Clinical Analysis Of Disorders Of Hearing And Balance

听力和平衡障碍的临床分析

• 批准号: 8939469
• 负责人: Carmen Crowell Brewer
• 金额: $ 115.34万
• 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/8939469
• 关键词: Acoustic Neuroma; Affect; Age; Alstrom syndrome; Amikacin; Aminoglycosides; Annual Reports; Antineoplastic Agents; Area; Audiology; Auditory; Brain Neoplasms; Breathing; Characteristics; Child; Clinical; Clinical Protocols; Clinical Research; Collaborations; Collection; Coloboma; Complex; Congenital Disorders; Data; Data Analyses; Data Collection; Data Set; Development; Diagnostic; Disease; 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; Festival; Gangliosidoses; Gender; Genotype; Head and neck structure; Hearing; Heritability; Hospitals; Human; Individual; Inflammatory; Inherited; Institutes; International; Intervention; Laboratories; Lung; Magnetic Resonance Imaging; Manuscripts; McCune-Albright Syndrome; Measures; Methodology; Modality; Molecular Biology; Molecular Genetics; Monitor; Musculoskeletal Equilibrium; Mycobacterium Infections; 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; Newsletter; Oculocutaneous Albinism; Osteogenesis Imperfecta; Otolaryngology; Pancytopenia; Paper; Parents; Participant; 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; Refractory; Registries; Research; Research Design; Research Personnel; Risk; Role; Safety; Sensory; Series; Siblings; Smith Magenis syndrome; Societies; Speech; Stimulus; Stuttering; Syndrome; System; Temporal bone structure; 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; Writing; Xeroderma Pigmentosum; Y Chromosome; Zein; base; clinical Diagnosis; falls; glycosylation; hearing impairment; hydroxypropyl-beta-cyclodextrin; improved; interest; meetings; mouse model; mycobacterial; otoconia; ototoxicity; ototoxin; outcome forecast; posters; proband; programs; research clinical testing; research study; skills; sound

1. We have completed our second year of acquisition of normative data for various aspects of auditory and vestibular function. This data will serve as reference ranges of normal performance by which test results can be interpreted as normal or abnormal, and will be used as control data for the purpose of comparison to data obtained in various patient groups in our collaborative research. We also plan to examine 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 to evaluate intra-subject variability on auditory and vestibular measures. To date we have focused on the development of normative data for tests evaluating otolith function and have made two presentations at professional society meetings on this topic (Zalewski et al. 2014). 2. In collaboration with Drs. Griffith and Friedman (NIDCD), Dr. Moore (Cincinnati Childrens Hospital), and Dr. Zobay (Institute for Hearing Research, UK) we are analyzing data from a series of non-speech tests developed to evaluate sensory/temporal aspects of auditory processing. These tests were administered to twins attending an annual twins festival in an effort to determine heritability of auditory processing skills. We have previously identified heritability of speech-based auditory processing skills and this work extends our research to evaluation of non-speech based skills. We have two manuscripts in preparation. 3. In collaboration with the Molecular Biology and Genetics section (Dr Griffith), the Audiology Unit performs auditory and vestibular phenotypic assessments of individuals with hearing loss and enlarged vestibular aqueducts (EVA), as well as their siblings and parents. Over 90 probands and their families have now been ascertained. The audiology unit continues to evaluate details of the vestibular and auditory phenotype to search for features that predict genotype, clinical prognosis, or clinical diagnosis. We contributed to two manuscripts since that last annual report (Chattaraj et al. Sept 2013, and Chien et al, submitted). 4. In collaboration with Drs. Friedman and Griffith of the NIDCD and Dr. Zein (NEI), the Audiology Unit continues to evaluate 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, and the progression of these skills over time. We have contributed to one manuscript in 2014 (Zein et al., in submission) and presented a poster at the NIH Research Festival in October 2013 (Wafa et al.). 5. In collaboration with Dr. Drayna (NIDCD), we have prepared an auditory test protocol to investigate a group of participants with stuttering. 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 Dr. Forbes D. Porter (NICHD), we participated in a phase 1 trial of Hydroxypropyl beta cyclodextrin for treatment of Neimann Pick Type C (NPC) disease. Our roles include monitoring and grading of auditory function, participation on the safety committee, and participation in the NIH/NCATS NPC Ototoxicity Meeting and other discussions regarding this treatment. Additionally, we published two papers on the auditory phenotype of NPC, one in the mouse model (King et al., 2014) and one in humans (King et al., 2014). 8. In collaboration with Dr. Raphaela 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. This work resulted in one publication in the past year (Sibley et al., 2014). 9. In collaboration with Dr. Brian Brooks (NEI) we evaluated auditory function in persons with coloboma. This work has contributed to one manuscript (Huynh et al., Dec 2013). I0. In collaboration with Dr. Stephen Holland, (NIAID) we collected research data and contributed to manuscripts evaluating the auditory phenotypes of GATA2 (Spinner et al., 2014) and the auditory and vestibular phenotypes of GATA3 (Chien et al., 2014). 11. In collaboration with Drs. Kenneth Olivier and Stephen Holland (NIAID) we conducted auditory evaluations and contributed to a manuscript on the use of inhaled amikacin for refractory pulmonary nontuberculosis mycobacterial disease (Olivier et al, 2014). 13. In collaboration with Dr. Meral Gunay-Aygun (NHGRI) we evaluated auditory function, including evoked potentials, in patients with Alstrom syndrome and presented a poster on this topic at a professional society meeting (Brewer et al. 2014). 14. In collaboration with Dr. Charles Venditti (NHGRI) we evaluated and analyzed the natural history of auditory function in patients with methylmelonic acidemia. This resulted in a poster presentation (Nast et al., 2014) at a professional society meeting. 15. In collaboration with investigators from other NIH institutes, we are evaluating hearing, electrophysiologic auditory function, and central auditory processing manifestations in persons oculocutaneous albinism (Dr. Adams, NHGRI), neurofibromatosis type I (Dr. Widemann, NCI), Congenital Disorders of Glycosylation (Dr. Gahl, NHGRI), gangliosidosis types 1 and 2 (Dr. 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 presented a poster at professional society meeting on the topic of GM1 (King et al. 2014). 16. In collaboration with Dr. Heiss (NINDS), we are evaluating hearing, electrophysiologic auditory function, vestibular function, and postural balance in persons with neurofibromatosis type 2. We are interested in sensitivity of these assessments in early detection and monitoring of vestibular schwannomas. This work resulted in a publication during 2014 (Holliday et al.). 17. We continue to evaluate natural history of auditory function in persons with Fanconi anemia and other inherited bone marrow failure syndromes (IBMFS) (Dr. Alter, NCI), McCune-Albright syndrome and polyostotic fibrous dysplasia (Dr. M. Collins, NIDCR), von Hippel-Lindau disease (Lonser, NINDS), Smith-Magenis syndrome (Ms. Smith, NHGRI), WHIMS (Dr. McDermott, NIAID), osteogenesis imperfecta (Dr. Marini, NICHD), Y-Chromosome variants (Dr. Muenke, NHGRI), xeroderma pigmentosum and trichothiodystrophy (Drs. Kraemer and Digiovanna) and the Undiagnosed Diseases Program (Dr. Gahl, NHGRI). We are interested in the auditory phenotype, natural history of hearing, and relationships to other aspects of disease/disorder and genotype. We wrote a newsletter article (Temporal Bone Registry Newsletter) on the otopathology of xeroderma pigmentosum published in Fall 2013. 18. In collaboration with investigators from other NIH institutes, we are evaluating hearing and vestibular function in persons with exposure to breacher explosions (Drs. Wasserman and LoPresti, NINDS). We are interested in the effects of repeated exposures on the auditory and vestibular systems. 19. In collaboration with investigators from other NIH institutes, we continue to implement and analyze studies of the auditory and/or vestibular system of persons participating in clinical procedures or therapies in which these systems may be at risk. These include aminoglycosides for mycobacterium infections (Drs. Holland and Olivier), antineoplastic compounds (Drs. Gramsa and Hassan, NCI), radiation therapy for brain tumors (Dr. Warren), and transcranial magnetic stimulation (Drs. Hallett and Damiano, NINDS).

1. 我们已经完成了第二年的听觉和前庭功能各方面规范数据的获取。 该数据将作为正常表现的参考范围，通过该范围可以将测试结果解释为正常或异常，并将用作对照数据，以便与我们合作研究中不同患者组获得的数据进行比较。 我们还计划检查各种方法、刺激特征、测试设备、测试范式的影响以及非病理受试者特征（例如年龄、性别）对正常功能的影响，并评估受试者内部对听觉和前庭的变异性措施。 迄今为止，我们的重点是开发评估耳石功能测试的规范数据，并在专业协会会议上就该主题做了两次演讲（Zalewski 等人，2014 年）。 2. 与博士合作。 Griffith 和 Friedman (NIDCD)、Moore 博士（辛辛那提儿童医院）和 Zobay 博士（英国听力研究所）我们正在分析一系列非言语测试的数据，这些测试旨在评估听觉处理的感觉/时间方面。 这些测试是对参加一年一度的双胞胎节的双胞胎进行的，以确定听觉处理技能的遗传性。 我们之前已经确定了基于语音的听觉处理技能的遗传性，这项工作将我们的研究扩展到非基于语音的技能的评估。 我们有两份手稿正在准备中。 3. 听力学科与分子生物学和遗传学科（Griffith 博士）合作，对患有听力损失和前庭导水管扩大 (EVA) 的个体及其兄弟姐妹和父母进行听觉和前庭表型评估。目前已有 90 多名先证者及其家人的身份得到确定。听力学部门继续评估前庭和听觉表型的细节，以寻找预测基因型、临床预后或临床诊断的特征。自上一份年度报告以来，我们撰写了两份手稿（Chattaraj 等人，2013 年 9 月提交，Chien 等人，提交）。 4. 与博士合作。 NIDCD 的 Friedman 和 Griffith 以及听力学部门的 Zein 博士 (NEI) 继续评估亚瑟综合症患者的听觉和平衡功能。 我们对姿势平衡技能及其与前庭和视觉功能的关系、亚瑟综合症的类型以及这些技能随时间的进展感兴趣。 我们于 2014 年撰写了一篇手稿（Zein 等人，已提交），并在 2013 年 10 月的 NIH 研究节上展示了一张海报（Wafa 等人）。 5. 我们与 Drayna 博士 (NIDCD) 合作，准备了一份听觉测试方案来调查一组患有口吃的参与者。 6. 我们与 Cunningham 博士 (NIDCD) 合作，开始制定测试方案，以记录接受耳毒性药物的患者耳保护方法的有效性。 7. 我们与 Forbes D. Porter 博士 (NICHD) 合作，参与了羟丙基 β 环糊精治疗 Neimann Pick C 型 (NPC) 病的 1 期试验。 我们的职责包括听觉功能的监测和分级、参与安全委员会、参加 NIH/NCATS NPC 耳毒性会议以及有关该治疗的其他讨论。 此外，我们还发表了两篇关于 NPC 听觉表型的论文，一篇在小鼠模型中（King et al., 2014），另一篇在人类模型中（King et al., 2014）。 8. 与 Raphaela Goldbach-Mansky 博士 (NIAMS) 合作，我们继续评估新生儿发病的多系统炎症性疾病 (NOMID)、家族性感冒自身炎症综合征和 Muckle-Wells 综合征的听觉表现以及几种药物的有效性疗法。 这项工作在过去一年发表了一篇论文（Sibley 等人，2014 年）。 9. 我们与 Brian Brooks 博士 (NEI) 合作评估了缺损患者的听觉功能。 这项工作促成了一份手稿（Huynh 等人，2013 年 12 月）。 I0。 我们与 Stephen Holland 博士 (NIAID) 合作，收集了研究数据并撰写了评估 GATA2 听觉表型（Spinner 等人，2014）以及 GATA3 听觉和前庭表型（Chien 等人，2014）的手稿。 11. 与博士合作。 Kenneth Olivier 和 Stephen Holland (NIAID) 进行了听觉评估，并撰写了一篇关于使用吸入阿米卡星治疗难治性肺非结核分枝杆菌疾病的手稿（Olivier 等，2014）。 13. 我们与 Meral Gunay-Aygun 博士 (NHGRI) 合作，评估了阿尔斯特罗姆综合征患者的听觉功能，包括诱发电位，并在专业协会会议上展示了有关该主题的海报（Brewer 等人，2014 年）。 14. 我们与 Charles Venditti 博士 (NHGRI) 合作，评估并分析了甲基甜瓜酸血症患者听觉功能的自然史。 这导致在专业协会会议上进行了海报展示（Nast 等人，2014 年）。 15. 与其他 NIH 机构的研究人员合作，我们正在评估眼皮肤白化病（Adams 博士，NHGRI）、I 型神经纤维瘤病（Widemann 博士，NCI）、先天性疾病患者的听力、电生理听觉功能和中枢听觉处理表现。糖基化（Gahl 博士，NHGRI）、1 型和 2 型神经节苷脂沉积症（Gahl 博士）蒂夫特，NHGRI）。 我们对听觉表型感兴趣，包括二分音和其他复杂声音的处理，以及与疾病/紊乱和基因型其他方面的关系。我们在专业协会会议上展示了关于 GM1 主题的海报（King et al. 2014）。 16. 与 Heiss 博士 (NINDS) 合作，我们正在评估 2 型神经纤维瘤病患者的听力、电生理听觉功能、前庭功能和姿势平衡。我们对这些评估在前庭神经鞘瘤早期检测和监测中的敏感性感兴趣。 这项工作于 2014 年发表（Holliday 等人）。 17. 我们继续评估范可尼贫血和其他遗传性骨髓衰竭综合征 (IBMFS)（Alter 博士，NCI）、McCune-Albright 综合征和多骨性纤维异常增殖症（M. Collins 博士，NIDCR）患者的听觉功能自然史）、von Hippel-Lindau 病（Lonser，NINDS）、Smith-Magenis 综合征（Smith 女士，NHGRI）、WHIMS （McDermott 博士，NIAID）、成骨不全症（Marini 博士，NICHD）、Y 染色体变异（Muenke 博士，NHGRI）、着色性干皮病和毛发硫营养不良（Kraemer 和 Digiovanna 博士）以及未确诊疾病计划（Gahl 博士） ，国家人类健康研究所）。 我们对听觉表型、听力自然史以及与疾病/紊乱和基因型其他方面的关系感兴趣。我们撰写了一篇关于着色性干皮病耳病理学的时事通讯文章（颞骨登记时事通讯），于 2013 年秋季发表。 18. 我们与其他 NIH 机构的研究人员合作，正在评估暴露于爆破爆炸的人员的听力和前庭功能（Wasserman 和 LoPresti 博士，NINDS）。 我们感兴趣的是重复暴露对听觉和前庭系统的影响。 19. 我们与其他 NIH 机构的研究人员合作，继续实施和分析参与临床程序或治疗的人员的听觉和/或前庭系统的研究，这些系统可能面临风险。 其中包括用于分枝杆菌感染的氨基糖苷类药物（Holland 和 Olivier 博士）、抗肿瘤化合物（Gramsa 和 Hassan 博士，NCI）、脑肿瘤放射治疗（Warren 博士）和经颅磁刺激（Hallett 和 Damiano 博士，NINDS） 。