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）和配音震颤（VT）是高动神经系统疾病 损害语音和语音生产，并对患者的生活质量产生负面影响，延伸 言语运动的改变，经常导致职业残疾和终身社会隔离。标准 尚未建立对LD和VT的临床护理；也就是说，差异诊断标准仍然是投票， 导致高诊断率很高，而治疗在很大程度上仅限于临时症状管理 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 这些患者的临床护理是对它们独特的临床特征和中性的有限理解 病理生理学。我们提出了一个多机构的跨学科中心研究计划，将重点放在 LD和VT的独特临床和病理生理特征的描述是为了建立 增强这些疾病的临床管理的基本框架，包括它们的准确性 诊断和特异性疗法。中心研究目标将通过 马萨诸塞州眼睛和耳朵医务室的合作临床研究，马萨诸塞州一般 加州大学旧金山大学医院和犹他大学，其中包括三个中心 项目，一种纳入临床研究和数据科学组成部分的科学核心，以及 行政核心为中心活动提供了整体组织基础架构。总体 该中心的具体目的是（1）表征LD和VT的临床表型； （2）理解 LD和VT中的疾病特异性神经病理生理学； （3）LD和VT中的深脑刺激，（4） 机器学习平台，用于LD和VT的鉴别诊断。我们希望我们的跨学科和 合作中心，涵盖耳鼻喉科，语言病理学，神经病学专业知识， 神经外科手术，脑和喉成像，侵入性神经生理学以及临床神经科学并应用 这些领域的完全多模式方法将对 发展有关LD和VT症状学和病理生理学之间联系的新知识， 将有助于定义增强这些疾病的临床护理的新标准。