Deep phenotyping in blepharospasm

项目总结 肌张力障碍是一组以过度的不自主肌肉收缩为特征的疾病，导致 痉挛和异常运动。身体的任何部位都可能受到影响。最常见的影响之一 区域是上面部，导致眼睑痉挛(BL)。患者经历了许多不同的但 重叠问题，包括眼周肌肉痉挛，过度眨眼，眼皮飘动， 眼皮张开受损，并扩散到下面部或下巴。传统上，BL一直被视为一种相对 同质性紊乱，只是严重程度不同。然而，越来越多的证据表明，基本法并不是 一种同质性疾病。例如，包括大量患者在内的最近的集群分析 为表型不同的亚群提供了证据。临床上，一段时间以来，人们已经认识到 BL的某些亚型比其他亚型更难治疗。也有证据表明， BL有不同的致病机制。因此，已经有强有力的证据表明病原学的异质性。 尽管这些不同的临床表现很重要，但没有工具来区分和 测量它们。未来的临床和科学研究需要更复杂的工具来区分 不同的BL表型元素。这些工具是改进诊断和治疗的基本需求 BL的不同亚型，以监测BL的临床试验结果，并提供更丰富和更多的 有意义的表型数据支持对白血病的病理生理基础的研究。的研究 这项建议描述了一种新的简单的临床评定量表的开发，以分别量化不同的 BL在临床上的特点--一种新型的可穿戴设备，用于严格区分和量化 这些特征，以及潜在的血液生物标记物的初步表征。

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.