OPA1-related auditory neuropathy: site of lesion and outcome of cochlear implantation

Abstract

Santarelli et al. reveal that hearing impairments in patients carrying OPA1 missense mutations are the result of disordered synchrony in auditory nerve fibre activity owing to degeneration of terminal dendrites. Cochlear implantation improves speech perception and synchronous activation of auditory pathways in these patients by bypassing the lesion site.

Auditory neuropathy — neural and synaptic mechanisms

“…For example, electrocochleography results in similar find ings for patients with OPA1-associated auditory neuro pathy and OTOF-associated auditory synapt opathy 74,127 . Moreover, in animal models of auditory synaptopathy and neuropathy, the delayed and broadened compound action potentials can arise from either presynaptic 16,17,128 or post synaptic 21 defects.…”

“…Neuropathic hear ing impairments are common findings among indivi duals with syndromic dominant optic atrophy caused by mutations in the gene optic atrophy 1 (OPA1) 74,75 . Dominant optic atrophy is one of the most frequent genetic optic atrophies, and OPA1 mutations are causal in the majority of the cases 76 .…”

“…Detailed audiological assessment with transtympanic electrocochleography (FIG. 1) indicates normal function of IHCs and OHCs, but a failure of SGN activation in the cochlea, indicative of auditory neuro pathy 74 . On the basis of the specific pattern of remaining neural responses, DOA+ related hearing impairment was postulated to result from degeneration of the peripheral neurite of the SGNs.…”

“…On the basis of the specific pattern of remaining neural responses, DOA+ related hearing impairment was postulated to result from degeneration of the peripheral neurite of the SGNs. Indeed, most of the individuals with DOA+ who received a cochlear implant had very good rehabilitation outcomes 74 . To date, no hearing deficits have been reported in Opa1 mutant mice, which carry a splice site mutation that probably causes DOA via haplo insufficiency 81 .…”

Auditory nerve disease and auditory neuropathy spectrum disorders

“…Various hypotheses of the pathophysiology of AN are proposed: presynaptic or postsynaptic disorders of synapses between inner hair cells and the cochlear nerve, desynchronization within the cochlear nerve, demyelination or axonal atrophy of the cochlear nerve. Genetic mutations in AN involving OTOF, OPA1 and other genes have been reported [27,28]. However, there is the possibility of unknown mutations because the reported gene mutations are not commonly detected.…”