An Unusual and Discrepant Presentation of a Skull Base Paraganglioma.

Paragangliomas are rare tumors of neuroendocrine origin. Within the head and neck, these tumors are slow-growing and locally destructive, with a small malignant potential. Vagal paragangliomas (VPs) originate from paraganglia around the vagus nerve, typically at the level of the skull base. Cranial nerve deficits are common at presentation, with the vagus nerve and hypoglossal nerves being most affected. Similarly, hypoglossal paragangliomas (HPs) originate from around the hypoglossal nerve but are extremely rare and less documented. We describe the case of a patient presenting with an isolated hypoglossal nerve palsy in the setting of a tumor that radiologically represents a VP. A descriptive literature review was conducted to highlight presentation, management, and outcomes related to this pathology. A 65-year-old male presented to the clinic with tongue fasciculations and several years of dysarthria. Physical examination showed intermittent right tongue fasciculations in addition to ipsilateral hemi-atrophy. A computed tomography scan with contrast revealed an enhancing skull base mass inferior to the right carotid space. Subsequently, magnetic resonance imaging with contrast further delineated its anatomic involvement and site of origin, allowing for the diagnosis of a VP. After further discussion with the patient about his clinical findings, the decision was made to proceed with observation and serial imaging. Skull base paragangliomas are a rare pathologic entity that may pose a challenging multidisciplinary approach to optimize management strategies. Treatment may vary on a case-by-case basis and is dependent on patient and tumor characteristics.

Reduction of Antibiotic-Associated Conditions After Tympanostomy Tube Placement in Children.

OBJECTIVE: Tympanostomy tube placement has been shown to decrease systemic antibiotics usage in patients with recurrent acute otitis media. Systemic antibiotics in children are associated with an increase in antibiotic-associated conditions (asthma, allergic rhinitis, food allergy, atopic dermatitis, celiac disease, overweight/obesity, attention-deficit hyperactivity disorder [ADHD], autism, learning disability, and Clostridium difficile colonization) later in life. The objective of this study is to estimate whether tympanostomy tube placement is associated with a reduction in antibiotic-associated conditions in children with recurrent acute otitis media (RAOM). METHODS: A retrospective cohort review of electronic medical records from 1991 to 2011 at a large pediatric hospital system was performed identifying 27,584 patients under 18 years old with RAOM, defined by 3 or more episodes of AOM. Antibiotic-associated conditions were defined using ICD-9 and ICD-10 codes. RESULTS: The enrollment population was largely composed of White patients (28.9%), Black patients (30.1%), and Hispanic/Latino patients (16.4%). The number of systemic antibiotics prescribed per encounter was significantly lower in children who pursued tympanostomy tubes (0.14 antibiotics per encounter) versus those who did not (0.23 antibiotics per encounter) (p < 0.001). Patients with RAOM who received tympanostomy tubes were less likely to have diagnoses of overweight/obesity (OR. 0.62 [0.55, 0.68]; p < 0.001), asthma (OR 0.8 [0.74, 0.87]; p < 0.001), allergic rhinitis (OR 0.72 [0.65, 0.81]; p < 0.001), and atopic dermatitis (0.78 [0.71, 0.86]; p < 0.001). CONCLUSIONS AND RELEVANCE: Tympanostomy tube placement is associated with less systemic antibiotic administration and a decreased incidence of overweight/obesity, asthma, allergic rhinitis, and atopic dermatitis in children diagnosed with RAOM. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Cochlear implantation in patients with inner ear schwannomas: a systematic review and meta-analysis of audiological outcomes.

PURPOSE: In patients with inner ear schwannomas (IES), reports on hearing rehabilitation with cochlear implants (CI) have increased over the past decade, most of which are case reports or small case series. The aim of this study is to systematically review the reported hearing results with CI in patients with IES considering the different audiologic outcome measures used in different countries. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, a search of published literature was conducted. We included patients with IES (primary or with secondary extension from the internal auditory canal (IAC) to the inner ear, sporadic or NF2 related) undergoing cochlear implantation with or without tumour removal. The audiological results were divided into the categories "monosyllables", "disyllables", "multisyllabic words or numbers", and "sentences". RESULTS: Predefined audiological outcome measures were available from 110 patients and 111 ears in 27 reports. The mean recognition scores for monosyllabic words with CI were 55% (SD: 24), for bisyllabic words 61% (SD: 36), for multisyllabic words and numbers 87% (SD: 25), and 71% (SD: 30) for sentences. Results from for multisyllabic words and numbers in general showed a tendency towards a ceiling effect. Possible risk factors for performance below average were higher complexity tumours (inner ear plus IAC/CPA), NF2, CI without tumour removal ("CI through tumour"), and sequential cochlear implantation after tumour removal (staged surgery). CONCLUSION: Hearing loss in patients with inner ear schwannomas can be successfully rehabilitated with CI with above average speech performance in most cases. Cochlear implantation thus represents a valuable option for hearing rehabilitation also in patients with IES while at the same time maintaining the possibility of MRI follow-up. Further studies should investigate possible risk factors for poor performance. Audiological tests and outcome parameters should be reported in detail and ideally be harmonized to allow better comparison between languages.

Sensorineural hearing loss among type 2 diabetic patients and its association with peripheral neuropathy: a cross-sectional study from a lower middle-income country.

INTRODUCTION: Despite potential links between diabetes and sensorineural hearing loss (SNHL), routine hearing assessments for diabetic patients are not standard practice. Our study aimed to investigate the prevalence of SNHL and its association with diabetes-related factors among patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: This cross-sectional study was conducted at the Diabetes Clinic, Jinnah Postgraduate Medical Centre, Karachi, Pakistan, from May to September 2021. A total of 396 patients fulfilling the inclusion criteria participated after informed consent. Data collection involved a sociodemographic profile, Michigan Neuropathy Screening Instrument examination followed by pure-tone audiometry and laboratory tests including haemoglobin A1C (HbA1c). HL was defined using better ear four-frequency pure-tone average of ≥26 dB HL and graded as per WHO criteria. Statistical analyses were performed using SPSS. χ2, independent t-test and multinomial logistic regression analyses were applied. P<0.05 at 95% CI was considered significant. RESULTS: Our study revealed a high prevalence of SNHL among patients with T2DM. Mild HL was seen in 55.8%, while 18.7% suffered from moderate HL. Common audiological symptoms included difficulty understanding speech in noisy surroundings (44.2%), balance problems (42.9%), sentence repetition (35.9%), tinnitus (32.3%) and differentiating consonants (31.1%). Hearing impairment predominantly affected low (0.25-0.5 kHz) and high (4-8 kHz) frequencies with a significant difference at 4 kHz among both sexes (t (394)=2.8, p=0.004). Peripheral neuropathy was significantly associated with SNHL on multinomial logistic regression after adjusting with age, sex, body mass index and the presence of any comorbidities. Diabetes duration, HbA1c or family history of diabetes was found unrelated to SNHL severity. CONCLUSIONS: The study highlights the substantial prevalence of SNHL among patients with T2DM and emphasises the importance of targeted audiological care as part of a holistic approach to diabetes management. Addressing HL early may significantly improve communication and overall quality of life.

Importance of preoperative HRCT temporal bone in the orientation of the cochlea and its relation to intra-operative difficulties in cochlear implantation - predicting the grades of difficulty.

OBJECTIVE: This study emphasizes the role of preoperative high-resolution computed tomography (HRCT) temporal bone in evaluating the variation in cochlear orientation and proposes a grading system to determine the level of intraoperative difficulties encountered. METHODS: Preoperative correlation of middle ear and inner ear structures along with the basal turn angle (BTA) was done to assess the orientation. Patients were divided into three groups depending on BTA and radiology findings. RESULTS: Group A (BTA = 55°-60°) had statistically significant (p < 0.05) correlation between middle ear to inner ear structures on HRCT, whereas group B (BTA >60°) and C (BTA <55°) had variations in the alignment of middle ear structures to their corresponding inner ear structures. CONCLUSION: The association of BTA to the correlation between middle ear and inner ear structures can determine the orientation of the cochlea. This evaluation makes the surgeon aware of intraoperative challenges and helps in surgical planning.

[Increased report completeness and satisfaction with structured neurotological reporting in the interdisciplinary assessment of vertigo]. / Erhöhte Befundvollständigkeit und gesteigerte Zuweiserzufriedenheit bei strukturierter neurootologischer Befunderhebung in der interdisziplinären Schwindelabklärung.

BACKGROUND: Results of neurotological function diagnostics in the context of interdisciplinary vertigo assessment are usually formulated as free-text reports (FTR). These are often subject to high variability, which may lead to loss of information. The aim of the present study was to evaluate the completeness of structured reports (SR) and referrer satisfaction in the neurotological assessment of vertigo. MATERIALS AND METHODS: Neurotological function diagnostics performed as referrals (n = 88) were evaluated retrospectively. On the basis of the available raw data, SRs corresponding to FTRs from clinical routine were created by means of a specific SR template for neurotological function diagnostics. FTRs and SRs were evaluated for completeness and referring physician satisfaction (n = 8) using a visual analog scale (VAS) questionnaire. RESULTS: Compared to FTRs, SRs showed significantly increased overall completeness (73.7% vs. 51.7%, p < 0.001), especially in terms of patient history (92.5% vs. 66.7%, p < 0.001), description of previous findings (87.5% vs. 38%, p < 0.001), and neurotological (33.5% vs. 26.7%, p < 0.001) and audiometric function diagnostics (58% vs. 32.3%, p < 0.001). In addition, SR showed significantly increased referring physician satisfaction (VAS 8.8 vs. 4.9, p < 0.001). CONCLUSION: Neurotological SRs enable a significantly increased report completeness with higher referrer satisfaction in the context of interdisciplinary assessment of vertigo. Furthermore, SRs are particularly suitable for scientific data analysis, especially in the context of big data analyses.

Sudden Deafness and Vestibulopathy in a Patient with Antibody Treatment for Metastatic Lung Cancer.

We describe the case of a patient who presented with sudden onset vertigo and bilateral deafness while under immune checkpoint therapy for metastatic bronchial carcinoma. Extensive audiologic assessment and vestibular function testing, as well as cranial magnetic resonance imaging (cMRI) and lumbar puncture was performed. The diagnostic workup confirmed bilateral sensorineural deafness and bilateral loss of vestibular function, while imaging revealed enhancement of the vestibulocochlear nerve. Initially, immunotherapy with PD-L1 antibody atezolizumab was the assumed cause of the described symptoms. However, further findings strengthened the suspicion of meningeosis neoplastica. The differential diagnoses of hearing loss and vestibulopathy in the context of platin-based chemotherapy, checkpoint inhibitor therapy and metastatic disease should be kept in mind for appropriate workup and therapy. Laryngoscope, 2024.

The History of Superior Semicircular Canal Dehiscence: A Bibliometric Analysis.

OBJECTIVE: The treatment and understanding of superior semicircular canal dehiscence (SSCD) has seen significant developments over the past 25 years. Bibliographic analysis can provide insight into the evolution of research as well as highlight emerging areas. Reviewing a large volume of publications provides valuable insights into the citation patterns and collaborations of research groups. This study seeks to offer a comprehensive historical overview of SSCD and leading authors. DATABASE REVIEWED: Web of Science Core Collection. METHODS: A bibliometric analysis of the current literature on SSCD was conducted. A performance analysis and science mapping of the top 100 most cited articles was completed using a citation analysis. Two independent reviewers evaluated articles for relevance and adjugated by a third reviewer. Author and institution networks were examined. RESULTS: Seven hundred ninety-one articles on the topic of SSCD were identified. The top 100 articles spanned over 23 years from 1998 to 2019 and were published in 30 different journals. The top 100 articles were cited 8253 times in literature. The document contents revealed 233 keywords and 238 author keywords. The articles were authored by a total of 291 authors, with only 4 single-authored documents. CONCLUSIONS: SSCD has been highly researched in aspects of symptomatology, diagnosis, and treatment, as indicated by many highly cited articles that relate. However, the production of highly cited articles on SSCD displays a significant decrease after 2013, with only 17 of the top cited articles published since then.

Cognitive and language outcomes for pediatric hearing loss with otologic surgery.

OBJECTIVES: To test the hypothesis that surgical otologic intervention for any type of pediatric hearing loss decreases the odds for incident adverse cognitive and linguistic developmental outcomes. STUDY DESIGN: Retrospective cohort database study. METHODS: Electronic medical record data from the TriNetX Research Network were queried for children with congenital, sensorineural, conductive, and mixed hearing loss (HL) between ages 0 and 5 years. Patients were further stratified by presence (HL + surgery) or absence (HL-surgery) of surgical intervention at any point following diagnosis, including cochlear implantation, tympanoplasty with or without mastoidectomy, and tympanostomy. Primary outcomes were defined as odds for new adverse cognitive or linguistic outcomes at any point given HL treatment status [odds ratio with 95% confidence interval, (OR; 95%CI, p-value)]. Cohorts were balanced using propensity-score matching (PSM) based on US census-defined demographics and clinically relevant congenital conditions. RESULTS: Of 457,636 total patients included in the study, 118,576 underwent surgery (HL + surgery cohort) and 339,060 did not (HL-surgery). In matched cohorts, surgical otologic intervention significantly decreased the odds of developing cognitive disorders including scholastic, motor, psychological developmental disorders, and pervasive developmental delays (p < 0.01). CONCLUSIONS: Surgical interventions for treatment of pediatric HL including cochlear implantation, tympanoplasty with or without mastoidectomy, and tympanostomy should be considered as they may prevent delays in development.

Statistical Associations between Vestibular Pathologies and Hypothyroidism: A Retrospective Study.

The association between vestibular pathologies and thyroid hormone disorders has been known for several decades. However, very little information is available on the types of vestibular symptoms that may be affected by altered thyroid hormone levels. The aim of this study was to provide patient data in order to identify statistical associations between vestibular pathologies and thyroid hormone disorders. A retrospective review of the records of 422 patients seen for physiotherapy treatment of vertigo was carried out. Statistical analysis of the data was performed using logistic regression, providing Chi2 and Odds Ratio statistics. Our results show that hypothyroidism statistically significantly increases the expression of certain symptoms, such as vestibular instability and gait disorders, in vestibular pathologies such as Menière's disease or central vertigo. By analyzing patient data, our study provides new evidence of dependence between altered thyroid status and the expression of vestibular pathologies.

A diagnostic framework to identify vestibular involvement in multi-sensory neurological disease.

BACKGROUND AND PURPOSE: Identifying vestibular causes of dizziness and unsteadiness in multi-sensory neurological disease can be challenging, with problems typically attributed to central or peripheral nerve involvement. Acknowledging vestibular dysfunction as part of the presentation provides an opportunity to access targeted vestibular rehabilitation, for which extensive evidence exists. A diagnostic framework was developed and validated to detect vestibular dysfunction, benign paroxysmal positional vertigo or vestibular migraine. The specificity and sensitivity of the diagnostic framework was tested in patients with primary mitochondrial disease. METHODS: Adults with a confirmed diagnosis of primary mitochondrial disease were consented, between September 2020 and February 2022. Participants with and without dizziness or unsteadiness underwent remote physiotherapy assessment and had in-person detailed neuro-otological assessment. The six framework question responses were compared against objective neuro-otological assessment or medical notes. The output was binary, with sensitivity and specificity calculated. RESULTS: Seventy-four adults completed the study: age range 20-81 years (mean 48 years, ±SD 15.05 years); ratio 2:1 female to male. The framework identified a vestibular diagnosis in 35 participants, with seven having two diagnoses. The framework was able to identify vestibular diagnoses in adults with primary mitochondrial disease, with a moderate (40-59) to very high (90-100) sensitivity and positive predictive value, and moderate to high (60-74) to very high (90-100) specificity and negative predictive value. CONCLUSIONS: Overall, the clinical framework identified common vestibular diagnoses with a moderate to very high specificity and sensitivity. This presents an opportunity for patients to access effective treatment in a timely manner, to reduce falls and improve quality of life.

Minimally Invasive OSIA Bone Conduction Hearing Implant (MOSIA) in Children: How I do it?

The MOSIA is a novel minimally invasive endoscopic-assisted technique that has been shown to reduce postoperative morbidity and improve aesthetics. This is the first series to include children under the age of 12, as the FDA in the United States only approved OSIA for children 12 and older. Laryngoscope, 134:1901-1906, 2024.

Long-Term Hearing Outcome of Cochlear Implantation in Cases with Simultaneous Intracochlear Schwannoma Resection.

OBJECTIVES: The aim was to analyze the long-term hearing results after simultaneous microsurgical extirpation via enlarged cochleostomy and cochlear implantation in intracochlear schwannoma as compared with non-tumor single-side deafness patients. METHODS: Microsurgical extirpation via enlarged cochleostomy with simultaneous cochlear implantation was performed in 15 cases of intracochlear schwannoma between 2014 and 2021. Speech recognition tests in German language and impedance performances were collected over 36 months of observation and compared with an internal cohort of 52 age matched non-tumor single-side deafness patients. Retrospective cohort study in a tertiary referral center. RESULTS: The surgery proved feasible and uneventful in all cases. In the case of intracochlear schwannoma, the hearing rehabilitation results were highly satisfactory and comparable to those of the non-tumor single-side deafness cohort. The speech recognition performance improved steadily in the first 12 months; afterward, it remained stable, providing indirect evidence against tumor recurrence during the follow-up. One patient required implant revision surgery related to device failure, but no recurrence was registered in the 36 months of observation. CONCLUSIONS: Cochlear implantation is the strategy of choice for hearing rehabilitation in case of intracochlear schwannomas in the long term. In particular, the combination of tumor extirpation via cochleostomy with a cochlear implantation in the same surgical time offers a viable therapy for intracochlear schwannoma, granting a sufficient degree of radicality without compromising the cochlear integrity. This technique allows for revision surgery if required. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1854-1860, 2024.

Reviewing Kampo medicine (Traditional Japanese Herbal Medicine) for otology/neurotology diseases.

Kampo medicine, a traditional Japanese herbal medicine, is used for the treatment of otologic and neurotologic diseases in Japan and other Asian countries. However, only Japanese medical doctors can prescribe both Kampo and modern (Western) medicine. Since a medical doctor can perform not only the diagnosis but also Kampo treatment, it is expected that the quality of clinical studies on traditional herbal medicine is higher in Japan than that in other countries. However, there is no Kampo review written in English language for the treatment of otology/neurotology diseases. Herein, we would like to demonstrate evidence of Kampo treatment for otology/neurotology diseases according to previous studies in Japan.

Vertigo and its burden of disease-Results from a population-based cohort study.

Objectives: Vertigo describes symptoms of abnormal movement of the environment or the patient's own body. As such, it affects patients' quality of life, prevents them from following their daily activities, and increases healthcare utilization. The Global Burden of Disease Project aims to quantify morbidity and mortality worldwide. In 2013, a separate disability weight for vertigo was introduced. The aim of this study is to estimate the symptom burden of disease caused by vertigo. Methods: This study analyzes data from the Gutenberg Health Study (GHS). The GHS is a population-based cohort study representative of the city of Mainz and its district. Participants were asked whether they suffered from vertigo and, if so, how bothered they felt by it, rating their distress on a six-level scale from 1 = little stressful to 6 = extremely stressful. Results: Eight thousand five hundred and nineteen participants could be included in the study. The overall prevalence of vertigo was 21.6% (95%-confidence interval [CI] [20.7%; 22.5%]). Vertigo prevalence peaked in the age group of 55-64 years. Vertigo annoyance averaged 2.42 (±1.28). When an annoyance of 3-6 was considered bothersome, the prevalence of bothersome vertigo was 8.1 % (95%-CI [7.5%; 8.7%]). Age-standardized to the European Standard Population 2013, vertigo caused a burden of 2102 years lived with disability per 100,000 population. Conclusion: In this study, it was found that one in five people suffer at least occasionally from vertigo. This result suggests a significant burden of disease. This burden is reported at the symptom level. Future studies are needed to attribute the burden to specific causes. Level of Evidence: 2.

Contemporary Perspectives in Pathophysiology of Facial Nerve Damage in Oto-Neurological and Skull Base Surgical Procedures: A Narrative Review.

During the last decades, neuro-otological surgery has progressively reduced functional morbidity, including facial nerve damage. However, the occurrence of this sequela may significantly impact on patients' quality of life. The aim of this narrative review is to provide an update on the patho-physiological and clinical issues related to facial nerve damage in oto-neurological and skull base surgery, in the light of a comprehensive therapeutic and rehabilitative approach to iatrogenic disfunctions. The narrative review is based on a search in the PubMed, Scopus, and Web of Science databases. In this surgical setting, the onset of intraoperative facial nerve damage is related to various aspects, mainly concerning the anatomical relationship between tumor and nerve, the trajectory of the surgical corridor, and the boundaries of the resection margins. Mechanisms related to stretching, compression, devascularization, and heating may play a role in determining intraoperative facial nerve damage and provide the patho-physiological basis for possible nerve regeneration disorders. Most of the studies included in this review, dealing with the pathophysiology of surgical facial nerve injury, were preclinical. Future research should focus on the association between intraoperative trauma mechanisms and their clinical correlates in surgical practice. Further investigations should also be conducted to collect and record intraoperative data on nerve damage mechanisms, as well as the reports from neuro-monitoring systems.

COX inhibitor use during definitive radiotherapy is associated with worse hearing preservation in patients with vestibular schwannoma.

PURPOSE: Patients with vestibular schwannoma undergoing definitive radiotherapy commonly experience hearing loss due to tumor and treatment effects; however, there is limited data evaluating concurrent medication use and other clinicopathologic factors associated with hearing preservation during and after radiotherapy. We performed a retrospective cohort study reviewing consecutive patients from 2004 to 2019 treated with radiotherapy for vestibular schwannoma at our institution. METHODS: Ninety four patients with concurrent medications, baseline audiograms, and post-radiotherapy audiograms available were evaluable. We performed chi-squared analyses of the frequency of various clinicopathologic factors and t-tests evaluating the degree of hearing loss based on audiograms. RESULTS: At a median follow-up of 35.7 months (mean: 46.5 months), the baseline pure-tone average (PTA) of the ipsilateral ear worsened from 38.4 to 59.5 dB following completion of radiotherapy (difference: 21.1, 95% CI 17.8-24.4 dB, p < 0.001). 36 patients (38.3%) reported regular use of cyclooxygenase (COX) inhibitors (including acetaminophen and NSAIDs) during radiotherapy. The mean increase in PTA was significantly higher for patients taking COX inhibitors (25.8 dB vs 18.1 dB, p = 0.024) in the ipsilateral ear but not for the contralateral side. COX inhibitor use remained independently associated with worse PTA in the multivariate analysis. CONCLUSION: COX inhibitor use during definitive radiotherapy is associated with worse hearing loss in the affected ear but not for the contralateral side. This suggests the ototoxic effects of COX inhibitors may influence the effects of radiotherapy. These results could have clinical implications and warrant further investigation.

Cellular and Molecular Mechanisms of Vestibular Ageing.

While age-related auditory deficits and cochlear alterations are well described, those affecting the vestibular sensory organs and more broadly the central vestibular pathways are much less documented. Although there is inter-individual heterogeneity in the phenomenon of vestibular ageing, common tissue alterations, such as losses of sensory hair cells or primary and secondary neurons during the ageing process, can be noted. In this review, we document the cellular and molecular processes that occur during ageing in the peripheral and central vestibular system and relate them to the impact of age-related vestibular deficits based on current knowledge.

Evaluation of hearing levels and vestibular function and the impact on cognitive performance in (pre)-symptomatic patients with DFNA9: protocol for a prospective longitudinal study (Rosetta study).

INTRODUCTION: Untreated hearing loss is the largest potentially modifiable risk factor for dementia. Additionally, vestibular dysfunction has been put forward as a potential risk factor for accelerated cognitive decline. Patients with Deafness Autosomal Dominant 9 (DFNA9) present with progressive sensorineural hearing loss and bilateral vestibulopathy and show significantly worse results in cognitive performance compared with a cognitively healthy control group. This highlights the need for adequate treatment to prevent further cognitive decline. This study aims to determine how hearing and vestibular function evolve in (pre-)symptomatic carriers of the p.Pro51Ser mutation in the COCH gene and how this impacts their cognitive performance and health-related quality of life. METHODS AND ANALYSIS: A prospective, longitudinal evaluation of hearing, vestibular function and cognitive performance will be acquired at baseline, 1-year and 2-year follow-up. A total of 40 patients with DFNA9 will be included in the study. The study will be a single-centre study performed at the ORL department at the Antwerp University Hospital (UZA), Belgium. The control group will encompass cognitively healthy subjects, already recruited through the GECkO study. The primary outcome measure will be the Repeatable Battery for the Assessment of Neuropsychological Status adjusted for the Hearing-Impaired total score. Secondary outcome measures include Cortical Auditory-Evoked Potentials, vestibular assessments and health-related quality of life questionnaires. The expected outcomes will aid in the development of gene therapy by providing insight in the optimal time window for the application of gene therapy for the inner ear. ETHICS AND DISSEMINATION: The ethical committee of UZA approved the study protocol on 19 December 2022 (protocol number B3002022000170). All participants have to give written initial informed consent in accordance with the Declaration of Helsinki. Results will be disseminated to the public through conference presentations, lectures and peer-reviewed scientific publications.