Deep phenotyping in blepharospasm

项目摘要 肌张力障碍是一组以过度的不随意肌肉收缩为特征的疾病， 痉挛和异常运动。身体的任何部位都可能受到影响。其中最常见的影响 区域是上面部，导致眼睑痉挛（BL）。患者经历了许多不同的，但 重叠的问题，包括眼睛周围的肌肉痉挛，过度眨眼，眼睑颤动， 眼睑张开受损，并扩散到下面部或下颌。传统上，BL被视为相对 同质性疾病，仅严重程度不同。然而，越来越多的证据表明，BL不是 一种同质的紊乱例如，最近的聚类分析包括大量的患者， 为表型不同的亚组提供了证据。在临床上，一段时间以来人们已经认识到， BL的某些亚型比其它亚型更难治疗。也有证据表明， BL具有不同的致病机制。因此，已经有强有力的证据表明病因异质性。 尽管这些不同的临床表现的重要性，有没有工具来区分和 测量它们。未来BL的临床和科学研究需要更复杂的工具来区分 BL的不同表型元件。这些工具是改善疾病诊断和治疗的基本需求。 BL的不同亚型，以监测BL临床试验的结果，并提供更丰富和更 有意义的表型数据支持BL的病理生理基础的研究。的研究 该提案描述了一种新的简单临床评定量表的开发， BL在临床上的特点，一种新颖的不显眼的可穿戴设备，用于严格的区分和量化 这些特征，以及对该疾病的潜在血液生物标志物的初步表征。

PROJECT SUMMARY The dystonias are a group of disorders characterized by excessive involuntary muscle contractions leading to spasms and abnormal movements. Any region of the body may be affected. One of the most commonly affected regions is the upper face, leading to blepharospasm (BL). Patients experience a number of distinct but overlapping problems that include spasms of the muscles around the eyes, excessive blinking, eyelid fluttering, impaired eyelid opening, and spread to the lower face or jaw. Traditionally, BL has been viewed as a relatively homogeneous disorder, differing only in grades of severity. However, there is increasing evidence that BL is not a homogeneous disorder. For example, recent cluster analyses including large numbers of patients have provided evidence for phenotypically distinct subgroups. Clinically, it has been recognized for some time that some subtypes of BL are more difficult to treat than others. There also is evidence that the core symptoms of BL have different pathogenic mechanisms. Thus, there already is strong evidence for etiological heterogeneity. Despite the importance of these different clinical manifestations, there are no tools for distinguishing and measuring them. Future clinical and scientific studies of BL require more sophisticated tools to discriminate the distinct phenotypic elements of BL. These tools are fundamental needs to improve diagnosis and treatment of the different subtypes of BL, to monitor outcomes of clinical trials for BL, and to provide richer and more meaningful phenotypic data in in support of studies of the pathophysiologic underpinnings of BL. The studies of this proposal describe the development of a novel simple clinical rating scale to separately quantify the distinct features of BL in the clinic, a novel an unobtrusive wearable device for rigorous discrimination and quantification of these features, and preliminary characterization of potential blood-based biomarkers for the disorder.