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

项目总结/摘要 喉肌张力障碍（LD）和声音震颤（VT）是运动过度的神经系统疾病， 损害声音和言语产生，并对患者的生活质量产生负面影响， 语言运动改变，往往造成职业残疾和终身社会孤立。标准 LD和VT的临床护理尚未建立;也就是说，鉴别诊断标准仍然模糊， 导致高误诊率，而治疗主要限于暂时的症状管理 用肉毒杆菌毒素注射到受影响的喉部肌肉次优的主要原因之一 这些患者的临床护理是有限的了解他们独特的临床特征和神经 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的独特临床和病理生理学特征，以建立 加强这些疾病的临床管理的基本框架，包括其准确的 诊断和疾病特异性治疗。中心的研究目标将通过以下方式实现： 在马萨诸塞州眼耳医院，马萨诸塞州综合医院进行的合作临床研究 医院、加州旧金山弗朗西斯科和犹他州大学，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件的科学核心， 管理核心，为中心活动提供全面的组织基础设施。整体 该中心的具体目标是（1）LD和VT的临床表型表征;（2）了解 LD和VT中的疾病特异性神经病理生理学;（3）LD和VT中的深部脑刺激，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，言语语言病理学，神经学， 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应用 这些领域的互补多模式方法，将产生重大的积极影响， 发展关于LD和VT的病理学和病理生理学之间联系的新知识， 将有助于确定这些疾病的加强临床护理的新标准。

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.