| Home | E-Submission | Sitemap | Contact Us |  
Clinical and Experimental Otorhinolaryngology > Volume 15(4); 2022 > Article
Kim and Choi: Precision Medicine Approach to Cochlear Implantation

Abstract

In the early days of cochlear implantation (CI) surgery, when the types of electrodes were limited and the etiology of sensorineural hearing loss (SNHL) was not well understood, the one-size-fits-all approach to CI held true, as in all other fields. However, in the era of personalized medicine, there have been attempts to associate CI performance with the etiology of SNHL and to establish customized surgical techniques that can maximize performance according to individual cochlear dimensions. Personalized genomic-driven assessments of CI candidates and a better understanding of genotype-phenotype correlations could provide clinically applicable diagnostic and prognostic information about questions such as who, how, and when to implant. Rigorous and strategic imaging assessments also provide better insights into the anatomic etiology of SNHL and cochlear dimensions, leading to individualized surgical techniques to augment CI outcomes. Furthermore, the precision medicine approach to CI is not necessarily limited to preoperative planning, but can be extended to either intraoperative electrode positioning or even the timing of the initial switch-on. In this review, we discuss the implications of personalized diagnoses (both genetic and nongenetic) on the planning and performance of CI in patients with prelingual and postlingual SNHL.

INTRODUCTION

For subjects with severe-to-profound hearing loss who no longer benefit from the use of hearing aids, cochlear implantation (CI) is a better habilitation method for improved speech outcomes [1]. CI is a commonly performed procedure with continuously expanding indications. Speech performance after CI is influenced by a complex array of factors, including the duration of hearing loss, age at implantation, residual hearing, age at onset of hearing loss, type of implant, and socioeconomic status [2,3]. Unfortunately, approximately 3%–7% of cochlear implantees do not benefit from the use of their device [4,5]. Although realistic expectations for CI performance can be predicted to some extent based on prognostic factors, no methods are currently available to identify these potential nonusers prior to surgery.
In the era of personalized medicine, attempts have been made to associate CI performance with the etiology of hearing loss [6-8] and to establish surgical techniques that can maximize performance according to individual cochlear dimensions [9,10]. In this review, we discuss the implications of a personalized diagnosis (both genetic and nongenetic) and how it relates to the performance of CI and decision-making in patients with prelingual and postlingual hearing loss (Table 1) [6-8,11-49].

MOLECULAR GENETIC DIAGNOSIS AND CI IN PRELINGUAL DEAFNESS

The introduction of next-generation sequencing technology has allowed implementation of genetic diagnosis in various fields of medicine, including hearing loss [50,51]. Molecular genetic testing (MGT) has now become an important step in the diagnostic workup of CI candidates, providing invaluable information regarding the etiology of hearing loss and the prognosis of CI [11]. This information can predict the natural course of hearing loss, guide patient selection, and aid in determining the timing of CI [52-54].
Hereditary deafness with variants in certain genes is related to especially successful CI outcomes; in particular, CI yields excellent results in patients who have congenital deafness with variants of GJB2 or SLC26A4, the two most common deafness-causing genes [12-14,55,56]. Wu et al. [13,14] found that age at implantation was another important predictor of favorable CI outcomes even in patients with pathogenic variants of GJB2 and SLC26A4, which are genes that allegedly have a good prognosis. Children that received CI before the age of 3.5 years demonstrated better auditory performance at 3 and 5 years post-CI than those without documented pathogenic variants, whereas no significant differences were observed between children that received CI after 3.5 years of age [13,14].
However, in another study of Korean children with GJB2 and SLC26A4 variants who underwent CI, excellent results were also observed in late cochlear implantees [12]. The discrepancy in these findings is attributed to the fact that most late implantees, especially children with SLC26A4 variants, had a history of progressive or fluctuating hearing loss and their pre-CI hearing experience could be associated with their good CI outcomes.
Furthermore, subjects with auditory neuropathy spectrum disorder (ANSD) segregating OTOF variants (DFNB9) showed consistent benefits from CI when implanted at an appropriate age [15]. However, the sensitive period for good CI outcome for DFNB9 individuals may be narrower than that for GJB2- and SLC26A4-related deafness [12,16-18]. Fifty percent of Korean DFNB9 children implanted after 2 years of age showed notably poor outcomes (categories of auditory performance [CAP] scores of 3 and 4) at 24 months post-CI, unlike the CAP scores of 6 and 7 achieved by children implanted early [12]. Furthermore, implantation before the age of 18 months was associated with a more rapid catchup in speech ability after CI [19]. In a recent pilot study investigating the central auditory development of DFNB9 patients after CI, the cortical auditory evoked potential-based P1 components of children implanted after the age of 2 years tended to be “absent” or “anomalous,” almost always associated with delayed language development [17]. Another interesting finding was that when the P1 component was repeatedly measured in DFNB9 patients, even the children who underwent timely implantation (before the age of 12 months) did not achieve sufficient cortical maturation with 6–7 months of device use. This suggests the need for sustained rehabilitation in DFNB9 patients compared to patients with other molecular etiologies.
Bi-allelic PCDH15 pathogenic variants and the p.G292R variant of DFNB59 are reported to be associated with poor CI performance [13]. Pejvakin-deficient mice and humans have been shown to be hypervulnerable to sound because they lack the oxidative stress-induced pejvakin-dependent proliferation of peroxisomes, which contributes to the physiological response to sound exposure [57]. The amplification of sound using hearing aids or CIs may paradoxically worsen hearing impairment in patients with DFNB59 due to sustained injury to the hair cells, spiral ganglion neurons (SGNs), and the auditory nerve by uncontrolled oxidative stress; therefore, the authors suggested antioxidant protection in cases of peroxisomal deficiency, for specific protection against redox homeostasis failure [57].
All in all, implantees with an identified genetic etiology tend to achieve better speech outcomes than those with an unidentified etiology [6,7,12], although some variants are related to poor CI outcomes [13]. The information acquired from MGT can also be used to counsel patients and their families on expected outcomes after CI and the time required to reach those results. MGT can also identify appropriate candidates for personalized and customized auditory rehabilitation among deaf patients.

CI IN CONGENITAL CYTOMEGALOVIRUS INFECTION

Congenital cytomegalovirus (cCMV) infection is a common congenital infection, found in 0.5% to 2% of all live births [58,59]. Some children with cCMV infection can manifest permanent disabilities, including sensorineural hearing loss (SNHL), vision loss, and neurodevelopmental delay, with SNHL being the most common manifestation [60]. Based on the presence of clinical manifestations at birth, cCMV infection can be classified as symptomatic or asymptomatic. Approximately 10% of neonates with cCMV infection are symptomatic (i.e., they are born with clinically apparent sequelae), while the remaining 90% are asymptomatic at birth [61]. However, about 6%–23% of neonates with asymptomatic cCMV infections can also develop late-onset SNHL, while 33%–63% of symptomatic patients develop SNHL [60,62,63].
Resultantly, cCMV infections account for approximately 40% of cases of nongenetically caused congenital SNHL, representing about 20% of all congenital SNHL [64]. A substantial proportion of SNHL cases due to cCMV infections manifest as asymmetrical and progressive hearing loss with significant residual hearing [65]. Indeed, in a study of audiological characteristics in a Korean cohort with cCMV infections, 33.3% of patients had SNHL, 38% had asymmetric hearing loss, 29% had late-onset hearing loss, and there was a diverse spectrum of SNHL severity, ranging from mild to profound [66,67].
Children with significantly delayed speech development due to cCMV-related SNHL are also potential candidates for CI. However, predicting the outcome of prelingual bilateral profound hearing loss due to cCMV infection is not straightforward. Some studies have shown that cCMV patients can achieve comparable CI outcomes to those with idiopathic SNHL [68,69] or SNHL caused by GJB2 variants [70,20]. However, other studies have reported variable outcomes of CI [71,72]. Specifically, Lee et al. [21] found that 64% of children with CMV-related hearing loss were able to recognize open-set words after 4 years of device use, suggesting a wide spectrum of outcomes. Similarly, Viccaro et al. [73] showed that after around 10 years of CI usage, the ability to recognize open-set words improved in most patients. This wide spectrum of outcomes could be attributed to neurodevelopmental delay and cognitive impairment, which can also manifest as a result of cCMV infection. In this sense, brain abnormalities seen on magnetic resonance imaging are considered poor prognostic markers of speech performance after CI [20,22], although they have been shown to be correlated with CI outcomes to some extent [23]. In detail, patients with normal white matter or partial white matter abnormalities on magnetic resonance imaging showed good speech perception performance after CI, at least comparable to the performance obtained by idiopathic SNHL patients [23].
The decision to perform CI in patients with unilateral and asymmetric hearing loss due to cCMV infection is even more complicated. In these cases, since substantial speech development has already been achieved, the decision to perform implantation should be determined by weighing the potential benefits for speech development (i.e., pronunciation or expressive language) that can be obtained through CI against the limitations of development due to cognitive impairment. Specifically, we need to be cautious about performing CI on the worse-hearing ear in a cCMV child with asymmetric hearing loss who has significant cognitive impairment.

CI IN COCHLEAR NERVE DEFICIENCY

Cochlear nerve deficiency, typically defined as a small or absent cochlear nerve in the internal auditory canal (IAC) documented by magnetic resonance imaging, is a known cause of congenital deafness [74,75] and is prevalent in up to 18% of congenital SNHL [76]. The status of the cochlear nerve can be graded based on the number of nerves visualized in the IAC [77]. Grade 0 is defined as no nerves identified in the IAC, grade I as one nerve being present, grade II as two nerves being present, grade III as three nerves being present, grade IV as four nerves being present with a hypoplastic nerve, and grade V as all four normal sized nerves being present in the IAC [77]. However, the limited resolution of magnetic resonance imaging may not accurately reflect the status of the nerves in the IAC [78] and some patients with auditory nerve aplasia do, in fact, respond to electrical stimulation when implanted with a CI [79,80].
The management of hearing loss in children with cochlear nerve deficiency involves many challenges. Because the cochlear nerve is absent or hypoplastic, the electrical signal from the implant provides limited stimulation. Cochlear nerve deficiency can accompany other inner ear malformations, craniofacial anomTable alies, and neurodevelopmental problems, which further influence the outcomes of CI [81,82]. Cochlear nerve deficiency was once considered a contraindication for CI [83], but a growing body of evidence suggests successful CI outcomes in these patients despite imaging evidence of deficient cochlear nerves [24].
Children with cochlear nerve deficiency obviously require higher stimulation levels than those required by those with normal cochlear nerve dimensions [25-27]. These results support the importance of (1) proper device choice (e.g., modiolar hugging electrodes with better modiolar proximity) and (2) appropriate initial switch-on strategies to ensure the earlier stabilization of mapping parameters, thereby maximizing the patients’ performance [28,29].

CI IN COMMON CAVITY OR COCHLEAR APLASIA WITH DILATED VESTIBULE: EXPLORING THE NEURAL TISSUE

CI is generally considered a valid option for common cavity (CC) deformities [84,85], albeit with varying outcomes reported to date. Cochlear aplasia with dilated vestibule (CADV) is traditionally regarded as a contraindication to CI; nonetheless, some satisfactory outcomes have been reported in very small numbers [86,87]. For patients with CC or CADV, the status of the cochlear nerve and the positioning of the electrode can potentially affect CI outcomes [85].
Auditory neural tissues are distributed along the wall of these anomalous cavities [88], which is in line with the clinical observation that a full-band straight electrode outperforms modiolar hugging electrodes in eliciting electrically evoked compound action potential (ECAP) responses in patients with CADV who have undergone CI [30]. Using electrical auditory brainstem response recordings, Yamazaki et al. [89] determined that the auditory neuronal tissue was distributed in the anteroinferior part of CC deformities, mainly near the inner wall of the cavity in all cases. The authors suggested using electrical auditory brainstem response testing to achieve the optimal electrode array placement and to adjust the programming parameters of the implanted device.
During CI surgery for CC/CADV, the electrode should be inserted in a way that enables maximum contact of the CI electrode with the inner wall of the cavity [30,31]. In a previous study, a lower maximum comfortable level and better behavioral outcomes were related to a shorter distance between the inner wall of the CC/CADV cavity and the electrode [90]. Intraoperative ECAP-based positioning of full-band straight electrodes can be implemented in surgical practice to guide the optimal electrode positioning in each individual CC/CADV, allowing successful CI [30].
Taken together, achieving the best possible CI outcomes in CC/CADV depends on the presence of auditory neural tissue and proper positioning of the electrode, which could be assisted by ECAP measurements so that the neural tissues can be fully stimulated.

MOLECULAR GENETIC DIAGNOSIS AND CI IN POSTLINGUAL DEAFNESS

Some genetic variants have been reported to be associated with good auditory performance after CI in postlingual deafness [32, 91,92]. Therefore, identification of pathogenic variants via MGT can be a crucial component in the preoperative evaluation of CI from a prognostic viewpoint. For example, CI is believed to provide satisfactory results in postlingual adult DFNA9 cochlear implantees carrying a variant of COCH that is also expressed in the dendrites of the SGN, in addition to the spiral limbus and the lateral wall [33]. Pecci et al. [34] reported that CI was safe and effective in most patients with MYH9-related disease and deafness. Miyagawa et al. [11] found that four patients with a variant in the MYO15A, TECTA, TMPRSS3, or ACTG1 genes showed relatively good auditory performance after CI including electric acoustic stimulation.
A comprehensive MGT protocol, including exome sequencing, can potentially identify the genetic etiology in approximately 50% of patients with postlingual deafness [8]. Molecular etiologic heterogeneity involving 14 deafness-related genes in 21 subjects was noted in this Korean cohort [8]. Whereas variants of two genes, GJB2 and SLC26A4, account for a high proportion (up to 38%) of prelingual SNHL [12], there is extreme genetic heterogeneity in postlingual deafness [32,91]. Given the nature of this heterogeneity, exome sequencing is often required to identify pathogenic variants.
Implantees whose causative variants were identified among known deafness-related genes yielded better CI outcomes than those without identifiable variants [8]. However, considerable variation in CI outcomes was observed among subjects with the same genotype, meaning that the genetic etiology alone may not be sufficient for predicting CI outcomes. The duration of deafness is negatively associated with CI outcomes, especially in subjects with identified causative variants among known deafness-related genes, but not in those who remain undiagnosed. Therefore, timely CI is recommended in subjects with a known genetic etiology.
CI outcomes are also related to the gene expression site in postlingually deafened cochlear implantees [35]. A classic hypothesis postulated that CI outcomes could be predicted based on SGN health [32]. Membranous labyrinth-related deafness genes, which may inflict relatively weaker damage on the SGN health if mutated, are considered to yield favorable CI outcomes [8]. Furthermore, even subjects with SGN-related deafness genes, including COCH [33], TMPRSS3 [36], and NF2 [37], can attain some extent of audiological benefit from CI.

POSTLINGUAL ANSD AND CI

Perhaps the most substantial beneficiaries of the precision medicine approach to CI are patients with postlingual ANSD. Unlike prelingual ANSD, which is mainly caused by OTOF variants or cochlear nerve deficiency, numerous causative genes of postlingual ANSD have been reported. These genes are broadly divided into genes expressed in (1) inner hair cells themselves, (2) inner hair cell-afferent dendrite junctions, and (3) regions more central to the inner hair cell-afferent dendrite synaptic junctions, depending on their expression sites.
A representative ANSD-related gene expressed only in inner hair cells itself is DIAPH3, which causes lesions limited to the stereocilia of inner hair cells [38]. Many currently known ANSD-related genes are usually expressed at the inner hair cell-afferent dendrite junction. For example, SLC17A8, which encodes VGLUT3, and DMXL2, which encodes rabconnectin-3, are expressed in the synaptic vesicle membrane and are known to cause, if altered, DFNA25 and DFNA71, respectively, in humans [39,40]. In addition to genes expressed in the inner hair cells and the junction itself, some genes are expressed in the supporting cells adjacent to the inner hair cells such as border cells and inner phalangeal cells. The classic example of this is TMEM43 [41]. It is not surprising that favorable CI outcomes are reported among these presynaptic ANSD cases that are not amenable to conventional hearing aids.
Two genes, ATP1A3 and OPA1, merit special attention since these are known to cause syndromic hearing loss. ATP1A3 is the causative gene of CAPOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and SNHL); however, the p.Glu818Lys variant of ATP1A3 was found to lead to a manifestation of ANSD with minimal syndromic features in Koreans. In fact, it frequently appears in the form of nonsyndromic ANSD [42]. Since ATP1A3 and OPA1 are expressed in the spiral ganglia, as well as in the nerve endings of afferent dendrites, the results of CI have been questioned, but satisfactory results have been reported [42,43].
In contrast, when ANSD occurs due to alteration of genes mainly expressed more central to the synaptic region (e.g., the SGN or the cochlear nerve) the outcome of CI is theoretically unpredictable, with residual hearing at risk of aggravation. There are no definitive data on whether these ANSD patients can benefit substantially from CI. Given the lack of a robust clinical test to localize the main lesion of postlingual ANSD, molecular genetic diagnosis is of tremendous importance for predicting the outcomes of CI and sometimes even for deciding whether to perform CI in these patients.

POTENTIALLY TREATABLE SNHL AND CI

The management of hearing loss in a subclass of patients with progressive SNHL due to gain-of-function variants of the NLRP3 gene warrants special attention. The NLRP3 gene encodes the NLRP3 protein, which controls the secretion of interleukin (IL)-1β [93]. The cochlear autoinflammation caused by increased levels of IL-1β in these patients can thus be reversed by systemic administration of an IL-1β antagonist [94]. The degree of hearing loss, and the responsiveness to the IL-1β antagonist (Kineret [anakinra]) may vary from person to person; however, the NLRP3 genotype, auditory thresholds at diagnosis, and radiological findings of the cochlea can collectively serve as potential predictive and prognostic factors of hearing loss progression [95]. Not infrequently, CI candidates with NLRP3 variants show improvement in hearing to a level that can be rehabilitated with conventional hearing aids after daily injections of anakinra, emphasizing the importance of molecular genetic diagnosis in the management of hearing loss. Patients unresponsive to medical therapy nevertheless show excellent audiological outcomes with rapid improvement in speech perception test results, reaching a plateau at 3 months after CI [44].

MOLECULAR GENETIC DIAGNOSIS AND HEARING PRESERVATION IN CI AMONG SKI-SLOPE TYPE HEARING LOSS

A subset of postlingual hearing loss patients exhibits ski-slope type hearing loss—hearing loss with significant low-frequency residual hearing. These patients are in a unique situation because hearing aids do not provide adequate amplification of the mid-to-high frequencies necessary for speech perception; however, many of these patients also do not meet the reimbursement criteria for the insurance system and sometimes do not fall within the conventional candidacy criteria for CI. Therefore, a clinical dilemma exists regarding the decision of when to proceed with CI, and the precision genetic medicine approach can guide decision-making. Specifically, a recent case series describing the effects of CI in children with TMPRSS3 variants has paved the way for the idea of early interventions using electroacoustic stimulation implants in cases where the natural course of hearing loss can be predicted by the genetic etiology [45].
The detection rate of MGT in a Korean cohort of ski-slope hearing loss patients was 37.8% [46]. This number is significantly lower than detection rates of 48%–65% previously reported for SNHL cases diagnosed through the same molecular diagnostic platform [8,53,96]. Considering that around 80% of hearing loss cases are of genetic origin [97], there may be a yet-to-be-found Mendelian genetic disorder behind ski-slope hearing loss. Alternatively, environmental or polygenic factors could play a role in the pathophysiology of ski-slope hearing loss. Nevertheless, the variants found in a ski-slope hearing loss cohort were heterogeneous and included TMC1, TMPRSS3, GSDME, MYO3A, MYO6A, MYO7A, MYO15A, LOXHD1, PTPRQ, SLC26A4, P2RX2, LRTOMT, and USH2A and GPR98 digenic variants [46].
Minimally invasive surgery and delicate electrode array designs have recently allowed hearing preservation in CI surgery, although the hearing preservation rate differs according to studies [98-100]. A trend toward better hearing preservation in genetically diagnosed cochlear implantees has been proposed, especially in patients carrying pathogenic variants of genes specifically expressed in the stereocilia of hair cells [46,47]. Yoshimura et al. [47] found better hearing preservation scores in patients who had pathogenic variants in the CDH23, MYO7A, or MYO15A gene. The authors speculated that the stereocilia function was the key component in residual hearing, and that CI insertion may not affect the residual function of hair cells. However, in the Korean cohort, no significant differences in hearing preservation rates were noted among recipients with genetic variants expressed mainly in the hair cells (MYO7A, MYO15A, PTPRQ, TMC1, and LOXHD1) and those expressed mainly elsewhere in the cochlea (SLC26A4, GSDME, and TMPRSS3) [46]. This issue merits further investigation in larger cohorts.

INFLUENCE OF COCHLEAR PARAMETERS ON CI

Successful CI surgery requires coverage of the optimal frequency range for a good audiological outcome, while avoiding insertion trauma. To achieve a good audiological outcome, closer positioning of the electrodes to the modiolus and robust scala tympani insertion are essential, while the depth of insertion is the most significant factor for the lateral wall arrays [101,102]. Intracochlear positioning of the electrode array nearer to the modiolus leads to better hearing outcomes for CI recipients implanted with a perimodiolar electrode [48], forming the basis for the pull-back maneuver, which has been introduced for slim modiolar electrodes to ensure better modiolar proximity [49].
Cochlear duct length (CDL) has also been considered as another important factor that influences the intracochlear position of the CI electrode and, therefore, CI outcomes [103]. Understanding the CDL has major implications for the electrode array length selection, adjustment of the angular insertion depth, and frequency mapping [104]. However, the CDL and the cochlear size, shape, and spiral characteristics vary even within normal-hearing individuals according to sex and race [105-107]. Based on this, a concept for individualized CI can be presented to optimize audiological outcomes.
A shorter CDL was noted among subjects with congenital deafness than among those with postlingual onset deafness [10]. Short CDL led to a “relative” over-insertion of slim modiolar electrodes and therefore pushed the electrodes further away from the modiolus towards the lateral wall of the cochlea. For subjects with a short CDL, a further pull-back approach—in which the electrode is pulled back by 1 or 2 mm further than in the conventional pull-back approach—was recommended to compensate for the “relative” over-insertion [10].

CONCLUSION

The precision medicine approach to CI refers to a series of processes that determine and customize the preoperative planning of CI, including the decision of whether to perform CI, the timing of surgery, the position of electrodes during surgery, and the timing of the first switch-on of the device, based on the patient’s genome, imaging information, and even the electrophysiological responses obtained from the patient’s cochlea intraoperatively. Recognizing the relevant genotype-phenotype correlations could provide clinically useful diagnostic and prognostic information. Specifically, genetic information may aid in addressing clinical questions regarding who, how, and when to implant and also in identifying individuals with potentially treatable SNHL, thereby avoiding hasty CI surgery. Identifying the nongenetic causes of hearing loss also impacts CI outcomes. Information gathered from a thorough evaluation of imaging studies can direct the timing of surgery, device selection, and insertion techniques to optimize CI outcomes. For certain types of inner ear malformations, the electrophysiological parameters obtained intraoperatively provide clues to the appropriate positioning of the electrodes, and the timing of the initial switch-on of the device has an important effect on the initial rehabilitation process.

HIGHLIGHTS

▪ The precision medicine approach to cochlear implantation (CI) refers to a series of processes that determine and customize the preoperative planning of CI.
▪ Recognizing relevant genotype-phenotype correlations could provide clinically useful diagnostic and prognostic information.
▪ Information gathered from a thorough evaluation of imaging studies can direct the timing of surgery, device selection, and insertion techniques to maximize CI outcomes.
▪ For certain types of inner ear malformations, the electrophysiological parameters obtained intraoperatively provide clues to the appropriate positioning of the electrodes and the timing of the initial switch-on of the device.

CONFLICT OF INTEREST

Byung Yoon Choi is an Associate Editor of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Notes

Author contributions

Conceptualization: all authors. Funding acquisition: BYC. Methodology: all authors. Project administration: all authors. Writing–original draft: all authors. Writing–review & editing: all authors.

ACKNOWLEDGMENTS

This study was supported by Seoul National University Bundang Hospital intramural research fund (SNUBH-13-2022-0010 to Byung Yoon Choi). This study was also supported by the Basic Science Research Program through the NRF, funded by the Ministry of Education (Grant 2021R1A2C2092038 to Byung Yoon Choi).

Table 1.
Summary of the precision medicine approach to cochlear implantation
Type of hearing loss Testing modality Parameter Implication Reference
Prelingual deafness Genetic testing GJB2, SLC26A4 Excellent results only when implantation is performed before the age of 3.5 years [13,14]
Excellent results even from late implantees [12]
OTOF Consistent benefits when implanted at an appropriate age [15]
Narrow sensitive period for good CI outcomes [12,16-18]
Relatively poorer outcomes and anomalous P1 recovery in CAEP when implantation is performed after 2 years of age than before 2 years of age [12,17]
More rapid catchup in speech abilities when implantation is performed before the age of 18 months [19]
PCDH15 variants and p.G292R of DFNB59 Poor CI outcomes [13]
Identification of genetic etiology Better speech outcome than in cases without an identified genetic etiology [6,7,12]
Imaging study (MRI) Cochlear nerve deficiency Not a contraindication to CI and successful CI outcomes [24]
Require higher stimulation levels than those required by those with normal cochlear nerve dimensions [25-27]
Proper device choice, such as modiolar hugging electrodes with better modiolar proximity, and better initial switch-on strategies ensure earlier stabilization of mapping parameters [28,29]
Common cavity/CADV Electrodes should be inserted in a way that enables maximum contact of the CI electrode with the inner wall of the cavity. [30,31]
Intraoperative ECAP-based positioning of full-band straight electrodes for optimal electrode positioning [30]
cCMV deafness PCR, culture High cCMV titer and culture positivity A wide spectrum of CI outcomes (64% of implantees recognize open-set words after 4 years of use) [21]
Imaging study (MRI) Brain abnormalities Poor prognostic outcomes after CI [20,22]
Normal or partial white matter abnormality Good speech outcomes [23]
Postlingual deafness Genetic testing COCH variants Satisfactory CI results [33]
MYH9 variants Safe and effective in most CI implantees [34]
Variants in MYO15A, TECTA, TMPRSS3, ACTG1 Relatively good CI auditory performance [11]
Identification of causative variants Identification of causative variants lead to better CI outcomes. The duration of deafness is negatively associated with CI outcomes in subjects with identified causative variants. [8]
Causative gene expression site CI outcomes are related to the gene expression site. [35]
Spiral ganglion neuron health CI outcomes are predicted based on the spiral ganglion neuron health. [32]
Variants in COCH, TMPRSS3, NF2 Even subjects with spiral ganglion neuron-related deafness genes can attain some extent of audiological benefit from CI. [33,36,37]
Variants in membranous labyrinth-related deafness genes Favorable CI outcomes [8]
Postlingual auditory neuropathy spectrum disorder Genetic testing Gene expression in the inner hair cell themselves and surrounding supporting cells Favorable outcomes are expected. [38]
TMEM43 variant Successful outcomes have been reported. [40]
Gene expression in the inner hair cell-afferent dendrite junction Favorable outcomes are expected. [39,40]
Gene expression in regions more central to the synaptic junctions Outcomes are unpredictable. No reference
Variants in ATP1A3 and OPA1 Satisfactory outcomes have been reported even though these genes are expressed in the spiral ganglion neurons, as well as in the nerve endings. [42,43]
Potentially treatable deafness Genetic testing NLRP3 variants A lesser degree of cochlear autoinflammation can be amenable to anakinra. Some CI candidates with NLRP3 variants show improvements of hearing loss to a level that can be rehabilitated with conventional hearing aids. [44]
Ski-slope type hearing loss Genetic testing TMPRSS3 variants Early CI is recommended. [45]
Variants in CDH23, MYO7A, MYO15A Better hearing preservation in CI surgery [47]
Variants in certain genes No significant differences in hearing preservation rates between variants of MYO7A, MYO15A, PTPRQ, TMC1, and LOXHD1 and those of SLC26A4, GSDME, and TMPRSS3 [46]
All types of hearing loss X-ray Modiolar proximity Better modiolar proximity leads to better hearing outcomes for CI recipients implanted with a perimodiolar electrode. [48]
Pull-back maneuver (+) Better modiolar proximity is ensured by the intraoperative “pull-back maneuver.” [49]

CI, cochlear implantation; CAEP, cortical auditory evoked potentials; MRI, magnetic resonance imaging; CADV, cochlear aplasia with dilated vestibule; ECAP, electrically evoked compound action potential; PCR, polymerase chain reaction; cCMV, congenital cytomegalovirus.

REFERENCES

1. Tomblin JB, Spencer L, Flock S, Tyler R, Gantz B. A comparison of language achievement in children with cochlear implants and children using hearing aids. J Speech Lang Hear Res. 1999 Apr;42(2):497–509.
crossref pmid
2. Blamey P, Artieres F, Baskent D, Bergeron F, Beynon A, Burke E, et al. Factors affecting auditory performance of postlinguistically deaf adults using cochlear implants: an update with 2251 patients. Audiol Neurootol. 2013 18(1):36–47.
crossref pmid pdf
3. Moberly AC, Bates C, Harris MS, Pisoni DB. The enigma of poor performance by adults with cochlear implants. Otol Neurotol. 2016 Dec;37(10):1522–8.
crossref pmid pmc
4. Archbold SM, Nikolopoulos TP, Lloyd-Richmond H. Long-term use of cochlear implant systems in paediatric recipients and factors contributing to non-use. Cochlear Implants Int. 2009 Mar;10(1):25–40.
crossref pmid
5. Raine CH, Summerfield Q, Strachan DR, Martin JM, Totten C. The cost and analysis of nonuse of cochlear implants. Otol Neurotol. 2008 Feb;29(2):221–4.
crossref pmid
6. Lee CY, Lin PH, Tsai CY, Chiang YT, Chiou HP, Chiang KY, et al. Comprehensive etiologic analyses in pediatric cochlear implantees and the clinical implications. Biomedicines. 2022 Jul;10(8):1846.
crossref pmid pmc
7. Nishio SY, Moteki H, Miyagawa M, Yamasoba T, Kashio A, Iwasaki S, et al. Etiology of hearing loss affects auditory skill development and vocabulary development in pediatric cochlear implantation cases. Acta Otolaryngol. 2022 Mar-Apr;142(3-4):308–15.
crossref pmid
8. Lee SY, Shim YJ, Han JH, Song JJ, Koo JW, Oh SH, et al. The molecular etiology of deafness and auditory performance in the postlingually deafened cochlear implantees. Sci Rep. 2020 Apr;10(1):5768.
crossref pmid pmc pdf
9. Rak K, Ilgen L, Taeger J, Schendzielorz P, Voelker J, Kaulitz S, et al. Influence of cochlear parameters on the current practice in cochlear implantation: development of a concept for personalized medicine. HNO. 2021 Jan;69(Suppl 1):24–30.
crossref pmid pdf
10. Lee SY, Bae YJ, Carandang M, Kim Y, Han JH, Huh G, et al. Influence of cochlear parameters on the current practice in cochlear implantation: development of a concept for personalized medicine. Ear Hear. 2021 Mar/Apr;42(2):323–33.
pmid
11. Miyagawa M, Nishio SY, Ikeda T, Fukushima K, Usami S. Massively parallel DNA sequencing successfully identifies new causative mutations in deafness genes in patients with cochlear implantation and EAS. PLoS One. 2013 Oct;8(10):e75793.
crossref pmid pmc
12. Park JH, Kim AR, Han JH, Kim SD, Kim SH, Koo JW, et al. Outcome of cochlear implantation in prelingually deafened children according to molecular genetic etiology. Ear Hear. 2017 Sep/Oct;38(5):e316–24.
crossref pmid
13. Wu CC, Lin YH, Liu TC, Lin KN, Yang WS, Hsu CJ, et al. Identifying children with poor cochlear implantation outcomes using massively parallel sequencing. Medicine (Baltimore). 2015 Jul;94(27):e1073.
crossref pmid pmc
14. Wu CM, Ko HC, Tsou YT, Lin YH, Lin JL, Chen CK, et al. Long-term cochlear implant outcomes in children with GJB2 and SLC26A4 mutations. PLoS One. 2015 Sep;10(9):e0138575.
crossref pmid pmc
15. Rodriguez-Ballesteros M, del Castillo FJ, Martin Y, Moreno-Pelayo MA, Morera C, Prieto F, et al. Auditory neuropathy in patients carrying mutations in the otoferlin gene (OTOF). Hum Mutat. 2003 Dec;22(6):451–6.
crossref pmid
16. Sharma A, Cardon G. Cortical development and neuroplasticity in auditory neuropathy spectrum disorder. Hear Res. 2015 Dec;330(Pt B):221–32.
crossref pmid pmc
17. Lee SY, Han JH, Song HK, Kim NJ, Yi N, Kyong JS, et al. Central auditory maturation and behavioral outcomes after cochlear implantation in prelingual auditory neuropathy spectrum disorder related to OTOF variants (DFNB9): lessons from pilot study. PLoS One. 2021 Jun;16(6):e0252717.
crossref pmid pmc
18. Liu Y, Dong R, Li Y, Xu T, Li Y, Chen X, et al. Effect of age at cochlear implantation on auditory and speech development of children with auditory neuropathy spectrum disorder. Auris Nasus Larynx. 2014 Dec;41(6):502–6.
crossref pmid
19. Kim BJ, Jang JH, Han JH, Park HR, Oh DY, Lee S, et al. Mutational and phenotypic spectrum of OTOF-related auditory neuropathy in Koreans: eliciting reciprocal interaction between bench and clinics. J Transl Med. 2018 Nov;16(1):330.
crossref pmid pmc pdf
20. Philips B, Maes LK, Keppler H, Dhooge I. Cochlear implants in children deafened by congenital cytomegalovirus and matched Connexin 26 peers. Int J Pediatr Otorhinolaryngol. 2014 Mar;78(3):410–5.
crossref pmid
21. Lee DJ, Lustig L, Sampson M, Chinnici J, Niparko JK. Effects of cytomegalovirus (CMV) related deafness on pediatric cochlear implant outcomes. Otolaryngol Head Neck Surg. 2005 Dec;133(6):900–5.
crossref pmid pdf
22. Laccourreye L, Ettienne V, Prang I, Couloigner V, Garabedian EN, Loundon N. Speech perception, production and intelligibility in French-speaking children with profound hearing loss and early cochlear implantation after congenital cytomegalovirus infection. Eur Ann Otorhinolaryngol Head Neck Dis. 2015 Dec;132(6):317–20.
crossref pmid
23. Han JJ, Bae YJ, Song SK, Song JJ, Koo JW, Lee JH, et al. Prediction of the outcome of cochlear implantation in the patients with congenital cytomegalovirus infection based on magnetic resonance imaging characteristics. J Clin Med. 2019 Jan;8(2):136.
crossref pmid pmc
24. Vlastarakos PV, Nikolopoulos TP, Pappas S, Buchanan MA, Bewick J, Kandiloros D. Cochlear implantation update: contemporary preoperative imaging and future prospects: the dual modality approach as a standard of care. Expert Rev Med Devices. 2010 Jul;7(4):555–67.
crossref pmid
25. Yousef M, Mesallam TA, Garadat SN, Almasaad A, Alzhrani F, Alsanosi A, et al. Audiologic outcome of cochlear implantation in children with cochlear nerve deficiency. Otol Neurotol. 2021 Jan;42(1):38–46.
crossref pmid
26. Valero J, Blaser S, Papsin BC, James AL, Gordon KA. Electrophysiologic and behavioral outcomes of cochlear implantation in children with auditory nerve hypoplasia. Ear Hear. 2012 Jan-Feb;33(1):3–18.
crossref pmid
27. Incerti PV, Ching TY, Hou S, Van Buynder P, Flynn C, Cowan R. Programming characteristics of cochlear implants in children: effects of aetiology and age at implantation. Int J Audiol. 2018 May;57(sup2):S27–40.
crossref pmid
28. Sunwoo W, Jeon HW, Choi BY. Effect of initial switch-on within 24 hours of cochlear implantation using slim modiolar electrodes. Sci Rep. 2021 Nov;11(1):22809.
crossref pmid pmc pdf
29. Kim Y, Kim Y, Kim YS, Lee SY, Choi BY. Tight modiolar proximity and feasibility of slim modiolar cochlear implant electrode array insertion in diverse etiologies of hearing loss. Eur Arch Otorhinolaryngol. 2022 Aug;279(8):3899–909.
crossref pmid pdf
30. Lee SY, Choi BY. Potential implications of slim modiolar electrodes for severely malformed cochleae: a comparison with the straight array with circumferential electrodes. Clin Exp Otorhinolaryngol. 2021 Aug;14(3):287–94.
crossref pmid pmc pdf
31. Bae SH, Choi J, Choi JY. Cochlear implants for patients with common cavity deformities and the impact of electrode positioning. Clin Exp Otorhinolaryngol. 2022 Feb;15(1):77–83.
crossref pmid pmc pdf
32. Shearer AE, Eppsteiner RW, Frees K, Tejani V, Sloan-Heggen CM, Brown C, et al. Genetic variants in the peripheral auditory system significantly affect adult cochlear implant performance. Hear Res. 2017 May;348:138–42.
crossref pmid pmc
33. Vermeire K, Brokx JP, Wuyts FL, Cochet E, Hofkens A, De Bodt M, et al. Good speech recognition and quality-of-life scores after cochlear implantation in patients with DFNA9. Otol Neurotol. 2006 Jan;27(1):44–9.
crossref pmid
34. Pecci A, Verver EJ, Schlegel N, Canzi P, Boccio CM, Platokouki H, et al. Cochlear implantation is safe and effective in patients with MYH9-related disease. Orphanet J Rare Dis. 2014 Jun;9:100.
crossref pmid pmc
35. Eppsteiner RW, Shearer AE, Hildebrand MS, Deluca AP, Ji H, Dunn CC, et al. Prediction of cochlear implant performance by genetic mutation: the spiral ganglion hypothesis. Hear Res. 2012 Oct;292(1-2):51–8.
crossref pmid pmc
36. Miyagawa M, Nishio SY, Sakurai Y, Hattori M, Tsukada K, Moteki H, et al. The patients associated with TMPRSS3 mutations are good candidates for electric acoustic stimulation. Ann Otol Rhinol Laryngol. 2015 May;124 Suppl 1:193S–204S.
crossref pmid pdf
37. Tolisano AM, Baumgart B, Whitson J, Kutz JW. Cochlear implantation in patients with neurofibromatosis type 2. Otol Neurotol. 2019 Apr;40(4):e381–5.
crossref pmid
38. Kim TB, Isaacson B, Sivakumaran TA, Starr A, Keats BJ, Lesperance MM. A gene responsible for autosomal dominant auditory neuropathy (AUNA1) maps to 13q14-21. J Med Genet. 2004 Nov;41(11):872–6.
crossref pmid pmc
39. Ruel J, Emery S, Nouvian R, Bersot T, Amilhon B, Van Rybroek JM, et al. Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice. Am J Hum Genet. 2008 Aug;83(2):278–92.
crossref pmid pmc
40. Chen DY, Liu XF, Lin XJ, Zhang D, Chai YC, Yu DH, et al. A dominant variant in DMXL2 is linked to nonsyndromic hearing loss. Genet Med. 2017 May;19(5):553–8.
crossref pmid pdf
41. Jang MW, Oh DY, Yi E, Liu X, Ling J, Kim N, et al. Nonsense TMEM43 variant leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder. Proc Natl Acad Sci U S A. 2021 Jun;118(22):e2019681118.
pmid pmc
42. Han KH, Oh DY, Lee S, Lee C, Han JH, Kim MY, et al. ATP1A3 mutations can cause progressive auditory neuropathy: a new gene of auditory synaptopathy. Sci Rep. 2017 Nov;7(1):16504.
crossref pmid pmc pdf
43. Santarelli R, Rossi R, Scimemi P, Cama E, Valentino ML, La Morgia C, et al. OPA1-related auditory neuropathy: site of lesion and outcome of cochlear implantation. Brain. 2015 Mar;138(Pt 3):563–76.
crossref pmid pmc
44. Kim BJ, Kim YH, Han JH, Lee SY, Carandang M, Lee DH, et al. Outcome of cochlear implantation in NLRP3-related autoinflammatory inner ear disorders. Otol Neurotol. 2021 Feb;42(2):e168–71.
crossref pmid
45. Holder JT, Morrel W, Rivas A, Labadie RF, Gifford RH. Cochlear implantation and electric acoustic stimulation in children with TMPRSS3 genetic mutation. Otol Neurotol. 2021 Mar;42(3):396–401.
crossref pmid pmc
46. Kim Y, Han JH, Yoo HS, Choi BY. Molecular aetiology of ski-slope hearing loss and audiological course of cochlear implantees. Eur Arch Otorhinolaryngol. 2022 Oct;279(10):4871–82.
crossref pmid pdf
47. Yoshimura H, Moteki H, Nishio SY, Miyajima H, Miyagawa M, Usami SI. Genetic testing has the potential to impact hearing preservation following cochlear implantation. Acta Otolaryngol. 2020 Jun;140(6):438–44.
crossref pmid
48. Ramos de Miguel A, Durmo I, Falcon Gonzalez JC, Borkoski Barreiro S, Ramos Macias A. Evaluation of intracochlear position of a slim modiolar electrode array, by using different radiological analyses. Otol Neurotol. 2019 Jun;40(5S Suppl 1):S10–7.
crossref pmid
49. Riemann C, Sudhoff H, Todt I. The pull-back technique for the 532 slim modiolar electrode. Biomed Res Int. 2019 May;2019:6917084.
crossref pmid pmc pdf
50. Shearer AE, DeLuca AP, Hildebrand MS, Taylor KR, Gurrola J 2nd, Scherer S, et al. Comprehensive genetic testing for hereditary hearing loss using massively parallel sequencing. Proc Natl Acad Sci U S A. 2010 Dec;107(49):21104–9.
crossref pmid pmc
51. Brownstein Z, Friedman LM, Shahin H, Oron-Karni V, Kol N, Abu Rayyan A, et al. Targeted genomic capture and massively parallel sequencing to identify genes for hereditary hearing loss in Middle Eastern families. Genome Biol. 2011 Sep;14;12(9):R89.
crossref pmid pmc
52. Black J, Hickson L, Black B, Perry C. Prognostic indicators in paediatric cochlear implant surgery: a systematic literature review. Cochlear Implants Int. 2011 May;12(2):67–93.
crossref pmid
53. Park JH, Kim NK, Kim AR, Rhee J, Oh SH, Koo JW, et al. Exploration of molecular genetic etiology for Korean cochlear implantees with severe to profound hearing loss and its implication. Orphanet J Rare Dis. 2014 Nov;9:167.
crossref pmid pmc pdf
54. Wu CC, Lee YC, Chen PJ, Hsu CJ. Predominance of genetic diagnosis and imaging results as predictors in determining the speech perception performance outcome after cochlear implantation in children. Arch Pediatr Adolesc Med. 2008 Mar;162(3):269–76.
crossref pmid
55. Yan YJ, Li Y, Yang T, Huang Q, Wu H. The effect of GJB2 and SLC26A4 gene mutations on rehabilitative outcomes in pediatric cochlear implant patients. Eur Arch Otorhinolaryngol. 2013 Nov;270(11):2865–70.
crossref pmid pdf
56. Yoshida H, Takahashi H, Kanda Y, Usami S. Long term speech perception after cochlear implant in pediatric patients with GJB2 mutations. Auris Nasus Larynx. 2013 Oct;40(5):435–9.
crossref pmid
57. Delmaghani S, Defourny J, Aghaie A, Beurg M, Dulon D, Thelen N, et al. Hypervulnerability to sound exposure through impaired adaptive proliferation of peroxisomes. Cell. 2015 Nov;163(4):894–906.
crossref pmid
58. Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol. 2007 Jul-Aug;17(4):253–76.
crossref pmid
59. Manicklal S, Emery VC, Lazzarotto T, Boppana SB, Gupta RK. The “silent” global burden of congenital cytomegalovirus. Clin Microbiol Rev. 2013 Jan;26(1):86–102.
crossref pmid pmc pdf
60. Fowler KB, Boppana SB. Congenital cytomegalovirus (CMV) infection and hearing deficit. J Clin Virol. 2006 Feb;35(2):226–31.
crossref pmid
61. Stagno S, Pass RF, Cloud G, Britt WJ, Henderson RE, Walton PD, et al. Primary cytomegalovirus infection in pregnancy: incidence, transmission to fetus, and clinical outcome. JAMA. 1986 Oct;256(14):1904–8.
crossref pmid
62. Goderis J, De Leenheer E, Smets K, Van Hoecke H, Keymeulen A, Dhooge I. Hearing loss and congenital CMV infection: a systematic review. Pediatrics. 2014 Nov;134(5):972–82.
crossref pmid pdf
63. Goderis J, Keymeulen A, Smets K, Van Hoecke H, De Leenheer E, Boudewyns A, et al. Hearing in children with congenital cytomegalovirus infection: results of a longitudinal study. J Pediatr. 2016 May;172:110–5. e2.
crossref pmid
64. Medearis DN. Viral infections during pregnancy and abnormal human development. Am J Obstet Gynecol. 1964 Dec;90(7):1140–8.
crossref
65. Kim BJ, Han JJ, Shin SH, Kim HS, Yang HR, Choi EH, et al. Characterization of detailed audiological features of cytomegalovirus infection: a composite cohort study from groups with distinct demographics. Biomed Res Int. 2018 Aug;2018:7087586.
crossref pmid pmc pdf
66. Sohn YM, Park KI, Lee C, Han DG, Lee WY. Congenital cytomegalovirus infection in Korean population with very high prevalence of maternal immunity. J Korean Med Sci. 1992 Mar;7(1):47–51.
crossref pmid pmc
67. Barkai G, Ari-Even Roth D, Barzilai A, Tepperberg-Oikawa M, Mendelson E, Hildesheimer M, et al. Universal neonatal cytomegalovirus screening using saliva: report of clinical experience. J Clin Virol. 2014 Aug;60(4):361–6.
crossref pmid
68. Ramirez Inscoe JM, Nikolopoulos TP. Cochlear implantation in children deafened by cytomegalovirus: speech perception and speech intelligibility outcomes. Otol Neurotol. 2004 Jul;25(4):479–82.
crossref pmid
69. Iwasaki S, Nakanishi H, Misawa K, Tanigawa T, Mizuta K. Cochlear implant in children with asymptomatic congenital cytomegalovirus infection. Audiol Neurootol. 2009 14(3):146–52.
crossref pmid pdf
70. Matsui T, Ogawa H, Yamada N, Baba Y, Suzuki Y, Nomoto M, et al. Outcome of cochlear implantation in children with congenital cytomegalovirus infection or GJB2 mutation. Acta Otolaryngol. 2012 Jun;132(6):597–602.
crossref pmid
71. Ciorba A, Bovo R, Trevisi P, Bianchini C, Arboretti R, Martini A. Rehabilitation and outcome of severe profound deafness in a group of 16 infants affected by congenital cytomegalovirus infection. Eur Arch Otorhinolaryngol. 2009 Oct;266(10):1539–46.
crossref pmid pdf
72. Malik V, Bruce IA, Broomfield SJ, Henderson L, Green KM, Ramsden RT. Outcome of cochlear implantation in asymptomatic congenital cytomegalovirus deafened children. Laryngoscope. 2011 Aug;121(8):1780–4.
crossref pmid
73. Viccaro M, Filipo R, Bosco E, Nicastri M, Mancini P. Long-term follow-up of implanted children with cytomegalovirus-related deafness. Audiol Neurootol. 2012 Oct;17(6):395–9.
crossref pmid pdf
74. Casselman JW, Offeciers FE, Govaerts PJ, Kuhweide R, Geldof H, Somers T, et al. Aplasia and hypoplasia of the vestibulocochlear nerve: diagnosis with MR imaging. Radiology. 1997 Mar;202(3):773–81.
crossref pmid
75. Glastonbury CM, Davidson HC, Harnsberger HR, Butler J, Kertesz TR, Shelton C. Imaging findings of cochlear nerve deficiency. AJNR Am J Neuroradiol. 2002 Apr;23(4):635–43.
pmid pmc
76. McClay JE, Booth TN, Parry DA, Johnson R, Roland P. Evaluation of pediatric sensorineural hearing loss with magnetic resonance imaging. Arch Otolaryngol Head Neck Surg. 2008 Sep;134(9):945–52.
crossref pmid
77. Birman CS, Powell HR, Gibson WP, Elliott EJ. Cochlear implant outcomes in cochlea nerve aplasia and hypoplasia. Otol Neurotol. 2016 Jun;37(5):438–45.
crossref pmid
78. Ozdogmus O, Sezen O, Kubilay U, Saka E, Duman U, San T, et al. Connections between the facial, vestibular and cochlear nerve bundles within the internal auditory canal. J Anat. 2004 Jul;205(1):65–75.
crossref pmid pmc
79. Thai-Van H, Fraysse B, Berry I, Berges C, Deguine O, Honegger A, et al. Functional magnetic resonance imaging may avoid misdiagnosis of cochleovestibular nerve aplasia in congenital deafness. Am J Otol. 2000 Sep;21(5):663–70.
pmid
80. Acker T, Mathur NN, Savy L, Graham JM. Is there a functioning vestibulocochlear nerve? Cochlear implantation in a child with symmetrical auditory findings but asymmetric imaging. Int J Pediatr Otorhinolaryngol. 2001 Feb;57(2):171–6.
crossref pmid
81. Buchman CA, Teagle HF, Roush PA, Park LR, Hatch D, Woodard J, et al. Cochlear implantation in children with labyrinthine anomalies and cochlear nerve deficiency: implications for auditory brainstem implantation. Laryngoscope. 2011 Sep;121(9):1979–88.
crossref pmid pdf
82. Young NM, Kim FM, Ryan ME, Tournis E, Yaras S. Pediatric cochlear implantation of children with eighth nerve deficiency. Int J Pediatr Otorhinolaryngol. 2012 Oct;76(10):1442–8.
crossref pmid
83. Shelton C, Luxford WM, Tonokawa LL, Lo WW, House WF. The narrow internal auditory canal in children: a contraindication to cochlear implants. Otolaryngol Head Neck Surg. 1989 Mar;100(3):227–31.
crossref pmid pdf
84. Brotto D, Avato I, Lovo E, Muraro E, Bovo R, Trevisi P, et al. Epidemiologic, imaging, audiologic, clinical, surgical, and prognostic issues in common cavity deformity: a narrative review. JAMA Otolaryngol Head Neck Surg. 2019 Jan;145(1):72–8.
crossref pmid
85. Kim BJ, Choi BY. How to maximize the outcomes of cochlear implantation in common cavity and cochlear aplasia with dilated vestibule, the most severe inner ear anomalies. Clin Exp Otorhinolaryngol. 2022 Feb;15(1):3–4.
crossref pmid pmc pdf
86. Alhabib SF. Audiological and speech performance after cochlear implantation in cochlear aplasia deformity. Cureus. 2021 Jul;13(7):e16654.
crossref pmid pmc
87. Jeong SW, Kim LS. Cochlear implantation in children with cochlear aplasia. Acta Otolaryngol. 2012 Sep;132(9):910–5.
crossref pmid
88. Graham JM, Phelps PD, Michaels L. Congenital malformations of the ear and cochlear implantation in children: review and temporal bone report of common cavity. J Laryngol Otol Suppl. 2000 Mar;114(S25):1–14.
crossref
89. Yamazaki H, Naito Y, Fujiwara K, Moroto S, Yamamoto R, Yamazaki T, et al. Electrically evoked auditory brainstem response-based evaluation of the spatial distribution of auditory neuronal tissue in common cavity deformities. Otol Neurotol. 2014 Sep;35(8):1394–402.
crossref pmid
90. Wei X, Zhang H, Lu S, Yang M, Chen B, Chen J, et al. Application of multiplanar volume reconstruction technique for the assessment of electrode location and analysis of the correlation to cochlear programming and performance in common cavity deformity. Front Neurol. 2022 Jan;12:783225.
crossref pmid pmc
91. Miyagawa M, Nishio SY, Usami S. A comprehensive study on the etiology of patients receiving cochlear implantation with special emphasis on genetic epidemiology. Otol Neurotol. 2016 Feb;37(2):e126–34.
crossref pmid pmc
92. Michalski N, Petit C. Genes involved in the development and physiology of both the peripheral and central auditory systems. Annu Rev Neurosci. 2019 Jul;42:67–86.
crossref pmid
93. Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J. NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorder. Immunity. 2004 Mar;20(3):319–25.
crossref pmid
94. Kim YH, Kim BJ, Han J, Choi BY, Lee S. Long-term efficacy of anakinra in cryopyrin-associated periodic syndrome: focus on destructive arthropathy. J Clin Immunol. 2021 Nov;41(8):1936–9.
crossref pmid pdf
95. Kim BJ, Kim YH, Lee S, Han JH, Lee SY, Seong J, et al. Otological aspects of NLRP3-related autoinflammatory disorder focusing on the responsiveness to anakinra. Rheumatology (Oxford). 2021 Mar;60(3):1523–32.
crossref pmid pdf
96. Choi BY, Park G, Gim J, Kim AR, Kim BJ, Kim HS, et al. Diagnostic application of targeted resequencing for familial nonsyndromic hearing loss. PLoS One. 2013 Aug;8(8):e68692.
crossref pmid pmc
97. Shearer AE, Hildebrand MS, Smith RJ. Hereditary hearing loss and deafness overview. Seattle (WA): University of Washington, Seattle; 2017.

98. Roland JT, Gantz BJ, Waltzman SB, Parkinson AJ. Long-term outcomes of cochlear implantation in patients with high-frequency hearing loss. Laryngoscope. 2018 Aug;128(8):1939–45.
crossref pmid pmc pdf
99. Shew MA, Walia A, Durakovic N, Valenzuela C, Wick CC, McJunkin JL, et al. Long-term hearing preservation and speech perception performance outcomes with the slim modiolar electrode. Otol Neurotol. 2021 Dec;42(10):e1486–93.
crossref pmid
100. Haber K, Neagu A, Konopka W, Amernik K, Gheorghe DC, Drela M, et al. The influence of slim modiolar electrode on residual hearing in pediatric patients. Eur Arch Otorhinolaryngol. 2021 Aug;278(8):2723–32.
crossref pmid pdf
101. O’Connell BP, Hunter JB, Haynes DS, Holder JT, Dedmon MM, Noble JH, et al. Insertion depth impacts speech perception and hearing preservation for lateral wall electrodes. Laryngoscope. 2017 Oct;127(10):2352–7.
crossref pmid pmc pdf
102. Chakravorti S, Noble JH, Gifford RH, Dawant BM, O’Connell BP, Wang J, et al. Further evidence of the relationship between cochlear implant electrode positioning and hearing outcomes. Otol Neurotol. 2019 Jun;40(5):617–24.
crossref pmid pmc
103. Dhanasingh A, Jolly C. An overview of cochlear implant electrode array designs. Hear Res. 2017 Dec;356:93–103.
crossref pmid
104. Dhanasingh A. Cochlear duct length along the outer wall vs organ of corti: which one is relevant for the electrode array length selection and frequency mapping using Greenwood function. World J Otorhinolaryngol Head Neck Surg. 2018 Dec;5(2):117–21.
crossref pmid pmc pdf
105. Escude B, James C, Deguine O, Cochard N, Eter E, Fraysse B. The size of the cochlea and predictions of insertion depth angles for cochlear implant electrodes. Audiol Neurootol. 2006 11 Suppl 1:27–33.
pmid
106. Zahara D, Dewi RD, Aboet A, Putranto FM, Lubis ND, Ashar T. Variations in cochlear size of cochlear implant candidates. Int Arch Otorhinolaryngol. 2019 Apr;23(2):184–90.
crossref pmid
107. Grover M, Sharma S, Singh SN, Kataria T, Lakhawat RS, Sharma MP. Measuring cochlear duct length in Asian population: worth giving a thought! Eur Arch Otorhinolaryngol. 2018 Mar;275(3):725–8.
crossref pmid pdf
Editorial Office
Korean Society of Otorhinolaryngology-Head and Neck Surgery
103-307 Park Tower officetel, Yongsan-dong 5-ga, Yongsan-gu, Seoul 04385, Korea
TEL: +82-2-711-9091   FAX: +82-2-3487-6603   E-mail: editor.eceo@gmail.com
Copyright © Korean Society of Otorhinolaryngology-Head and Neck Surgery.                 Developed in M2PI
Close layer
prev next