Clinical Analysis Of Disorders Of Hearing And Balance

听力和平衡障碍的临床分析

• 批准号: 9147432
• 负责人: Carmen Crowell Brewer
• 金额: $ 91.78万
• 依托单位: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
• 依托单位国家: 美国
• 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/9147432
• 关键词: Affect; Age; Alstrom syndrome; Aminoglycosides; Antineoplastic Agents; Area; Audiology; Auditory; Brain Neoplasms; Characteristics; Child; Clinical; Clinical Management; Clinical Protocols; Clinical Research; Collaborations; Collection; Complex; Congenital Disorders; Data; Data Analyses; Data Collection; Data Set; Development; Diagnostic; Disease; Disease Progression; Ear Diseases; Early Diagnosis; Effectiveness; Equilibrium; Equipment; Evaluation; Evoked Potentials; Explosion; Exposure to; Familial amyloid nephropathy with urticaria and deafness; Familial disease; Family; Fanconi' s Anemia; Gangliosidoses; Gender; Genotype; Goals; Head and neck structure; Hearing; Heritability; Hospitals; Individual; Inflammatory; Inherited; Institutes; International; Intervention; Laboratories; Magnetic Resonance Imaging; Manuscripts; McCune-Albright Syndrome; Measures; Methodology; Modality; Monitor; Musculoskeletal Equilibrium; Mutation; Mycobacterium Infections; National Heart, Lung, and Blood Institute; 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; Neurilemmoma; Neurofibromatosis 1; Neurofibromatosis 2; Nuclear Pore Complex; Oculocutaneous Albinism; Osteogenesis Imperfecta; Otolaryngology; Parents; Patients; Performance; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phase I Clinical Trials; Phenotype; Polyostotic fibrous dysplasia; Preparation; Principal Investigator; Procedures; Process; Protocols documentation; Publications; Publishing; Radiation therapy; Reference Values; Reporting; Research; Research Design; Research Personnel; Risk; Role; Safety; Siblings; Smith Magenis syndrome; Societies; Speech; Stimulus; Stuttering; Syndrome; System; Test Result; Testing; Time; Transcranial magnetic stimulation; Trichothiodystrophy; Twin Multiple Birth; United States National Institutes of Health; Usher Syndrome; Variant; Vestibular Aqueduct; Vision; Von Hippel-Lindau Syndrome; Work; Xeroderma Pigmentosum; Y Chromosome; Zein; anakinra; base; bone marrow failure syndrome; comparative; glycosylation; hearing impairment; hydroxypropyl-beta-cyclodextrin; improved; interest; meetings; otoacoustic emission; otoconia; ototoxicity; ototoxin; outcome forecast; posters; proband; programs; research clinical testing; research study; skills; sound; trait

1. The Audiology Unit continues to acquire normative data for various aspects of auditory and vestibular function. This data serves as reference ranges of normal performance by which test results can be interpreted, and will be used as control data for comparison to data obtained in various patient groups in our collaborative research endeavors. We are also examining the effects of various methodologies, stimulus characteristics, test equipment, test paradigms, and the influence of non-pathologic subject characteristics (e.g. age, gender) on normal function, and 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 and have made 2 presentations at professional society meetings on this topic (Zalewski et al. 2014) and have a manuscript in preparation. 2. In collaboration with Drs. Griffith and Friedman (NIDCD), Dr. Moore (Cincinnati Childrens Hospital), and Dr. Zobay (Institute for Hearing Research, UK), we examined heritability of temporal and spectral auditory processing skills using non-speech tests. These tests were administered to twin pairs in an effort to determine if auditory processing skills are inherited traits. We have previously identified heritability of speech-based auditory processing skills and this current work extends our research to demonstrate heritability for non-speech stimuli. We have a manuscript in submission. 3. In collaboration with the Dr. Griffith (NIDCD), the Audiology Unit performs auditory and vestibular phenotypic assessments of individuals with enlarged vestibular aqueducts as well as their siblings and parents. Over 90 probands and their families have been ascertained. We continue to search for phenotypic features that predict genotype and clinical prognosis. We have published one manuscript on vestibular characteristics (Zalewski et al., 2015) and have another in preparation. 4. In collaboration with Drs. Friedman and Griffith (NIDCD) and Dr. Zein (NEI), the Audiology Unit continues to study auditory 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. Over this reporting period we have one publication (Zein et al., 2014) and have one manuscript in preparation. 5. In collaboration with Dr. Drayna (NIDCD), we evaluated auditory function in a large family with AP4E1 mutations and stuttering. This work is included in a submitted manuscript describing the phenotype of these individuals. 6. In collaboration with Dr. Cunningham (NIDCD), we initiated development of a test protocol to document the effectiveness of an otoprotective methodology for patients receiving ototoxic medications. 7. In collaboration with Drs. Heiss and Chittiboina (NINDS), we are investigating hearing, electrophysiologic auditory function, vestibular function, and postural balance in persons with neurofibromatosis type 2 (NF2). We are interested in the relationship of these measures to cochleovestibular schwannoma size, the natural history of disease progression, and sensitivity of these assessments in early detection with the goal of improving clinical management of those with NF2. 8. In collaboration with Dr. Porter (NICHD), we participated in a phase 1 trial of hydroxypropyl beta cyclodextrin (HPBCD) for treatment of Neimann Pick Type C disease. Our roles include monitoring of auditory function and grading of ototoxicity, participation on the safety committee, participation in the NIH/NCATS NPC Ototoxicity Meeting, and in other discussions regarding this treatment. We presented our preliminary research on ototoxicity related to HPBCD at the Association for Research in Otolaryngology meeting in 2015. 9. In collaboration with Dr. Goldbach-Mansky (NIAMS) we continued evaluation of auditory manifestations of neonatal onset multi-system inflammatory disorder (NOMID), familial cold auto-inflammatory syndrome, and Muckle-Wells syndrome and the effectiveness of several drug therapies. We are currently analyzing data and preparing a manuscript examining the course of hearing over a 5-year monitoring period for those who have been treated with anakinra. 10. In collaboration with Dr. Holland, (NIAID) we collected research data and contributed to a manuscript examining the phenotypic effects of GATA3 insufficiency (Lawrence et al., 2015). 11. In collaboration with Dr. Gunay-Aygun (NHGRI) we presented a poster at a professional society meeting that highlighted our research on auditory function, including evoked potentials, in persons with Alstrom syndrome (Lindsey et al., 2015) and are currently developing a manuscript. 12. In collaboration with Dr. Venditti (NHGRI) we evaluated and analyzed the natural history of auditory function in patients with methylmelonic acidemia. This resulted in a poster presentation (Manoli et al., 2015) at a professional society meeting. A manuscript is in preparation. 13. In collaboration with other NIH investigators, we are evaluating hearing, electrophysiologic auditory function, and auditory processing manifestations in persons with oculocutaneous albinism (Adams, NHGRI), neurofibromatosis type 1 (Widemann, NCI), congenital disorders of glycosylation (CDG)(Wolfe & Gahl, NHGRI), Moebius syndrome (Mannoli, NHGRI), and gangliosidosis types 1 and 2 (Tifft, NHGRI). We are interested in the auditory phenotype, including processing of dichotic and other complex sounds, and relationships to other aspects of the disease/disorder and genotype. We contributed to professional society poster on the topic of hearing loss in persons with CDG (Ferreira et al. 2015). 14. We continue to evaluate natural history of auditory function in persons with Fanconi anemia and other inherited bone marrow failure syndromes (IBMFS) (Alter, NCI), McCune-Albright syndrome and polyostotic fibrous dysplasia (M. Collins, NIDCR), von Hippel-Lindau disease (Lonser, NINDS), Smith-Magenis syndrome (Smith, NHGRI), WHIMS (McDermott, NIAID), osteogenesis imperfecta (Marini, NICHD), Y-Chromosome variants (Muenke, NHGRI), xeroderma pigmentosum and trichothiodystrophy (Kraemer & Digiovanna) and the Undiagnosed Diseases Program (Gahl, NHGRI). We are interested in the auditory phenotype, natural history of hearing, and relationships to other aspects of disease/disorder and genotype. 15. In collaboration with investigators from NINDS (Wasserman & LoPresti), we are evaluating hearing and vestibular function in persons with exposure to breacher explosions. We are examining the effects of repeated exposures on the auditory and vestibular systems. 16. In collaboration with other investigators the NIH, we continue to implement and analyze studies of the auditory and/or vestibular system of persons participating in clinical procedures or therapies in which there may be risk of ototoxicity. These include aminoglycosides for mycobacterium infections (Holland, NIAID & Olivier, NHLBI), antineoplastic compounds (Hassan, NCI), radiation therapy for brain tumors (Warren, NCI), and transcranial magnetic stimulation (Hallett & Damiano, NINDS). We presented a poster on long term monitoring of hearing and otoacoustic emissions in children receiving CNS radiation therapy at a professional meeting (Stakhovskaya et al, 2015).

1。听力学部门继续获取有关听觉和前庭功能各个方面的规范数据。该数据用作正常绩效的参考范围，可以解释测试结果，并将用作控制数据，以与我们协作研究中各个患者组获得的数据进行比较。 我们还正在研究各种方法，刺激特征，测试设备，测试范例以及非病理学学科特征（例如年龄，性别）对正常功能的影响，并评估随着时间的推移听觉和前庭度量的变异性。 迄今为止，我们一直专注于针对耳石功能测试的规范性和比较数据的发展，并在专业社会会议上就此主题进行了2次演讲（Zalewski etal。2014），并准备了一份手稿。 2。与Drs合作。格里菲斯（Griffith）和弗里德曼（NIDCD），摩尔博士（辛辛那提儿童医院）和Zobay博士（英国听力研究所），使用非语音测试检查了时间和频谱听觉处理技能的遗传力。将这些测试用于双对，以确定听觉处理技能是否是继承的特征。我们以前已经确定了基于语音的听觉处理技巧的遗传力，而这项当前的工作扩展了我们的研究，以证明非语音刺激的遗传力。我们有一个手稿。 3。与Griffith博士（NIDCD）合作，听力学部门对前庭渡槽及其兄弟姐妹和父母进行了听觉和前庭表型评估。已经确定了90多个概率及其家人。我们继续寻找预测基因型和临床预后的表型特征。我们已经发表了一份有关前庭特征的手稿（Zalewski等，2015），并进行了另一种准备。 4。与Drs合作。弗里德曼（Friedman）和格里菲斯（Griffith）（NIDCD）和Zein博士（NEI），听力学部门继续研究听觉和平衡功能，患有Usher综合征的人。我们对姿势平衡技能及其与前庭和视觉功能的关系，usher综合征，基因型的类型以及这些技能随着时间的推移的发展/下降感兴趣。在此报告期间，我们有一个出版物（Zein等，2014），并准备了一个手稿。 5。与Drayna博士（NIDCD）合作，我们评估了具有AP4E1突变和口吃的大型家庭中的听觉功能。这项工作包括在描述这些人表型的提交手稿中。 6。与Cunningham博士（NIDCD）合作，我们启动了测试方案的开发，以记录对接受耳毒性药物的患者的耳状保护方法的有效性。 7。与Drs合作。 Heiss和Chittiboina（Ninds），我们正在研究听力，电生理听觉功能，前庭功能和姿势平衡2型神经纤维瘤病（NF2）。我们对这些措施与耳目骨鱼鞘裂片的大小，疾病进展的自然史以及这些评估的敏感性的关系感兴趣，目的是改善NF2患者的临床管理。 8。与Porter博士（NICHD）合作，我们参加了一项1阶段的羟丙基β环糊精（HPBCD）的试验，以治疗Neimann Pick C型疾病。我们的角色包括监测听觉功能和耳毒性的评分，参加安全委员会的参与，参加NIH/NCATS NPC NPC耳毒性会议，以及有关此治疗方法的其他讨论。 我们在2015年耳鼻喉科研究协会上介绍了与HPBCD有关的耳毒性的初步研究。 9。与Goldbach-Mansky博士（NIAMS）合作，我们继续评估新生儿发作多系统炎症障碍（Nomid），家族性冷自身炎症综合征和粘液孔综合征的听觉表现形式以及几种药物疗法的有效性。我们目前正在分析数据并准备一份手稿，以检查接受Anakinra治疗的人在5年的监测期内进行听力。 10。与荷兰博士（NIAID）合作，我们收集了研究数据，并为检查GATA3不足的表型效应做出了贡献（Lawrence等，2015）。 11。与Gunay-Aygun博士（NHGRI）合作，我们在一次专业协会会议上介绍了一张海报，该海报在患有Alstrom综合征的人（Lindsey等人，2015年）中强调了我们关于听觉功能的研究，包括引人注目的潜力，目前正在开发一份手稿。 12。与Venditti博士（NHGRI）合作，我们评估并分析了甲基甲基酸血症患者的听觉功能的自然历史。这导致了在专业社会会议上的海报演讲（Manoli等，2015）。手稿正在准备。 13。与其他NIH研究者合作，我们正在评估听力，电生理学听觉功能以及听觉处理表现，患有眼皮白化病（Adams，NHGRI），神经纤维瘤病，1型（Widemann，NCI）的人（NCI，NCI），gllycosylation（Mo）（CDG）（CDG）（cdg＆gious，nhllll offofeious，nhllll offofe＆ggiiim）， （Mannoli，NHGRI）和神经节病型1和2（TIFFT，NHGRI）。 我们对听觉表型感兴趣，包括处理二分法和其他复杂声音，以及与疾病/障碍和基因型其他方面的关系。我们为与CDG患者的听力损失的主题为专业社会海报做出了贡献（Ferreira等，2015）。 14。我们继续评估富康尼贫血和其他遗传骨髓衰竭综合征（IBMFS）（ALTER，NCI），McCune-Albright综合征和多质纤维化综合性异常成倍体的人（IBMFS）（IBMFS）（IBMFS）（M. Collins，Nidcr），Von-Hippel-lindau病（M. Collins），NINDS，史密斯（M. Collins）（史密斯），史密斯（M. Collins）（M. Collins），史密斯（M. Collins）（M. Collins），史密斯（M. Collins），史密斯（M. collins）， NHGRI），WHIMS（MCDERMOTT，NIAID），成骨不完美（Marini，NICHD），Y-chromosom体变体（Muenke，NHGRI），Xeroderma cipmentosum和Trichothiodyodyodyodyodyodyodyodyodyodyodyodyodyodyodyodyrophy（Kraemer＆Digiovanna）（Kraemer＆digiovanna）以及nhned isses nhhnhebi（Gahned nhnepearse）。我们对听觉表型，自然史以及与疾病/混乱和基因型其他方面的关系感兴趣。 15。与Ninds（Wasserman＆Lopresti）的调查人员合作，我们正在评估暴露于Breacher爆炸的人的听力和前庭功能。我们正在研究重复暴露对听觉和前庭系统的影响。 16。与其他研究人员合作，我们继续对参加可能存在耳毒性风险的临床程序或疗法的人的听觉和/或前庭系统进行研究和分析研究。其中包括分枝杆菌感染的氨基糖苷（Holland，Niaid＆Olivier，NHLBI），抗肿瘤化合物（Hassan，NCI），脑肿瘤放射治疗（Warren，NCI）和经颅磁刺激（Hallett＆Damiano，Ninds，Ninds）。 我们在一次专业会议上接受了接受中枢神经系统辐射疗法的儿童的听力和耳声排放的长期监测海报（Stakhovskaya等，2015）。