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Clinical Analysis Of Disorders Of Hearing And Balance

听力和平衡障碍的临床分析

基本信息

批准号：
9352075
负责人：
Carmen Crowell Brewer
金额：
$ 89.17万
依托单位：
NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9352075
关键词：
Acoustic Nerve Action Potentials Adolescent Affect Age Alleles Alstrom syndrome American Aminoglycosides Antineoplastic Agents Area Audiology Audiometry Auditory Auditory system Brain Neoplasms Characteristics Child Clinical Clinical Management Clinical Protocols Clinical Research Clinical Trials Collaborations Collection Complex Congenital Disorders Data Data Analyses Data Collection Data Set Development Diagnostic Discrimination Disease Ear Diseases Early Diagnosis Equilibrium Equipment Evaluation Explosion Exposure to Familial amyloid nephropathy with urticaria and deafness Family Fanconi&apos s Anemia Frequencies Functional disorder Gangliosidoses Gender Genes Genetic Genotype Goals Head and neck structure Hearing Heritability Hospitals Image Individual Inherited Institutes Interleukin-1 beta International Intervention Laboratories Magnetic Resonance Imaging Manuscripts Masks McCune-Albright Syndrome Measures Methodology Modality Monitor Musculoskeletal Equilibrium Mutate Mutation National Human Genome Research Institute National Institute of Allergy and Infectious Disease National Institute of Arthritis and Musculoskeletal and Skin Diseases National Institute of Child Health and Human Development National Institute of Dental and Craniofacial Research National Institute of Neurological Disorders and Stroke National Institute on Deafness and Other Communication Disorders Natural History Neonatal Neurofibromatosis 1 Neurofibromatosis 2 Neuropathy Noise Oculocutaneous Albinism Osteogenesis Imperfecta Otolaryngology Otology Parents Patients Perception Persons Phase Phenotype Physiological Preparation Principal Investigator Process Protocols documentation Publications Publishing Radiation therapy Reference Values Reporting Research Research Design Research Personnel Research Support Risk Role Safety Sex Chromosomes Siblings Signal Transduction Smith Magenis syndrome Societies Speech Stimulus Subgroup Supraoptic Vertical Ophthalmoplegia Syndrome System Testing Time Transcranial magnetic stimulation Twin Multiple Birth United States National Institutes of Health Usher Syndrome Variant Vestibular Aqueduct Vision Von Hippel-Lindau Syndrome Work Xeroderma Pigmentosum Zein anakinra autoinflammatory base bone marrow failure syndrome comparative deafness glycosylation healthy volunteer hearing impairment hydroxypropyl-beta-cyclodextrin improved interest meetings middle ear otoacoustic emission otoconia ototoxicity ototoxin posters proband programs research clinical testing research study skills sound symposium tumor tumor growth

项目摘要

1. We continue to acquire normative data for various aspects of auditory and vestibular function. This data is used to develop normal reference ranges for test interpretation and as control data for comparison to results obtained in various patient groups in our collaborative research endeavors. We are also examining the effects of various methodologies, stimulus characteristics, test equipment, and subject characteristics (e.g., age, gender) on normal function, and are evaluating variability of auditory and vestibular measures over time. To date we have focused on the development of normative and comparative data for tests of otolith function. 2. We extended our work examining heritability of auditory processing abilities using a twins paradigm with Drs. Griffith & Friedman (NIDCD), Dr. Moore (Cincinnati Childrens Hospital), and Dr. Zobay (Institute for Hearing Research, UK). Initially, we showed heritability of several speech based auditory processing skills. Recently, we published findings demonstrating heritability for skills related to frequency discrimination and perception of signals in the presence of masking sounds (Brewer et al., 2016). This work has implications for those interested in the genetic underpinnings of auditory processing. 3. We initiated development of a test protocol to determine the stability of the auditory nerve action potential and otoacoustic emissions over time in a group of healthy volunteers. The goals are to determine feasibility of these physiologic measures as markers of damage to the auditory system from noise or ototoxic agents and to determine hearing safety following prolonged exposure to MRI noise while using hearing protection in support of research being conducted by Drs. Duyn & Picchioni (NINDS). 4. In collaboration with Dr. Griffith (NIDCD), we continued auditory and vestibular phenotypic assessments of individuals with enlarged vestibular aqueducts (EVA) as well as their siblings and parents. To date, over 100 probands and their families have been ascertained. We published one manuscript on vestibular characteristics (Zalewski et al., 2015) and have submitted another that examines longitudinal progression of hearing in persons with EVA and 1 or 2 mutated alleles in the SLC26A4 gene. 5. In collaboration with Dr. Griffith (NIDCD), we evaluated auditory function in 2 families with NLRP3 mutations and examined the effects of interleukin-1 beta blockade therapy on hearing acuity. This work has been submitted for publication. 6. In collaboration with Drs. Friedman & Griffith (NIDCD) and Dr. Zein (NEI), we continue to study hearing and balance function in persons with Usher syndrome. We are interested in postural balance skills and their relationship to vestibular and visual function, type of Usher syndrome, genotype, and the progression/decline of these skills over time. We have one manuscript in preparation that details comprehensive balance function in the three types of Usher syndrome. 7. In collaboration with Dr. Friedman (NIDCD), we reviewed and interpreted audiograms collected from outside facilities, and assisted in preparation of a manuscript reporting variability in presentation of recessively inherited hearing loss suggesting a prominent role of genetic and environmental modifiers (Naz et al., 2016). 8. In collaboration with Dr. Porter (NICHD), we are participating in phase 1 and phase 2/3a trials of hydroxypropyl beta cyclodextrin for treatment of Niemann Pick type C disease. Our roles include auditory monitoring, ototoxicity grading, and reporting to FDA and safety monitors. We are preparing a manuscript with Dr. Porter. 9. In collaboration with Dr. Gahl (NHGRI), we identified progressive auditory dysfunction, similar to auditory neuropathy, as a characteristic of the newly described NGLY1 deficiency. This work was presented at the American Auditory Society meeting in 2016 (Brewer et al.) and was included in a recently published manuscript (Lam et al., 2016). 10. In collaboration with Dr. Alter (NCI), we published a manuscript detailing the auditory characteristics of persons with Fanconi Anemia and other inherited bone marrow failure syndromes (Kalejaiye et al., 2016). 11. In collaboration with A. Smith (NHGRI), we characterized hearing in persons with Smith Magenis Syndrome and currently have a manuscript under review. 12. In collaboration with Dr. Biesecker, we evaluated patients with and without mutations in the MYO1A gene in an effort to determine and challenge the association of this gene with non-syndromic deafness. Our manuscript is currently in review. 13. In collaboration with Drs. Hallett (NINDS) & Damiano (CC) we investigated hearing before and after exposure to transcranial magnetic stimulation in a group of adolescents; our manuscript is currently in review. 14. In collaboration with Dr. Gunay-Aygun (NHGRI) we are preparing a manuscript describing the auditory phenotype and progression of hearing loss in persons with Alstrom syndrome. Preliminary data were presented at the Alstrom Syndrome International Conference in 2016 (Gunay-Aygun). 15. In collaboration with Dr. Chittiboina (NINDS), we are investigating auditory and vestibular function in persons with neurofibromatosis type 2. We are interested in the relationship of these measures to tumor size and sensitivity of these assessments in early detection of tumor growth with the goal of improving clinical management. We are analyzing progression of auditory and vestibular findings in a subgroup with small tumors to better understand the relative timing of clinical versus anatomical changes. 17. In collaboration with Dr. Goldbach-Mansky (NIAMS) we continued auditory evaluation of patients with autoinflammatory disorders, including Muckle Wells syndrome and neonatal onset autoinflammatory disorder. We are preparing a manuscript examining the course of hearing over a 5-year monitoring period for those who have been treated with anakinra. The initial description of this data was presented at COSM in 2016 (Gao et al.). 18. In collaboration with Dr. M. Collins (NIDCR) we have initiated an in-depth analysis of hearing and middle ear function as well as otology and imaging findings in persons with McCune Albright Syndrome. The initial analysis of this data will be presented at the ASBMR in Sept. 2016 (Boyce et al.). 19. In collaboration with other NIH investigators, we are evaluating auditory function in persons with oculocutaneous albinism (Adams, NHGRI), neurofibromatosis type 1 (Widemann, NCI), congenital disorders of glycosylation (Wolfe & Gahl, NHGRI), Moebius syndrome (Mannoli, NHGRI), and gangliosidosis types 1 and 2 (Tifft, NHGRI). We are interested in the auditory phenotype, including auditory processing of dichotic and other complex sounds, and relationships to other aspects of the disease/disorder and genotype. 20. We continue to evaluate natural history of auditory function in persons with von Hippel-Lindau disease (Heiss, NINDS), WHIMS (McDermott, NIAID), osteogenesis imperfecta (Marini, NICHD), sex-chromosome variants (Muenke, NHGRI), xeroderma pigmentosum (Kraemer & Digiovanna), Smith-Lemli-Optiz syndrome (Porter, NICHD) and the Undiagnosed Diseases Program (Gahl, NHGRI). We are interested in auditory phenotype, natural history of hearing, and relationships to other aspects of disease/disorder and genotype. 21. In collaboration with Wasserman & LoPresti (NINDS), we are examining the effects of repeated breacher explosions on the auditory/vestibular systems. 22. In collaboration with other NIH investigators, we continue our comprehensive monitoring program for persons participating in clinical trials in which there may be risk of ototoxicity. These include aminoglycosides, antineoplastic compounds and radiation therapy for brain tumors.

1. 我们继续获得听觉和前庭功能各方面的规范数据。该数据用于制定测试解释的正常参考范围，并作为对照数据，用于与我们合作研究中不同患者组获得的结果进行比较。我们还研究了各种方法、刺激特征、测试设备和受试者特征（如年龄、性别）对正常功能的影响，并评估了听觉和前庭测量随时间的变化。迄今为止，我们一直专注于耳石功能测试的规范和比较数据的发展。