Clinical Analysis of Disorders of Hearing and Balance

听力和平衡障碍的临床分析

• 批准号: 10248890
• 负责人: Carmen Crowell Brewer
• 金额: $ 142.73万
• 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/10248890
• 关键词: Adult; Affect; Age; Algorithms; American; Amikacin; Aminoglycosides; Antineoplastic Agents; Area; Ataxia; Audiology; Auditory; Brain Neoplasms; Cantor; Characteristics; Child; Cisplatin; Classification; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Cochlea; Collaborations; Congenital disorders of glycosylation; Consultations; Cryptococcal Meningitis; Data; Data Collection; Data Set; Development; Diagnostic; Disease; Ear Diseases; Engineering; Equilibrium; Equipment; Evaluation; Evaluation Research; Explosion; Extramural Activities; Familial amyloid nephropathy with urticaria and deafness; Family; Genotype; Guidelines; Haplotypes; Head and neck structure; Hearing; Hearing problem; International; Intervention; Klinefelter' s Syndrome; Laboratories; Loeys-Dietz Syndrome; Longitudinal Studies; Magnetic Resonance Imaging; Manuscripts; McCune-Albright Syndrome; Measures; Medical Genetics; Medicine; Methodology; Modality; Monitor; Mosaicism; Musculoskeletal Equilibrium; Mutation; 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; Normal Range; Osteogenesis Imperfecta; Otolaryngology; Patients; Persons; Phase; Phenotype; Physiologic pulse; Posture; Preparation; Prevention; Principal Investigator; Protocols documentation; Radiation therapy; Reference Values; Rehabilitation Centers; Relapse; Reporting; Research; Research Design; Research Personnel; Rheumatology; Risk; Role; Safety; Sex Chromosomes; Smith-Lemli-Opitz Syndrome; Societies; Spielmeyer-Vogt Disease; Steroids; Stimulus; Supraoptic Vertical Ophthalmoplegia; Syndrome; System; Testing; Time; Transcranial magnetic stimulation; Translational Research; Trauma; USH2A gene; United States National Academy of Sciences; United States National Institutes of Health; Usher Syndrome; Usher Syndrome Type 2; Variant; Vestibular Aqueduct; Vision; Von Hippel-Lindau Syndrome; Woman; Work; Xeroderma Pigmentosum; Zein; anakinra; auditory processing; auditory rehabilitation; autoinflammation; autoinflammatory; college; design; experience; genetic epidemiology; hearing impairment; hydroxypropyl-beta-cyclodextrin; improved; interest; ketotic hyperglycinemia; malformation; meetings; methylmalonic aciduria; multidisciplinary; otoconia; ototoxicity; ototoxin; posters; programs; research study; sex; skills; symposium

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, 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 presented our work examining algorithms used to interpret postural stability at the American Balance Society meeting and manuscript preparation is underway (Wafa et al.). In addition, we are currently designing a sub-study to define normal ranges and evaluate test-retest reliability for tests of cochlear and otolith function. NIDCD collaborations include work with: * Dr Cunningham in her study examining the effect of statins in prevention of cisplatin ototoxicity (Fernandez et al., in submission) * Dr. Hoa in preparation and design of his translational research protocol that aims to examine characteristics of fluctuating hearing loss. This protocol is in development. * Dr. Chein in development and implementation of his longitudinal protocol examining the time course of hearing loss in patients/families with autosomal dominant nonsyndromic hearing loss (DFNA). * Dr. Griffith (NIDCD) with whom we continued analysis of auditory and vestibular data collected from patients with enlarged vestibular aqueducts. 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). Additional work with Dr. Griffith included collaboration on his studies of NLRP3 and its role in the autoinflammation in the cochlea (Nakanishi et al,2020). Trans-NIH Collaborations With investigators in NHLBI, NIAID and NCI, we continue comprehensive monitoring programs for persons participating in clinical trials in which there may be risk of ototoxicity. These include aminoglycosides, anti-neoplastic compounds, and radiation therapy for brain tumors. We presented a poster on amikacin ototoxicity at a conference on ototoxicity monitoring sponsored by the National Center for Rehabilitative Auditory Research (Chisholm et al., 2019) and currently preparing a manuscript on this topic (Chisholm et al.,in preparation). With Dr. Williamson (NIAID), we evaluated and characterized auditory function in a group of previously healthy patients with cryptococcal meningitis (King et al., 2019) and are currently working on a manuscript examining clinical benefits of pulse-taper steroids in patients with non-HIV cryptococcal meningitis (Anjum et al.,in preparation) With Dr. Porter (NICHD), we continued 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. Additionally, we have worked with Dr. Porter to examine auditory function in patients with Smith-Lemli-Opitz syndrome. A manuscript on this topic is nearing completion (Zalewski et al.,in preparation). We conducted a detailed cross-sectional and longitudinal examination of hearing loss and auditory function in persons with neurofibromatosis type I (NF1)(Widemann, NCI). A manuscript on this topic is nearing completion (Idowu et al.,in preparation). 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, and genotype.We have a manuscript under review that details comprehensive balance function in the three types of Usher syndrome(Wafa et al., in submission) and another that reviews the classification of atypical Usher syndrome (Zein et al., 2020). With Dr. Guerrerio (NIAID), we continue to study auditory function in patients with Loeys Dietz syndrome and have a conference presentation and manuscript in preparation (Jeon et al). 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 anakinra in a large group of patients with NOMID. A poster was presented at the American College of Rheumatology (Alehashemi et al.) and a manuscript is in preparation. With Drs. Heiss & Cantor (NINDS), we examined vestibular function in persons with Chiari malformation. We are currently preparing a manuscript on this topic (Famili et al.). With Dr. Venditti (NHGRI), we examined the auditory phenotype of persons with methylmalonic acidemia and have a prepared a manuscript (Zalewski et al., in preparation). With Dr. Dang Do (NICHD) we participated a longitudinal study of patient with Batten disease/CLN3. A multidisciplinary manuscript is in preparation (Dang Do et al.). With Dr Huryn (NEI), we have contributed to a manuscript reporting the clinical features of Heimler syndrome (Daich Varela, et al., in press). Additionally, we presented the auditory (Brewer et al., 2020) and vestibular (Zalewski et al., 2020) manifestations of patients with spinoecerebellar ataxia type 7 at national meetings (AAS, ABS). With Dr. Muenke (NHGRI), we extensively examined auditory function, including auditory processing, in patients with sex chromosome variants. Our poster describing the auditory phenotype of patients with Klinefelter syndrome was accepted for presentation at the ASHA meeting (Zhang et al., 2020). Other Intramural Collaborations Associate investigator status on the following new protocols that are under review: *Dr. Stewart (NHGRI), Clinical, Genetic and Epidemiologic Study of Children and Adults with RASopathies. *Dr.Dowlett-McElroy (NICHD), Deep Phenotype of Women with Finding of Maternal 45,X Mosaicism Contributed to deep phenotyping protocols examining the natural history of hearing loss and vestibular function, and relationships to other aspects of diseases/disorders and genotype include: NF2 (Chittiboina, NINDS), congenital disorders of glycosylation (Wolfe & Gahl, NHGRI), gangliosidosis types 1 and 2 (Tifft, NHGRI), GATA2 (Holland, NIAID), McCune Albright Syndrome (Boyce, NIDCR), osteogenesis imperfecta (Marini, NICHD), propionic acidemia (Venditti, NHGRI), relapsing polychrondritis (Colbert, NIAID), von Hippel-Lindau disease (Heiss, NINDS), and xeroderma pigmentosum (Kraemer & Digiovanna, NCI). Examined auditory and vestibular function in patients who have experienced potential trauma to the auditory and vestibular systems (Chan, CC) and presented these results to the National Academy of Science, Engineering and Medicine. Contributed to clinical characterization of auditory and vestibular function of patients in the Undiagnosed Diseases Network (Gahl, NHGRI) and provided supportive clinical consultations to patients participating in other protocols at NIH. Intramural-Extramural Collaborations With Drs Carr & Modica (Walter Reed) Wasserman (NINDS), we examined the effect of repeated breacher explosions on the auditory and vestibular systems. A manuscript reporting hearing loss without vestibular manifestations in a group of explosive breachers is under review (Modica et al.). With Drs Duncan (UCSF) & Iannacconne (Duke)and Hufnagel (NEI), Dr. Brewer is examining the audiometric phenotype in a large group of patients with Usher syndrome type 2 caused by mutations in the USH2A gene. With Dr. Hallett (NINDS) and others, participated in development of international safety guidelines for transcranial magnetic stimulation

听力学科继续我们的协议 - 听觉前庭测试的规范值。该协议用于建立正常参考范围和控制数据，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。在过去的一年里，我们在美国平衡协会会议上展示了我们的工作，检查用于解释姿势稳定性的算法，并且手稿准备工作正在进行中（Wafa 等人）。此外，我们目前正在设计一项子研究，以定义正常范围并评估耳蜗和耳石功能测试的重测可靠性。 NIDCD 合作包括： * Cunningham 博士在她的研究中检查了他汀类药物预防顺铂耳毒性的效果（Fernandez 等人，已提交） * Hoa 博士正在准备和设计他的转化研究方案，旨在检查波动性听力损失的特征。该协议正在开发中。 * Chein 博士正在制定和实施他的纵向方案，该方案检查常染色体显性遗传非综合征性听力损失 (DFNA) 患者/家庭的听力损失时间进程。 * Griffith 博士 (NIDCD) 我们继续与他一起分析从前庭导水管扩大的患者收集的听觉和前庭数据。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）。与 Griffith 博士的其他工作包括合作研究 NLRP3 及其在耳蜗自身炎症中的作用 (Nakanishi et al,2020)。 跨 NIH 合作 我们与 NHLBI、NIAID 和 NCI 的研究人员一起，继续对参与可能存在耳毒性风险的临床试验的人员进行全面监测。这些包括氨基糖苷类、抗肿瘤化合物和脑肿瘤的放射治疗。我们在国家康复听觉研究中心主办的耳毒性监测会议上展示了阿米卡星耳毒性的海报（Chisholm 等人，2019 年），目前正在准备有关该主题的手稿（Chisholm 等人，正在准备中）。 我们与 Williamson 博士 (NIAID) 一起评估和表征了一组先前健康的隐球菌性脑膜炎患者的听觉功能（King 等人，2019），目前正在撰写一份手稿，检查脉冲锥度类固醇对非 HIV 隐球菌性脑膜炎患者的临床益处（Anjum 等人，准备中） 我们与 Porter 博士 (NICHD) 一起继续参与羟丙基 β 环糊精治疗 Niemann Pick C 型疾病的 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。此外，我们还与波特博士合作检查史密斯-莱姆利-奥皮茨综合征患者的听觉功能。关于这个主题的手稿即将完成（Zalewski 等人，正在准备中）。 我们对 I 型神经纤维瘤病 (NF1)（Widemann，NCI）患者的听力损失和听觉功能进行了详细的横断面和纵向检查。关于这个主题的手稿即将完成（Idowu 等人，正在准备中）。 与博士。 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、Usher 综合征类型和基因型的关系感兴趣。我们正在审查一份手稿，详细介绍了三种类型 Usher 综合征的综合平衡功能（Wafa 等人，已提交），另一份手稿则审查了非典型 Usher 综合征的分类（Zein 等人，2020）。 我们与 Guerrerio 博士 (NIAID) 一起继续研究 Loeys Dietz 综合征患者的听觉功能，并正在准备会议报告和手稿（Jeon 等人）。 我们与 Goldbach-Mansky 博士 (NIAMS) 一起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。美国风湿病学院（Alehashemi 等人）发布了海报，手稿正在准备中。 与博士。 Heiss & Cantor (NINDS)，我们检查了 Chiari 畸形患者的前庭功能。我们目前正在准备关于这个主题的手稿（Famili 等人）。 我们与 Venditti 博士 (NHGRI) 一起检查了甲基丙二酸血症患者的听觉表型，并准备了一份手稿（Zalewski 等人，正在准备中）。 我们与 Dang Do 博士 (NICHD) 一起参与了一项针对 Batten 病/CLN3 患者的纵向研究。 一份多学科手稿正在准备中（Dang Do 等人）。 我们与 Huryn 博士 (NEI) 一起撰写了一份报告海姆勒综合征临床特征的手稿（Daich Varela 等人，正在出版）。此外，我们还在全国会议（AAS、ABS）上介绍了 7 型脊髓小脑共济失调患者的听觉（Brewer 等，2020）和前庭（Zalewski 等，2020）表现。 我们与 Muenke 博士 (NHGRI) 一起广泛检查了性染色体变异患者的听觉功能，包括听觉处理。我们描述克兰费尔特综合征患者听觉表型的海报被接受在 ASHA 会议上展示（Zhang 等人，2020）。 其他校内合作 以下正在审查的新方案的副研究员身份： *博士。 Stewart (NHGRI)，《患有 RASopathies 的儿童和成人的临床、遗传学和流行病学研究》。 *Dowlett-McElroy 博士 (NICHD)，发现母体 45,X 嵌合体的女性深层表型 有助于深度表型分析方案检查听力损失和前庭功能的自然史，以及与疾病/紊乱和基因型其他方面的关系，包括：NF2（Chittiboina，NINDS），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）、McCune Albright 综合征（Boyce、NIDCR）、成骨不全症（Marini、NICHD）、丙酸血症（Venditti、NHGRI）、复发性多软骨炎（Colbert、NIAID）、von Hippel-Lindau 病（Heiss、NINDS）和色素性干皮病（Kraemer & Digiovanna， 美国国家癌症研究所）。 检查了听觉和前庭系统遭受潜在创伤的患者的听觉和前庭功能（Chan，CC），并将这些结果提交给美国国家科学、工程和医学科学院。 为未确诊疾病网络（Gahl、NHGRI）中患者的听觉和前庭功能的临床特征做出贡献，并为参与 NIH 其他方案的患者提供支持性临床咨询。 校内校外合作 我们与 Carr 博士和 Modica (Walter Reed) Wasserman (NINDS) 博士一起研究了重复的破坏者爆炸对听觉和前庭系统的影响。一份报告在一群爆炸性破坏者中没有前庭表现的听力损失的手稿正在接受审查（Modica 等人）。 Brewer 博士与 Duncan (UCSF) 博士、Iannacconne (杜克大学) 和 Hufnagel (NEI) 博士一起检查一大群由 USH2A 基因突变引起的 2 型 Usher 综合征患者的听力表型。 与Hallett博士（NINDS）等一起参与制定经颅磁刺激国际安全指南