What is Auditory Neuropathy Spectrum Disorder?

This video provides an introduction to auditory neuropathy spectrum disorder (ANSD), and its pathophysiology, presentation and prevalence. You can read the full transcript below.

What is ANSD?

ANSD is a label defined by a characteristic set of results: Present OAE and/or cochlear microphonics with an absent or abnormal auditory brainstem response.

Many terms have been used to describe what is known as ANSD. Persistent outer hair cell function being one that focused on retained function. Another sought to describe the impairment such as auditory mismatch or auditory desynchrony.

The inclusion of the word spectrum is key to our understanding however, as it references the various etiologies, presentations, and potential outcomes.

Abnormal or absent ABR

Absent ABRs are easy to understand but an abnormal ABR can take many forms. Here in the right ear is an example of an abnormal ABR where waves III and V are clearly present but are much delayed. The top trace on the right-hand side shows an absent ABR.

Although it is clear that absent or abnormal ABRs are a core feature in ANSD, the reasons for the ABR findings are not clearly defined by the simple definition stated so far.

Present OAE and/or cochlear microphonic

As there are many more outer hair cells than inner hair cells, the cochlear microphonic response is dominated by outer hair cells. As is the OAE response. Present OAE and/or cochlear microphonics implies only the outer hair cell function is maintained and does not imply anything about inner hair cell function or synaptic function.

It's possible that the abnormal ABR response is due to dysfunction in the inner hair cells, afferent synapses to the spiral ganglion neurons, or the nerve fibers and central pathways themselves.

There are proposed mechanisms for each of these and there are also various etiologies, both genetic and acquired. It is also proposed that these various mechanisms and etiologies account for the variability of outcomes for those with ANSD.

We're now starting to build a very complex picture from a relatively simple pattern of diagnostic results.

ANSD pathophysiology

We can model the neural patterns to get a better understanding of proposed pathophysiology that leads to the ANSD pattern of results. Normal function, decreased input, and desynchrony will be discussed.

1. Normal function

We start with normal function. A signal is presented with a gap in between each pulse. Three nerve fibers are modeled here, all three of them firing in response to the signal. Each also has a resting background firing rate, which do not match up with any signal or with each other. The average response is seen at the top. The two signals are clearly identifiable against the background resting firing rate.

2. Decreased input

In the case of decreased input, we see the same signal being presented and this time only one of the three nerve fibers actually fires in response to the signal. It also has its resting firing rate as well.

Now, the average signal, it's very hard to see the response to the signal against the resting firing rate.

3. Desynchrony

And finally, neural desynchrony. Again, the same signal is presented and now although all three nerve fibers are firing, they're all firing at ever so slightly different times in response to the signal. They also all have different resting firing rates as well, but all of those are quite close together.

The average signal now has a response to the signal, but it is smeared as is the resting firing rate. It's very difficult to distinguish the response due to the signal against the background noise.

Prevalence of ANSD

ANSD occurs in 1 in 10 children with permanent hearing loss, and many of those are diagnosed in part due to a local newborn hearing screening protocol, especially when associated with these risk factors which often coincide with admittance to NICU:

• Extreme prematurity
• Low birth weight
• Ototoxic drugs jaundice
• Hypoxic ischemic encephalopathy
• Intraventricular hemorrhage
• Anoxia respiratory distress and ventilation

It should be noted here that some of these risk factors are related to delayed maturation and as such, attention should be paid to the possibility of so-called transient ANSD. Despite the majority of cases being found early on, it's not always the case that children are diagnosed immediately after birth, especially when babies are often screened only by OAE, which is the case in a proportion of screening programs.

Presentation of ANSD

As such, there are additional factors of presentation that might warrant additional testing and monitoring as the child develops, such as:

• Delayed speech
• Difficulty hearing in noise, especially where behavioral thresholds do not suggest these challenges might occur
• In the small population, fluctuating hearing or fluctuating behavioural thresholds

Referral patterns

In respect to history, you'll likely see patients referred from NICU screening programs or parental concern, all of which will warrant diagnostic ABRs if the pattern of results suggest potential ANSD.