Clinical Analysis of Disorders of Hearing and Balance

National Institute On Deafness And Other Communication Disorders

Investigators

Linked publications, trials & patents

Abstract

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 focus has targeted algorithms used to interpret postural stability in health volunteers and patients at risk for falls. We have presented this work internally and at multiple scientific meetings in the past year (Wafa et al., ASHA, Am Balance Society, Am Auditory Society, and Am Acad of Audiology). We are designing a sub-study to define normal ranges and stability of otoacoustic emission measures and electrocochleography in support of work conducted 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 clinical trial that is set to begin soon. *Dr. Hoa in preparation, design and implementation of his translational research protocol examining characteristics of fluctuating hearing loss. *Dr. Chien, in development and implementation of his longitudinal protocol examining the time course of hearing loss in patients/families with autosomal dominant nonsyndromic hearing loss. Trans-NIH Collaborations *With investigators in NHLBI, NIAID and NCI, we continue comprehensive monitoring programs 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 presented a poster (Lacey et al, Am Acad Audiology, 2021) and are preparing a manuscript on prevalence and risk factors for amikacin ototoxicity (Chisholm et al.) in collaboration with NHLBI investigators (Olivier & Fennelly). With Drs. Williamson & Anjum (NIAID), we published a manuscript examining clinical benefits, including those involving the auditory system, of pulse-taper steroids in patients with non-HIV cryptococcal meningitis (Anjum et al., 2021) With Dr. Porter (NICHD), we continued participation in a natural history study of Niemann Pick type C disease and a phase 2/3 treatment trial of hydroxypropyl beta cyclodextrin for this disease. Additionally, we have worked with Dr. Porter to examine auditory function in patients with Smith-Lemli-Opitz syndrome(Zalewski et al., 2021). With Dr. Widemann (NCI), we conducted a detailed examination of auditory function in persons with neurofibromatosis type I (NF1). A manuscript is nearing completion (Idowu & Christensen, et al). We also examined auditory outcomes in NF1 patients treated with selumetinib (Christensen et al., poster, Children's Tumor Foundation, 2021). 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. This work was recently published (Wafa et al. 2021) along with another that reviews the classification of atypical Usher syndrome (Zein et al., 2020). With Dr. Guerrerio (NIAID), we are studying auditory function in patients with Loeys Dietz syndrome. During the past year we had 2 conference presentations (Jeon et al., OTO-HNS and Christensen, Am Acad Audiology), along with publication of a manuscript detailing the auditory and otologic phenotype (Jeon & Christensen et al., 2021). With Dr. Goldbach-Mansky (NIAMS), we continue auditory evaluation of patients with autoinflammatory disorders, including neonatal onset autoinflammatory 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 are examining auditory & vestibular function in persons with Chiari malformation and presented a summary at the Am Balance Society in 2021 (Famili, Zalewski, et al.). With Dr. Venditti (NHGRI), we examined the auditory phenotype of persons with methylmalonic acidemia and are developing a manuscript (Zalewski et al.). With Dr. Dang Do (NICHD), we participated a longitudinal study of patients with Batten disease/CLN3. We presented a poster on describing changes to the auditory brainstem response during sedation (Chisholm et al., 2021 Am Acad Audiology). A multidisciplinary manuscript is in preparation (Dang Do et al.). With Dr Huryn (NEI), we contributed to a manuscript reporting the clinical features of Heimler syndrome (Daich Varela et al., 2020)and continue to gather auditory and vestibular data on patients with spinocerebellar ataxia type-7. With Dr. Ferreira (NHGRI) we examined the auditory phenotype of patient with generalized arterial calcification of infancy and are currently preparing a manuscript (Theng et al.). With Drs. Ferrada and Grayson (NIAMS), we collected data to describe the auditory phenotype of relapsing polychrondritis. We have initiated analysis of this data and plan to develop a manuscript over the upcoming year. With Drs. Kramer (NCI)& Lehky (NINDS) we examined the relationship between sensorimotor neuropathies and auditory function in persons with xeroderma pigmentosum (Lehky et al., manuscript under review, poster at Soc of Investigative Dermatology). Other Intramural Collaborations Associate investigator status on the following new protocols: *Dr. Stewart (NHGRI), Clinical, Genetic and Epidemiologic Study of Children and Adults with RASopathies. *Dr. Lisanby (NIMHS), Role of GABAergic transmission in auditory processing in Autism Spectrum Contributed to deep phenotyping protocols in natural history studies of hearing loss & vestibular function, and relationships to other aspects of diseases/disorders and genotype include: NF2 (Chittiboina, NINDS), congenital disorders of glycosylation (Wolfe, NHGRI), gangliosidosis types 1&2 (Tifft, NHGRI), GATA2 (Holland, NIAID), McCune Albright Syndrome (Boyce, NIDCR), osteogenesis imperfecta (Marini, NICHD), propionic acidemia (Venditti, NHGRI), and von Hippel-Lindau disease (Heiss, NINDS) Participated as members of a team examining multiple systems in persons who have experienced trauma of unknown origin (Chan, CC). Our contributions include deep auditory & vestibular phenotyping. Summaries of these findings have been presented to several government agencies. We contributed to clinical characterization of auditory & vestibular function of patients in the Undiagnosed Diseases Program (Gahl, NHGRI) and provided supportive clinical evaluations to other protocols at NIH. Extramural Collaborations With Drs. Carr, Modica (Walter Reed) & Wasserman (NINDS), we examined and published findings on the effect of repeated breacher explosions on the auditory and vestibular systems (Modica et al. 2021). With Drs. Iannaccone (Duke), Duncan (UCSF) & Hufnagel (NEI), Dr. Brewer examined the audiometric phenotype of large group of patients with Usher syndrome type 2 caused by mutations in the USH2A gene (Iannaccone, Brewer et al., 2021) With Dr. Hallett (NINDS) and a group of international experts, Dr. Brewer participated in development of international safety guidelines for TMS (Rossi et al., 2021). With Drs. Garinis (OHSU), Poling (Mayo), Steyger (Creighton), Konrad -Martin (VA) & others, Dr. Brewer contributed to a manuscript providing guidelines for ototox