Pathophysiological mechanisms and functional hearing consequences of auditory neuropathy

Abstract

The effects of inner ear abnormality on audibility have been explored since the early 20th century when sound detection measures were first used to define and quantify 'hearing loss'. The development in the 1970s of objective measures of cochlear hair cell function (cochlear microphonics, otoacoustic emissions, summating potentials) and auditory nerve/brainstem activity (auditory brainstem responses) have made it possible to distinguish both synaptic and auditory nerve disorders from sensory receptor loss. This distinction is critically important when considering aetiology and management. In this review we address the clinical and pathophysiological features of auditory neuropathy that distinguish site(s) of dysfunction. We describe the diagnostic criteria for: (i) presynaptic disorders affecting inner hair cells and ribbon synapses; (ii) postsynaptic disorders affecting unmyelinated auditory nerve dendrites; (iii) postsynaptic disorders affecting auditory ganglion cells and their myelinated axons and dendrites; and (iv) central neural pathway disorders affecting the auditory brainstem. We review data and principles to identify treatment options for affected patients and explore their benefits as a function of site of lesion.

Remodeling of the Inner Hair Cell Microtubule Meshwork in a Mouse Model of Auditory Neuropathy AUNA1

“…Up to now, defective transmitter release is the most prevalent mechanism to cause human auditory neuropathies (Rance and Starr, 2015). However, synaptic recycling and the number of ribbon synapses were not affected in the diap3-overexpressing mutants, which excludes the loss of the ribbon synapses as a primary cause of AUNA1 deafness, as previously described (Schoen et al, 2013).…”

“…Auditory neuropathy is a form of human deafness in which the auditory brainstem response (ABR) is absent or altered, while outer hair cells (OHCs), which amplify the sound stimulation in the cochlea, are still preserved (Starr et al, 1996; Rance and Starr, 2015). A variety of etiologies may result in this disorder, including defects in cochlear inner hair cells (IHCs) that transduce sound stimulation into neurotransmitter release, and defects or absence of the auditory afferent fibers that convey the neural message to the cochlear nuclei.…”

Genetic variants in the peripheral auditory system significantly affect adult cochlear implant performance

“…These physiologic measures were found to be predictive of postoperative audiometric outcome and could account for 40% of the variance in outcome in 32 adult CI recipients (McClellan et al, 2014). In addition, CI recipients with auditory neuropathy spectrum disorder generally have relatively poor CI outcomes (Blamey et al, 2013; Rance and Starr, 2015). These data implicate the health of the spiral ganglion as an important factor in CI outcomes.…”

A Case of Auditory Neuropathy Caused by Pontine Hemorrhage in an Adult

“…The axonal or demyelinating lesion of the auditory nerve are known to be the major pathophysiology of auditory neuropathy, which results in the failure of precise synchronization of the action potential generated at each nerve fiber and cause abnormal ABR waveforms [16]. Pontine hemorrhage can affect the ABR waveform because a duration of acute nerve compression of over 2 hours can cause Wallerian degeneration of neural tissue; if more time passes, extensive neural degeneration results [17].…”