Abstract
The present study focuses on DFNA9, an autosomal dominant disorder caused by pathogenic variants in the COCH gene. These mutations induce the formation of aggregates that are toxic to the fibrocytes in the extracellular matrix, ultimately leading to degeneration of spiral ganglion neurons (SGNs), which are crucial for transmitting auditory
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signals from the cochlea to the brain. An important tool for evaluating the function of the SGNs, which are the target cells of a cochlear implant (CI), is the electrically evoked compound action potential (eCAP). Therefore, the main objective is to evaluate the eCAP to describe the function of the SGNs and study cochlear health in CI patients with DFNA9. For this reason, we included 15 carriers of the p.Pro51Ser variant in the COCH gene who received a MED-EL CI (DFNA9 group) and 15 matched control CI subjects without DFNA9 to compare the impedances and subsequently the threshold, amplitude and slope of the eCAP amplitude growth function (AGF). These parameters were evaluated from intraoperative autoART recordings (MED-EL) during CI surgery. Matching of the two groups was based on sex, age at implantation, duration of deafness, and type of implant. The first results, regarding the difference in impedance between DFNA9 and non-DFNA9 patients, show a significant interaction between time and group in the middle and basal electrodes, indicating that electrode impedances were similar in the early phase after implantation between the two groups, but increased significantly more for the DFNA9 group up to one year after implantation. Secondly, the results show that the success rate (present or absent) to record eCAP responses is lower in the DNFA9 group: eCAPs were detectable in 75.5 % of the intraoperative measurements (145/192) in comparison to 96.9 % (186/192) in the group without DFNA9. ECAP absence in the DFNA9 group was observed across the whole electrode array, but more pronounced in the basal region (channels 11 and 12). Additionally, comparing the parameters of the AGF, the maximum eCAP amplitude was consistently smaller and the AGF slope consistently shallower for the DFNA9 group compared to the control group throughout the entirety of the electrode array. Finally, the eCAP thresholds in patients with DFNA9 were higher compared to those in the control patients for all cochlear locations. To our knowledge, this is the first study to investigate the eCAP measurements in patients with DFNA9. As proven in the literature, eCAP measures correlate well with the health and survival of SGC. This means that the results of our study predominantly suggest that DFNA9 leads to an even stronger reduction in excitability and neuronal health than seen in other causes of deafness.
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