The Dystonia Coalition: A Multicenter Network for Clinical and Translational Studies

Abstract

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal postures, repetitive movements, or both. Research in dystonia has been challenged by several factors. First, dystonia is uncommon. Dystonia is not a single disorder but a family of heterogenous disorders with varied clinical manifestations and different causes. The different subtypes may be seen by providers in different clinical specialties including neurology, ophthalmology, otolaryngology, and others. These issues have made it difficult for any single center to recruit large numbers of subjects with specific types of dystonia for research studies in a timely manner. The Dystonia Coalition is a consortium of investigators that was established to address these challenges. Since 2009, the Dystonia Coalition has encouraged collaboration by engaging 56 sites across North America, Europe, Asia, and Australia. Its emphasis on collaboration has facilitated establishment of international consensus for the definition and classification of all dystonias, diagnostic criteria for specific subtypes of dystonia, standardized evaluation strategies, development of clinimetrically sound measurement tools, and large multicenter studies that document the phenotypic heterogeneity and evolution of specific types of dystonia.

Keywords: blepharospasm; cervical dystonia; dystonia; laryngeal dystonia; rare diseases; spasmodic dysphonia; torticollis; writer's cramp.

Figure 1

Dystonia Coalition sites. The main coordinating center is at Emory University (star). Sites responsible for directing large multicenter projects are shown in blue. Green shows sites that recruit patients for various studies or are recipients of Pilot Project grants or Career Awards. Affiliate sites are shown in black, and closed sites are shown in red.

Figure 2

Data collection and sharing. Data for large multicenter projects are organized by individual sites (orange) and collected into a central database for checking, storage, and distribution. All Recruiting Sites (top left) may recruit subjects for the Natural History Project and the Biobank Project. Subgroups of Recruiting Sites are selected to participate in the other large multicenter projects including the Cervical Dystonia Rating Scale Project, The Blepharospasm Diagnosis and Rating Scale Project, the Laryngeal Dystonia Diagnosis and Rating Scale Project, and the Patient-Centered Outcomes Project. The Digital Measures Project analyzes video data collected by all projects. Data submitted to the central database are verified and organized and returned to the sites who manage the large multicenter projects, and are also shared with multiple additional users. For example, Recruiting Sites may request a summary of data they entered. Data are also shared with the National Institutes of Health (NIH) and the Data Management and Coordinating Center (DMCC) of the Rare Diseases Clinical Research Network. Subsets of data are also shared with the National Institute of Neurological Disorders and Stroke (NINDS) Repository at Coriell and with other users by request. DMRF, Dystonia Medial Research Foundation; JMU, James Madison University, RushU, Rush University; UCSD, University of California in San Diego; UNM, University of New Mexico; WashU; Washington University in St. Louis.

Figure 3

Financial structure. The majority of funding comes from the NIH Rare Diseases Clinical Research Network (RDCRN), although some funding and other resources also come from Patient Advocacy Groups. The Administrative Unit at Emory University provides payments by direct subcontracts to sites that organize large international multicenter projects. The Administrative Unit also has a subcontract with the Dystonia Medical Research Foundation (DMRF), which is responsible for disbursing funds on a fee-for-service basis to Recruiting Sites (depending on numbers of subjects recruited), smaller projects (such as Pilot Grant Projects or Career Awards), meetings, consultants, and others. JMU, James Madison University; NIH, National Institutes of Health USA; NINDS, National Institute of Neurological Disorders and Stroke; RushU, Rush University; UCSD, University of California in San Diego; UNM, University of New Mexico; WashU, Washington University in St. Louis.