The outcome of cochlear implantation in otoferlin-related cochlear synaptopathy

Objectives Auditory neuropathy is a hearing disorder characterized by disruption of the temporal coding of acoustic signals in the auditory fibers, which results from alterations at pre- and post-synaptic sites. The most well- known pre-synaptic form of AN is associated with mutations in the OTOF gene encoding otoferlin, a transmembrane protein involved in neurotransmitter release at the IHCs ribbon synapses. The aim of this study was to evaluate the performance of cochlear implantation in a group of children carrying biallelic pathogenic mutations in the OTOF gene. Methods Ten children and one adult were considered (7 females). All had congenital hearing loss, which was profound in 8 patients and mild in 3 subjects. Profoundly deaf children underwent unilateral cochlear implantation at the age of 2.5±0.9 years, while patients with mild hearing loss received the cochlear implant at ages of 4, 7 and 28 years respectively. Hearing thresholds with the use of cochlear implant (pure tone average at 0.5-1-2-4 kHz, PTA), speech recognition thresholds (SRT), open-set recognition of disyllabic words and sentences and identification of consonants were periodically evaluated, the maximum follow up duration extending from 3 to 16 years. Electrically-evoked compound action potentials (ECAPs) were also recorded, and response thresholds and slopes of the input-output curves were compared to the values obtained from a control group including 15 implanted children harboring mutations in the GJB2 gene. Results At the last follow up evaluation, mean PTA attained 24.7±4.4 dB, while SRT was 31.0±5.6 dB. Open-set recognition scores were respectively 94.8±4.7% and 96.6±3.7% for disyllabic words and sentences, while score on consonant identification was 83.6±10.3%. ECAP thresholds were comparable to the values obtained in children harboring mutations in the GJB2 gene, whereas the slopes of the input-output ECAP curves were higher in patients with OTOF-related hearing impairment. Conclusion Cochlear implants are effective in restoring hearing sensitivity and speech perception in patients with OTOF- related profound deafness. The use of cochlear implants results in a remarkable improvement of speech perception also in OTOF patients showing mild hearing impairment. ECAP recordings indicate preservation of the auditory nerve function and restoration of synchronous activation of the auditory fibers.