Severe to profound sensorineural hearing loss (SNHL) requires cochlear implantation (CI) for auditory rehabilitation. Etiologic diagnoses can contribute to candidacy selection and decision-making regarding the timing of successful CI. However, few studies have been performed to address the etiologic spectrum of severe SNHL in the population where there is no consanguineous marriage and the majority of SNHL cases are sporadic in small sized families. The authors sought to comprehensively understand the etiologies of Korean cochlear implantees by incorporating the targeted resequencing of 204 candidate deafness genes (TRS-204) and a phenotype-driven candidate gene approach. Ninety-three that consented to molecular genetic testing and underwent at least one molecular genetic test were included. Patients with a characteristic Phenotypic marker were subject to Sanger sequencing to detect variants in corresponding candidate genes. The rest of patients without any prominent phenotype were tested on GJB2. Next, TRS-204 was applied in GJB2-negative cases without any phenotypic marker. In addition, the sibling recurrence-risk of SNHL among families with non-diagnostic genotypes after TRS-204 was performed to gain insight of etiologies in non-diagnostic cases. Overall, we could find causative variants in 51 (54.8%) of the 93 cochlear implantees. Thirty (32.3%) probands could be diagnosed by direct Sanger sequencing of candidate genes selected by their phenotypes. GJB2 sequencing added 10 subjects to the group with a diagnostic genotype. TRS-204 could detect a causative variant from additional 11 cases (11.8%). We could not detect any pathogenic deletion or duplication on 204 target genes. The sibling recurrence-risk of SNHL among 42 genetically undiagnosed families with 0.03 (1/38) was significantly lower than among genetically diagnosed recessive families with 0.19 (7/37). Despite that the majority of severe or more degree of SNHL occurs sporadically in Koreans, at least 54.8% of such cases that were willing to join the genetic study in the Korean population are monogenic Mendelian disorders with convincing causative variants. This study also indicates that a substantial portion of unsolved cases after applying our current protocol are predicted to have non-genetic or complex etiology rather than a Mendelian genetic disorder involving new genes beyond the 204 target genes.

Sensory plasticity, which is associated with deafness, has not been as thoroughly investigated in the adult brain as it has in the developing brain. In this study, we examined the brain reorganization induced by auditory deprivation in people with adult-onset deafness and its clinical relevance by measuring glucose metabolism before cochlear implant (CI) surgery. F-18 fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) scans were performed in 37 postlingually deafened patients during the preoperative workup period, and in 39 normal-hearing (NH) controls. Behavioral CI outcomes were measured at 1 year after implantation using a phoneme identification test with auditory cueing only. In the deaf individuals, areas involved in the auditory pathway such as the inferior colliculus and bilateral superior temporal gyri were hypometabolic compared to the NH controls. The hypometabolism observed in the deaf auditory cortices gradually returned to levels similar to the controls as the duration of deafness increased. However, contrary to our previous findings in congenitally deaf children, this metabolic recovery failed to have a significant prognostic value for the recovery of the speech perception ability in adult CI patients. In a broad occipital area centered on the primary visual cortices, glucose metabolism was higher in the deaf patients than the controls, suggesting that the area had become visually hyperactive for sensory compensation immediately after the onset of deafness. In addition, a negative correlation between the metabolic activity and behavioral speech perception outcomes was observed in the visual association areas. In the medial frontal cortices, cortical metabolism in most patients decreased, but patients who had preserved metabolic activities showed better speech performance. These results suggest that the auditory cortex in people with adult-onset deafness is relatively resistant to cross-modal plasticity, and instead, individual traits in late-stage visual processing and cognitive control seem to be more reliable prognostic markers for adult-onset deafness.

The outcome of cochlear implantation (CI) in patients with cochlear nerve deficiency (CND) is variable, resulting in a wide range of speech perception performance, from degrees of environmental sound perception to conversation without lip-reading. Twenty-five cochlear implantees with CND were enrolled retrospectively to determine the factors correlated with CI outcome in patients with CND and to develop a predictive model for CI outcome. CI outcome was evaluated using the Categories of Auditory Performance (CAP) score at 2 years after CI. Patients with negative auditory brainstem response (ABR) showed a significantly lower CAP score than those with positive ABR (2.5 ± 1.7, 4.8 ± 0.7; p = 0.001). The area ratio of vestibulocochlear nerve (VCN) to facial nerve (FN) at the cerebellopontine angle on magnetic resonance images was positively correlated with CI outcome (p < 0.001). With multiple regression analysis, a predictive equation accounting for 66% of variance of CAP score at 2 years after CI was $${\bf{deduced}}:{\bf{CAP}}\,{\bf{score}}{\boldsymbol{=}}{\bf{0.7}}{\boldsymbol{+}}{\bf{1.9}}{\boldsymbol{\ast }}{\boldsymbol{(}}{\bf{ABR}}{\boldsymbol{)}}{\boldsymbol{+}}{\bf{1.2}}{\boldsymbol{\ast }}(\frac{{\boldsymbol{V}}{\boldsymbol{C}}{\boldsymbol{N}}}{{\boldsymbol{F}}{\boldsymbol{N}}})$$deduced : CAP score = 0.7 + 1.9 ∗ ( ABR ) + 1.2 ∗ ( V C N F N ) . We found that preoperative ABR and area ratio of VCN to FN at the cerebellopontine angle could predict CI outcome in patients with CND. Preoperative counselling based on our predictive model might be helpful to determine treatment modality for auditory rehabilitation and which ear to implant.