- selective loss/damage of synaptic junctions of IHCs

- disordered release of neurotransmitters by IHC synapses

- injury to the spiral ganglion

- demeyelination/damage to myelin sheath, cell body, or axon of CN VIII

- auditory nerve hypoplasia/absense

ANSD operational definition

normal OAEs, abnormal ABR

outer hair cells improve sound detection, but inner hair cells are critical for

sound discrimination

ribbon synapses

vesicles that contain neurotransmitters

ribbon synapses of IHCs are highly specialized for

encoding sound with sub-millisecond temporal precision

ribbon synapses are mediated by

calcium channels

DFNB9 is

autosomal recessive deafness resulting from a nonsense mutation of the OTOF gene

what does the OTOF gene encode for

the protein otoferlin

otoferlin acts as a

Ca2+ sensor for vesicle fusion and vesicle pool replenishment at IHC ribbon synapses

mutant mice that lack otoferlin are

profoundly deaf due to failure of sound-evoked neurotransmitter release

gene therapy clinical trials are underway to try to restore the

OTOF gene in the cochlea

incidence of ANSD

~10-15% of the deaf population

1 in 300 well babies

higher number in NICU babies

~60% of individuals with ANSD have other disabilities such as

cognitive, vision, motor, etc.

current estimates of ANSD prevalence in children with permanent hearing loss is

~7 to 10%

etiology of ANSD can be

idiopathic

genetic

environmental

genetic based ANSD non-syndromic inheritance pattern is

autosomal recessive

non-syndromic genetic based ANSD examples

mutations of Connexin 26 and Oterferlin (DFNB9)

genetic based syndromic ANSD is often associated with

peripheral neuropathies

peripheral neuropathies associated with genetic based syndromic ANSD

charcot-marie-tooth

friedreich's ataxia

metabolic disorder that is associated with ANSD

diabetic neuropathy, typically acquired in adults

immune disorder that can be accompanied by ANSD

guillan-barre syndrome

environmental based ANSD

viral infections such as mumps and measles

prolonged stay in the NICU is a risk factor for ANSD possibly because of

serious and complicated medical issues

and/or

low birth weight and prematurity

if in any condition the arterial supply of the cochlea is compromised then

OHCs are affected and the OAEs may be absent along with ABR

ANSD risk factors

prematurity and very low birth weight

anoxia/hypoxia and accompanying metabolic acidosis

seizures

hyperbilirubinemia (jaundice)

ANSD due to prematurity and very low birth weight can be

transient and spontaneous improvement may occur within 2 years of life

ANSD from anoxia/hypoxia and accompanying metabolic acidosis is due to

damage to the cochlear hair cells, especially the IHCs, the synapses, and the nerve itself due to oxygen deprivation

ANSD and seizures

do not directly cause ANSD, but can be associated with neurological conditions that can cause ANSD, such as Friedrich's ataxia and Charcot-Marie-Tooth

ANSd with hyperbilirubinemia may be

reviersible/transient

bilirubin is a

neurotoxin that can pass through the blood-brain barrier

bilirubin can damage the

neurons and their connections within the auditory pathway disrupting the synchronized firing of the nerve fibers

it is unclear if restored neural synchrony at the brainstem level results in

normal auditory processing

diagnosis of ANSD includes

- careful case history

- OAEs including use of contralateral OAE suppression

- ABR

- ARTs

- behavioral assessment

- speech audiometry

- ECochG

- vestibular assessment

- functional assessment for young children (questionnaires)

the underlying pathophysiology of ANSD is seen on ABR waveforms that have

no measurable aspects

because ANSD causes there to be no measurable aspects on ABR,

none of the typical diagnostic measures of an ABR can be carried out

what should be present on ABR for patients with ANSD

cochlear microphonic

the cochlear microphonic is a response generated predominantly from the

OHCs

cochlear microphonic occurs approximately _____ ms after stimulus presentation

1 ms

cochlear microphonic ______ the phase of the stimulus

follows

cochlear microphonic shows a __________ shift from baseline with a rarefaction click stimulus

downward

cochlear microphonic shows a ________ shift from baseline with a condensation click stimulus

upward

combined use of OAEs and ABR with ______ ______ is essential for ANSD diagnosis

two polarities: condensation and rarefaction

use of alternating polarities _____ be used to diagnose ANSD

CAN'T

alternating polarities with ANSD will cancel out and produce

a flat line response

in patients with neuropathies without an ABR, CM may be

larger

in infants, the Cm may even continue over several milliseconds that stimulates an ABR response that is

artificial

all normal ABR waves increase in latency and decrease in amplitude as stimulus intensity

decreases

does cochlear microphonic increase in latency as the stimulus intensity decreases?

no

ABRs with no CM in ANSD are generally as result of either

instrumental or clinician error

or

use of an alternating polarity

ABR to diagnose ANSD is performed at a ____ level click stimulus using rarefaction and condensation polarity in separate trials

high

if there is no reversal of the waveform with reversal of polarity, if confirms

a true auditory nerve response

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

once an ANSD pattern (CM reversal) is identified, an ABR _____ be used to estimate an infant's hearing thresholds

CANNOT

hearing sensitivity with ANSD can range from

normal/mild to a severe to profound SNHL with varying configurations with fluctuations reported

hearing loss with ANSD can be

unilateral or bilateral

behavioral assessment becomes important for children with ANSD because

ABR cannot be performed for thresholds to fit amp with ANSD

patients with ANSd with normal or near-normal thresholds may still have significant impact on

speech perception because of IHC and CN VIII involvement

significant impact on speech perception with normal or near-normal thresholds with ANSD means the child is

functionally deaf

some children with ANSD with normal or near-normal thresholds may have relatively intact speech perception in quiet but

very poor in noise

age appropriate ________ testing is highly recommended when developmentally appropriate for children with ANSD

speech-in-noise

acoustic reflexes and ANSD

abnormal even with normal/mild SNHL because of auditory nerve/synapse involvement

~40% of children with ANSD had

vestibulopathy not associated with imaging findings

ECochG and ANSD

abnormal because APs generated by the VIII N are affected

assessments recommended for ANSD are similar to those for children with

SNHL

the 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

what other structure should be assessed if the ANSD is associated with peripheral neuropathies

eyes, ophthalmologic assessment

ANSD shows considerable variability in

auditory capabilities

hearing aids and assistive devices provided _____ benefits

limited

current recommendations for ANSD management include

trial of amplification if there is residual functional hearing

trial of FM system can reduce effects of

noise, distance, and reverberation especially in a classroom setting

educational management

continued and aggressive auditory and visual stimulation

manual communication

a formal education method to facilitate literacy/self-dependence

current most successful treatment for ANSD

cochlear implants

Children who do not demonstrate good progress in speech recognition and language development should be considered as candidates for ______ regardless of audiometric thresholds

CIs

in ANSD the question is not how severe the hearing loss is but how severe the ______ is

dys-synchrony

the pure tone audiogram is NOT an indicator of

severity of the dys-synchrony

CIs are successful for ANSd if the underlying pathophysiology is

biochemical abnormality of neurotransmitter substances

synaptic defects b/w IHC and auditory nerve

CIs are marginally successful for ANSD if neural integrity is compromised from

loss of myelin

loss of neural elements, including VIII N

gene therapy clinical trials are underway since late 2022 for deafness caused by

mutation of the OTOF gene (DFNB9 - ANSD)

is ANSD hearing loss pre or post lingual

both

hidden hearing loss

cochlear synaptopathy

loss/damage to synapses connecting the IHCs to the auditory nerve fibers (specifically type 1 afferent neurons of the spiral ganglion), which results in loss of temporal resolution

causes of cochlear synaptopathy

noise exposure

aging

ototoxic drugs

genetics

metabolic disorders

site of lesion for cochlear synaptopathy

the synapses, particularly ribbon synapses, which can subsequently lead to degeneration of CN VIII fibers

cochlear synaptopathy an affect

fine speech structure decoding and speech perception, especially in noise

difference between ANSD and Cochlear Synaptopathy

ANSD can also occur due to other causes along the auditory pathway between the cochlea and the brainstem, such as hypoplasia or absence of CN VIII