Abnormal Cochlear Potentials recorded by Transtympanic Electrocochleography from Patients with Auditory Neuropathy due to Mutations in the Otoferlin or OPA1 gene

Auditory neuropathy (AN) is a disorder characterized by disruption of auditory nerve activity resulting from lesions involving the auditory nerve, inner hair cells (IHCs) and/or the synapses. Affected subjects show impairment of speech perception beyond that expected for the hearing loss, abnormality of auditory brainstem potentials and preserved outer hair cell activities (otoacoustic emissions and/or cochlear microphonic, CM). Abnormal neurotransmitter release from IHCs has been proposed as the mechanism underlying AN in patients with mutations in the OTOF gene (pre-synaptic AN), while disruption of auditory nerve function may underlie the disorder with OPA1 mutations (post-synaptic AN). Transtympanic electrocochleography was recorded from 4 children with OTOF mutation and 2 adults with mutation in the OPA1 gene. Cochlear potentials to clicks were compared to recordings obtained from 16 normally hearing children. Electrically-evoked compound action potentials (CAPs) were also obtained following cochlear implantation. Cochlear neural potentials were of negative polarity with reduced amplitude and prolonged duration compared to controls. The prolonged potentials were recorded as low as 50-90 dB below behavioral thresholds in subjects with OTOF mutation whereas in patients with OPA1 mutation they were correlated with behavioral threshold. Auditory CAPs were superimposed on the prolonged responses in 3 subjects with OTOF mutations at high stimulus intensity while they were absent in OPA1 disorder. Electrically-evoked CAPs were only recorded from children with OTOF mutations. In subjects with OTOF mutations the low-threshold prolonged potentials are consistent with abnormal neurotransmitter release resulting in reduced dendritic activation and impairment of spike initiation whereas the lack of CAPs in OPA1 is consistent with abnormal function of distal portions of auditory nerve fibers.