Next-generation clinical phenotyping and pathophysiology of laryngeal dystonia and voice tremor

喉肌张力障碍和声音震颤的下一代临床表型和病理生理学

• 批准号: 10340118
• 负责人: Kristina Simonyan
• 金额: $ 247.85万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10340118
• 关键词: Address; Affect; Animal Model; Behavioral; Botulinum Toxins; Brain; Brain imaging; California; Characteristics; Clinical; Clinical Data; Clinical Management; Clinical Research; Collaborations; Communication; Complex; Data; Data Science; Deep Brain Stimulation; Development; Diagnosis; Diagnostic; Differential Diagnosis; Disease; Disease Management; Dystonia; Ear; Effectiveness; Epidemiology; Essential Tremor; Eye; Functional disorder; General Hospitals; Goals; Human; Image; Impairment; Infrastructure; Injections; Investigation; Knowledge; Laryngeal muscle structure; Larynx; Life; Link; Machine Learning; Massachusetts; Measures; Methodology; Methods; Mission; Monitor; Motor; Movement Disorders; Neurology; Neurosciences; Occupational; Operative Surgical Procedures; Otolaryngology; Outcome; Patient Care; Patients; Phenotype; Predictive Analytics; Production; Public Health; Quality of life; Recommendation; Records; Research; Research Personnel; San Francisco; Site; Social isolation; Spasm; Spastic Dysphonias; Speech; Speech Acoustics; Speech-Language Pathology; Stratification; Symptoms; Testing; Translating; Treatment Efficacy; Tremor; United States National Institutes of Health; Universities; Utah; Voice; accurate diagnosis; base; clinical care; clinical decision-making; clinical examination; clinical phenotype; disability; early detection biomarkers; effective therapy; improved; multimodality; nervous system disorder; neural circuit; neuroimaging; neurophysiology; neuroregulation; neurosurgery; next generation; novel strategies; phenomenological models; programs; relating to nervous system; repository; research study; symptom management; symptomatology; tool; treatment planning

PROJECT SUMMARY / ABSTRACT Laryngeal dystonia (LD) and voice tremor (VT) are hyperkinetic neurological disorders that significantly impair voice and speech production and negatively impact the patient’s quality of life, extending beyond speech motor alterations and often causing occupational disability and life-long social isolation. The standards of clinical care of LD and VT are not established; that is, the differential diagnostic criteria remain vague, leading to a high rate of misdiagnosis, whereas treatment is largely limited to temporary symptom management with botulinum toxin injections into the affected laryngeal muscles. One of the major causes of suboptimal clinical care of these patients is the limited understanding of their distinct clinical characteristics and neural pathophysiology. We propose a multi-institutional, cross-disciplinary Center research program that will focus on the delineation of unique clinical and pathophysiological features of LD and VT in order to establish the fundamental framework for the enhanced clinical management of these disorders, including their accurate diagnosis and disorder-specific therapies. The Center research goals will be accomplished through collaborative clinical research studies at Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, University of California San Francisco, and University of Utah, which will include three Center Projects, a Scientific Core that incorporates the Clinical Research and Data Science components, and an Administrative Core that provides an overall organizational infrastructure to the Center activities. The overall Specific Aims of this Center will be (1) Characterization of clinical phenotypes of LD and VT; (2) Understanding disorder-specific neural pathophysiology in LD and VT; (3) Deep brain stimulation in LD and VT, and (4) Machine-learning platforms for differential diagnosis of LD and VT. We expect that our cross-disciplinary and collaborative Center, encompassing the expertise in otolaryngology, speech-language pathology, neurology, neurosurgery, brain and larynx imaging, invasive neurophysiology, and clinical neuroscience and applying complementary multimodal methodologies across these fields, will have a significant positive impact on developing new knowledge about the links between symptomatology and pathophysiology of LD and VT, which will help define the new standards of enhanced clinical care of these disorders.

项目摘要/摘要 喉肌张力障碍(LD)和声音震颤(VT)是一种多动神经系统疾病，显著 损害声音和言语的产生，并对患者的生活质量产生负面影响，甚至超出 言语运动改变，经常导致职业残疾和终身社会孤立。标准 尚未建立LD和VT的临床护理标准；即鉴别诊断标准仍然模糊， 导致误诊率高，而治疗在很大程度上仅限于暂时的症状处理 将肉毒杆菌毒素注射到受影响的喉部肌肉中。次优的主要原因之一 对这些患者的临床护理是对其独特的临床特征和神经功能的有限了解 病理生理学。我们提出了一个多机构、跨学科的中心研究计划，将重点放在 描述LD和VT独特的临床和病理生理学特征，以建立 加强对这些疾病的临床管理的基本框架，包括其准确性 诊断和针对障碍的治疗。中心的研究目标将通过以下方式实现 马萨诸塞州综合医院马萨诸塞州眼耳医院的合作临床研究 医院、加州大学旧金山分校和犹他大学，其中将包括三个中心 项目，一个包含临床研究和数据科学组成部分的科学核心，以及一个 为中心活动提供整体组织基础设施的管理核心。整体而言 该中心的具体目标将是(1)LD和VT的临床表型特征；(2)了解 LD和VT的障碍特异性神经病理生理；(3)LD和VT的脑深部刺激；以及(4) 用于LD和VT鉴别诊断的机器学习平台。我们希望我们的跨学科和 协作中心，包括耳鼻喉科、语言病理学、神经病学、 神经外科、脑和喉成像、侵入性神经生理学和临床神经科学及其应用 这些领域的互补多式联运方法，将对以下方面产生重大积极影响 发展关于LD和VT的症状学和病理生理学之间的联系的新知识， 将有助于定义加强这些疾病的临床护理的新标准。