Clinical Analysis of Disorders of Hearing and Balance

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The Audiology Unit continued our protocol, Normative Values in Audiovestibular Testing. This protocol is used to establish normal reference ranges and control data for comparison to results obtained for various patient groups in our collaborative research endeavors. We are also examining the effects of various methodologies, stimulus characteristics, and subject characteristics (e.g., age, sex) on normal function, and are evaluating variability of auditory and vestibular measures over time. Our recent work targeting algorithms used to interpret postural stability was recently accepted in Posture in Gait (Wafa et al., 2023). We are currently implementing a sub-study to define normal ranges and stability of otoacoustic emission measures and electrocochleography in support of work conducted with Dr. Hoa (NIDCD, see below). NIDCD collaborations include work with the following PIs: Dr. Cunningham in her work examining the effect of statins in prevention of cisplatin ototoxicity. This includes a retrospective study (Fernandez et al., 2021) and a prospective U01 clinical trial that is set to begin soon. Dr. Hoa in development, design and implementation of his translational research protocol examining characteristics of fluctuating hearing loss. Dr. Chien, in development, design and implementation of his longitudinal protocol examining the time course of hearing loss in patients/families with autosomal dominant non-syndromic hearing loss and in support of his development of a new protocol looking at functional balance problems experienced by persons with Usher syndrome. Trans-NIH Collaborations (non-exhaustive list) With Dr. Ferreira (NHGRI) we examined the auditory phenotype of patient with generalized arterial calcification of infancy (GACI) and have published manuscript detailing this work (Theng, et al. 2022). With Drs. Williamson & Anjum (NIAID), we continue to evaluate patients with non-HIV cryptococcal meningitis and abnormalities involving the auditory system associated with pulse-taper steroids (Anjum et al., 2021) With Dr. Porter (NICHD), we continued participation in a natural history study of Niemann Pick type C disease. Additionally, we continue previous work with Dr. Porter and colleagues to examine auditory function in patients with Smith-Lemli-Opitz syndrome (Zalewski et al., 2021). With Dr. Widemann (NCI), we continue to investigate auditory function in persons with neurofibromatosis type I (NF1) receiving a MEK inhibitor therapy and have recently published a phenotype manuscript describing auditory function in patient with NF1 (Idowu & Christensen, et al., 2022). With Drs. Friedman (NIDCD) & Zein (NEI), we studied hearing and balance function in persons with Usher syndrome. We were interested in postural balance skills and their relationship to vestibular and visual function, type of Usher syndrome, and genotype and published a manuscript on this work (Wafa et al. 2021) in addition to contributing to a paper on proposed therapy for Usher syndrome associated with protocadherin deficiency (Sethna et al. 2021). Work with Usher syndrome is ongoing. With investigators from NHLBI, NIAID and NCI, we continue to manage a comprehensive surveillance program for persons participating in treatments and clinical trials in which there may be risk of ototoxicity. These include aminoglycoside antibiotics, platinum-based anti-neoplastic compounds, new agents and radiation therapy for brain tumors. We are preparing a manuscript on prevalence and risk factors for amikacin ototoxicity (Chisholm et al.) in collaboration with NHLBI investigators (Olivier & Fennelly). With Dr. Goldbach-Mansky (NIAMS), we continue auditory evaluation of patients with auto-inflammatory disorders, including neonatal onset auto-inflammatory disorder (NOMID). We have examined data at a 10-year time point post initiation of anakinra in patients with NOMID. A manuscript describing the longitudinal trajectory of hearing loss (Alehashemi et al.) is in preparation. With Drs. Heiss & Cantor (NINDS), we published a paper examining auditory & vestibular function in persons with Chiari malformation (Famili, Zalewski, et al, 2023). With Dr. Venditti (NHGRI), we examined the auditory phenotype of persons with methylmalonic acidemia and are preparing a manuscript (Zalewski et al.). With Drs Chittiboina (NINDS), Kim (NIDCD), and Laws (NINDS), we have begun a comprehensive vestibular data analysis project involving 10+ years of longitudinal vestibular (and hearing) data and neuroimaging data. New Intramural Collaborations / Associate investigator status on the following protocols: Drs. Stewart and Shepard (NHGRI), Clinical, Genetic and Epidemiologic Study of Children and Adults with RASopathies. Dr. Oberman (NIMHS), Role of GABAergic transmission in auditory processing in Autism Spectrum Dr. Sidransky (NHGRI), Gaucher Disease Contributed deep phenotyping protocols in natural history studies of hearing loss & vestibular function, and relationships to other aspects of diseases/disorders and genotype include: spinocerebellar ataxia type-7 (Huryn, NEI), Batten disease/CLN3 (Dang Do, NICHD), relapsing polychrondritis (Ferrada and Grayson, NIAMS), congenital disorders of glycosylation (Wolfe, NHGRI), gangliosidosis types 1&2 (Tifft, NHGRI), GATA2 (Holland, NIAID), McCune Albright Syndrome (Boyce, NIDCR), and osteogenesis imperfecta (Marini, NICHD), propionic acidemia (Venditti, NHGRI). Continued collaborative multi-disciplinary Clinical Center team examining persons who have experienced trauma of unknown origin associated with Anomalous Health Incidents (AHI)(Chan, CC). Our contributions include deep auditory & vestibular phenotyping. Summaries of these findings are currently being finalized for submitting two concurrent multi-disciplinary manuscripts (submission pending). Continued clinical characterization of auditory & vestibular function of patients in the Undiagnosed Diseases Program (Dr. Gahl, NHGRI) and continued clinical support to other protocols and ICs across the NIH. Noteworthy extramural collaborations: External collaborations through the HEARShare consortium are currently investigating how to better leverage data visualization and analysis tools (e.g., PODVis) to handle large-scale data sets. This project involves pursuance of grant funding to facilitate data sharing opportunities and strengthen the collaborative network of scalable hearing (and potential vestibular) data. Additional data collaborations with extramural software developers, we have developed and expanded the current utility of our audiometric data tracking software to integrate patient diagnosis into our data tracking system using a custom program utilizing ICD-10 coding system and unique clinical modifiers. Additionally, we have also integrated audiometric hearing results directly into the CRIS electronic medical record, incorporating an electronic signature and immediate upload into the CRIS EMR and data exportation / access via the BTRIS system by intramural collaborators. With use of NIH STRIDES funding (Science and Technology Research Infrastructure for Discovery, Experimentation, and Sustainability Initiative), we successfully implemented a cloud-based Azure data storage infrastructure to automatically and seamlessly store all hearing data. Together with extramural collaborations, we aim to extend this storage infrastructure to include auditory evoked potential (AEP) and otoacoustic emission (OAE) data and incorporate all hearing-related data to an NIDCD-specific data visualization tool (e.g., PODVis) to increase access for real-time data analytics. Such efforts work towards efforts of potentially increasing access to large data sharing opportunities both within the intramural NIH programs and across intramural and extramural programs.