Clinical Analysis of Disorders of Hearing and Balance

听力和平衡障碍的临床分析

• 批准号: 10003740
• 负责人: Carmen Crowell Brewer
• 金额: $ 147.78万
• 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/10003740
• 关键词: Academy; Acoustic Nerve; Action Potentials; Affect; Age; Algorithms; American; Amikacin; Aminoglycosides; Antineoplastic Agents; Area; Audiology; Auditory; Auditory system; Brain Neoplasms; Characteristics; Classification; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Collaborations; Congenital disorders of glycosylation; Consultations; Cryptococcal Meningitis; Data; Data Collection; Data Set; Development; Diagnostic; Disease; Ear Diseases; Equilibrium; Equipment; Evaluation; Explosion; Exposure to; Familial amyloid nephropathy with urticaria and deafness; Family; Functional disorder; Genotype; Goals; Haplotypes; Head and neck structure; Hearing; Hearing problem; Individual; International; Intervention; Klinefelter' s Syndrome; Laboratories; Loeys-Dietz Syndrome; Magnetic Resonance Imaging; Manuscripts; McCune-Albright Syndrome; Measures; Methodology; Methods; Modality; Monitor; Musculoskeletal Equilibrium; NF1 gene; 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; Neurofibromatosis 1; Neurofibromatosis 2; Noise; Oculocutaneous Albinism; Osteogenesis Imperfecta; Otolaryngology; Parents; Participant; Patients; Persons; Phase; Phenotype; Physiological; Posture; Preparation; Principal Investigator; Protocols documentation; Publishing; Radiation therapy; Reference Values; Relapse; Reporting; Research; Research Design; Research Personnel; Research Support; Rheumatology; Risk; Role; Safety; Schedule; Sex Chromosomes; Siblings; Smith-Lemli-Opitz Syndrome; Societies; Spielmeyer-Vogt Disease; Spinocerebellar Ataxias; Stimulus; Supraoptic Vertical Ophthalmoplegia; System; Testing; Time; Transcranial magnetic stimulation; Trauma; Traumatic Brain Injury; United States National Institutes of Health; Usher Syndrome; Variant; Vestibular Aqueduct; Vision; Von Hippel-Lindau Syndrome; WHIM syndrome; Walkers; Work; Xeroderma Pigmentosum; Zein; anakinra; autoinflammatory; base; college; computerized; design; experience; healthy volunteer; hearing impairment; hereditary hearing loss; hydroxypropyl-beta-cyclodextrin; improved; interest; ketotic hyperglycinemia; malformation; meetings; methylmalonic aciduria; otoacoustic emission; ototoxicity; ototoxin; posters; proband; programs; research clinical testing; research study; sex; skills; symposium

1. The Audiology Unit continued our protocol designed to develop normative data for various aspects of auditory and vestibular function. This data is used to establish normal reference ranges for test interpretation 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, test equipment, and subject characteristics (e.g., age, sex) on normal function, and are evaluating variability of auditory and vestibular measures over time. During this past year we conducted a study examining the algorithms used to interpret postural stability on Computerized Platform Posturography. This work will be presented at a national meeting in Spring 2020 and we are currently working on manuscript development (Wafa et al.). Additionally, we published a manuscript based on earlier work that compared methods for quantifying utricular function (Zalewski et al., 2018). 2. In collaboration with other NIH investigators (NHLBI, NIAID and NCI), we continue our comprehensive monitoring program for persons participating in clinical trials in which there may be risk of ototoxic hearing loss. These include aminoglycosides, anti-neoplastic compounds, and radiation therapy for brain tumors. In concert with our focus on ototoxicity, we published an article (Brewer & King, 2018) on ototoxicity grading scales, and co-edited (Brewer & Boudin, 2018) a special edition of the International J. of Audiology devoted to the topic of clinical ototoxicity monitoring. We presented a poster on amikacin ototoxicity at the American Auditory Society meeting (Chisholm et al., 2019) and are scheduled to present additional work in this area at an upcoming conference (NCRAR). 3. We designed and completed a test protocol to determine the stability of the auditory nerve action potential and otoacoustic emissions in a group of healthy volunteers. The goals were to determine feasibility of these physiologic measures as markers of damage to the auditory system from noise or ototoxic agents (Bieber et al., manuscript in submission) 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). We contributed to a manuscript that includes hearing safety data (Moehlman et al, 2019). 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 are co-authors on a manuscript examining the influence of the SLC26A4 haplotype on the phenotype of persons with EVA (Chao et al., 2019). 5. In collaboration with Dr. Williamson (NIAID), we have evaluated and characterized auditory function in a group of previously healthy patients with cryptococcal meningitis (King et al., 2019). 6. In collaboration with Dr. Porter (NICHD), we continue participation in a phase 2/3a-c trial of hydroxypropyl beta cyclodextrin for treatment of Niemann Pick type C disease. Our roles included auditory monitoring, ototoxicity grading, and reporting to FDA and safety monitors. 7. In collaboration with (Porter, NICHD) we have examined auditory function in patients with Smith-Lemli-Opitz syndrome. A manuscript is being developed (Zalewski et al., in preparation). 8. We are conducting a detailed cross-sectional and longitudinal examination of hereditary hearing loss and auditory function in persons with neurofibromatosis type I (NF1) (Widemann, NCI). This work was presented at the ASHA meeting in November 2018 and a manuscript is being developed (Idowu et al., in preparation). 9. In collaboration with Dr. McDermott (NIAID), we analyzed auditory function in persons with WHIM syndrome; this work was presented at the AA0-HNS meeting in October 2018 (Rieger et al.). 10. 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 two manuscript in preparation: one that details comprehensive balance function in the three types of Usher syndrome. (Wafa et al.) and another that reviews the classification of atypical Usher syndrome (Zein et al.). 11. In collaboration with Dr. Goldbach-Mansky (NIAMS) we continue auditory evaluation of patients with autoinflammatory disorders, including Muckle Wells syndrome and neonatal onset autoinflammatory disorder (NOMID). We have completed gathering data at a 10-year time point post initiation of treatment with anakinra in a large group of patients with NOMID. A poster will be presented at the American College of Rheumatology (Alehashemi et al.) and manuscript is in preparation. 12. In collaboration with Dr. Heiss, we have examined vestibular function in persons with Chiari malformation and presented this work at the American Academy of Audiology meeting in March 2019 (Famili et al.). 13. In collaboration with Dr. Venditti, we have extensively examined the auditory phenotype of persons with methylmalonic acidemia and have a manuscript in development (Zalewski et al., in preparation) 14. In collaboration with Dr. Chittiboina (NINDS), we continue examination of auditory and vestibular function and longitudinal progression in patients with neurofibromatosis type 2 (NF2), a cause of hereditary hearing loss. We have a manuscript in development examining the ability of MRI to predict hearing loss in persons with NF2 (Walker et al., in preparation) 15. In addition to the areas listed above, the Audiology Unit participates in a number of research protocols in which we are conducting deep phenotyping of the auditory and vestibular systems. We are interested in the natural history of hearing loss and vestibular dysfunction, and relationships to other aspects of the disease/disorder and genotype. Our current areas of study include Batten disease/CLN3 (Dang Do, NICHD), congenital disorders of glycosylation (Wolfe & Gahl, NHGRI), gangliosidosis types 1 and 2 (Tifft, NHGRI), GATA2 (Holland, NIAID), hypogonadotropic hypogonadism (Freedman-Delaney, NICHD), Loeys Dietz syndrome (Guerrerio, NIAID), McCune Albright Syndrome (Boyce, NIDCR), oculocutaneous albinism (Adams, NHGRI), osteogenesis imperfecta (Marini, NICHD), propionic acidemia (Venditti, NHGRI), relapsing polychrondritis (Colbert, NIAID), spinocerebellar ataxia (SCA7) (Huryn, NEI), sex-chromosome variants (Muenke, NHGRI), von Hippel-Lindau disease (Heiss, NINDS), and xeroderma pigmentosum (Kraemer & Digiovanna, NCI). 16. We are examining auditory and vestibular function in patients who have experienced potential trauma to the auditory and vestibular systems, including repeated breacher explosions (Wasserman & LoPresti, NINDS; poster presented at Walter Reed conference) and traumatic brain injury (Chan, CC). 17. We contribute to the clinical characterization of auditory function, as indicated by presentation, of participants in the Undiagnosed Diseases Program (Gahl, NHGRI) and provide supportive clinical consultations to patients participating in multiple other protocols at the NIH Clinical Center.

1. 听力学单位继续我们的协议，旨在开发听觉和前庭功能各个方面的规范数据。该数据用于建立测试解释和控制数据的正常参考范围，以便与我们合作研究中不同患者组获得的结果进行比较。我们还在研究各种方法、刺激特征、测试设备和受试者特征（例如年龄、性别）对正常功能的影响，并评估听觉和前庭测量随时间的变化。在过去的一年中，我们进行了一项研究，检查用于解释计算机平台姿势描记术中姿势稳定性的算法。这项工作将在 2020 年春季的全国会议上展示，我们目前正在致力于手稿开发（Wafa 等人）。此外，我们根据早期工作发表了一份手稿，比较了量化椭圆囊功能的方法（Zalewski 等人，2018）。 2. 与其他 NIH 研究人员（NHLBI、NIAID 和 NCI）合作，我们继续对参与可能存在耳毒性听力损失风险的临床试验的人员实施全面监测计划。这些包括氨基糖苷类、抗肿瘤化合物和脑肿瘤的放射治疗。为了配合我们对耳毒性的关注，我们发表了一篇关于耳毒性分级量表的文章（Brewer & King，2018），并共同编辑了（Brewer & Boudin，2018）国际听力学杂志的特别版，专门讨论以下主题：临床耳毒性监测。我们在美国听觉学会会议（Chisholm 等人，2019 年）上展示了阿米卡星耳毒性的海报，并计划在即将举行的会议 (NCRAR) 上展示该领域的其他工作。 3. 我们设计并完成了一个测试方案，以确定一组健康志愿者的听神经动作电位和耳声发射的稳定性。目标是确定这些生理措施作为噪音或耳毒性物质对听觉系统损害的标志的可行性（Bieber 等人，提交的手稿），并确定长期暴露于 MRI 噪音后的听力安全性，同时使用听力保护来支持博士正在进行的研究。杜恩和皮基奥尼 (NINDS)。我们撰写了一份包含听力安全数据的手稿（Moehlman 等人，2019）。 4. 与 Griffith 博士 (NIDCD) 合作，我们继续对前庭导水管扩大 (EVA) 的个体及其兄弟姐妹和父母进行听觉和前庭表型评估。迄今为止，已有100多名先证者及其家人的身份得到确定。我们是一篇手稿的共同作者，该手稿研究了 SLC26A4 单倍型对 EVA 患者表型的影响（Chao 等人，2019）。 5. 我们与 Williamson 博士 (NIAID) 合作，对一组先前健康的隐球菌性脑膜炎患者的听觉功能进行了评估和特征分析 (King et al., 2019)。 6. 我们与 Porter 博士 (NICHD) 合作，继续参与羟丙基 β 环糊精治疗 C 型尼曼皮克病的 2/3a-c 期试验。我们的职责包括听觉监测、耳毒性分级以及向 FDA 和安全监察员报告。 7. 我们与（Porter、NICHD）合作检查了 Smith-Lemli-Opitz 综合征患者的听觉功能。一份手稿正在编写中（Zalewski 等人，正在准备中）。 8. 我们正在对 I 型神经纤维瘤病 (NF1) 患者的遗传性听力损失和听觉功能进行详细的横断面和纵向检查（Widemann，NCI）。这项工作已在 2018 年 11 月的 ASHA 会议上提出，手稿正在编写中（Idowu 等人，正在准备中）。 9. 我们与 McDermott 博士 (NIAID) 合作，分析了 WHIM 综合征患者的听觉功能；这项工作已在 2018 年 10 月的 AA0-HNS 会议上提出（Rieger 等人）。 10. 与博士合作。 Friedman & Griffith (NIDCD) 和 Zein 博士 (NEI)，我们继续研究亚瑟综合症患者的听力和平衡功能。我们对姿势平衡技能及其与前庭和视觉功能、亚瑟综合征类型、基因型以及这些技能随时间的进展/下降的关系感兴趣。我们正在准备两份手稿：一份详细介绍了三种亚瑟综合症的综合平衡功能。 （Wafa 等人）和另一篇评论非典型 Usher 综合征的分类（Zein 等人）。 11. 我们与 Goldbach-Mansky 博士 (NIAMS) 合作，继续对患有自身炎症性疾病的患者进行听觉评估，包括 Muckle Wells 综合征和新生儿发病的自身炎症性疾病 (NOMID)。我们已经完成了对一大群 NOMID 患者开始阿那白滞素治疗后 10 年时间点的数据收集。 海报将在美国风湿病学会（Alehashemi 等人）发布，手稿正在准备中。 12. 我们与 Heiss 博士合作，检查了 Chiari 畸形患者的前庭功能，并在 2019 年 3 月的美国听力学会会议上介绍了这项工作（Famili 等人）。 13. 与 Venditti 博士合作，我们广泛检查了甲基丙二酸血症患者的听觉表型，并正在编写一份手稿（Zalewski 等人，正在准备中） 14. 我们与 Chittiboina 博士 (NINDS) 合作，继续检查 2 型神经纤维瘤病 (NF2)（遗传性听力损失的一种原因）患者的听觉和前庭功能以及纵向进展。我们正在开发一份手稿，检查 MRI 预测 NF2 患者听力损失的能力（Walker 等人，正在准备中） 15. 除了上面列出的领域外，听力学单位还参与了一些研究方案，在这些方案中我们对听觉和前庭系统进行深度表型分析。 我们对听力损失和前庭功能障碍的自然史以及与疾病/紊乱和基因型的其他方面的关系感兴趣。我们目前的研究领域包括 Batten 病/CLN3（Dang Do，NICHD）、先天性糖基化障碍（Wolfe & Gahl，NHGRI）、神经节苷脂沉积症 1 型和 2 型（Tifft，NHGRI）、GATA2（Holland，NIAID）、低促性腺激素性性腺功能减退症（ Freedman-Delaney，NICHD），Loeys Dietz 综合征（Guerrerio， NIAID)、麦库尼奥尔布赖特综合征 (Boyce, NIDCR)、眼皮肤白化病 (Adams, NHGRI)、成骨不全症 (Marini, NICHD)、丙酸血症 (Venditti, NHGRI)、复发性多软骨炎 (Colbert, NIAID)、脊髓小脑共济失调 (SCA7) Huryn，NEI），性染色体变异（Muenke，NHGRI）、von Hippel-Lindau 病（Heiss，NINDS）和色素性干皮病（Kraemer & Digiovanna，NCI）。 16. 我们正在检查那些经历过听觉和前庭系统潜在创伤的患者的听觉和前庭功能，包括反复的破坏者爆炸（Wasserman & LoPresti，NINDS；在沃尔特·里德会议上展示的海报）和创伤性脑损伤（Chan，CC） 。 17. 我们致力于未确诊疾病计划（Gahl，NHGRI）参与者的听觉功能的临床特征（如演示所示），并为参与 NIH 临床中心多个其他方案的患者提供支持性临床咨询。