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.