Recent developments in dystonia

Abstract

Purpose of review The dystonias are a family of related disorders with many different clinical manifestations and causes. This review summarizes recent developments regarding these disorders, focusing mainly on advances with direct clinical relevance from the past two years. Recent findings The dystonias are generally defined by their clinical characteristics, rather than by their underlying genetic or neuropathological defects. The many varied clinical manifestations and causes contribute to the fact that they are one of the most poorly recognized of all movement disorders. A series of recent publications has addressed these issues offering a revised definition and more logical means for classifying the many subtypes. Our understanding of the genetic and neurobiological mechanisms responsible for different types of dystonias also has grown rapidly, creating new opportunities and challenges for diagnosis and identifying increasing numbers of rare subtypes for which specific treatments are available. Summary Recent advances in describing the clinical phenotypes and determining associated genotypes have pointed to the need for new strategies for diagnosis, classification and treatment of the dystonias.

The Burke‐Fahn‐Marsden Dystonia Rating Scale is Age‐Dependent in Healthy Children

“…To our best knowledge, BFMDRS scores have never been studied for potential age‐relatedness in children before. We reasoned that forthcoming insight in potential BFMDRS age dependency could provide information for: (1) reliable longitudinal treatment evaluation in young children (such as for longitudinal dystonia databases and for longitudinal evaluation of innovative therapies (such as deep brain stimulation [DBS]); (2) understanding of dystonia progression in different “age‐of‐onset” groups; and (3) adequate phenotypic discrimination between “immature” and “dystonic” motor patterns for adequate interpretation of next‐generation sequencing (NGS) panels …”

“…Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions, causing abnormal, often repetitive, movements or postures. [1][2][3] The neuroanatomical substrate for dystonia is ascribed to dysfunctional networks of the basal ganglia, cerebellum, thalamus, cerebral cortex, and brainstem. 4 The term early onset dystonia is used to denounce the initiation of dystonia before the twenty-sixth year of life.…”

“…We reasoned that forthcoming insight in potential BFMDRS age dependency could provide information for: (1) reliable longitudinal treatment evaluation in young children (such as for longitudinal dystonia databases and for longitudinal evaluation of innovative therapies (such as deep brain stimulation [DBS]) 24,25 ; (2) understanding of dystonia progression in different "age-of-onset" groups 1 ; and (3) adequate phenotypic discrimination between "immature" and "dystonic" motor patterns for adequate interpretation of next-generation sequencing (NGS) panels. 3,26 Methods Participants After informed consent by the parents and children (when older than 12 years of age), we included a total of 104 healthy children for the investigation of BFMDRS age-relatedness. In the absence of existing quantitative age-related BFMDRS outcomes in children, we based sample size selection on previously published data on interobserver agreement in dystonic children.…”

Clinical and scientific perspectives on movement disorders: Stanley Fahn's contributions

“…Disease-specific treatments are increasing as our understanding of etiology for the combined/complex dystonia syndromes expands. 43,44 In addition to a search for a potentially curable cause of dystonia (eg, Wilson's disease and metabolic, structural, or drug-induced dystonias), children and adolescents (especially those with diurnal variation) should be treated with L-dopa for possible dopa-responsive dystonia. 39 In most dystonia patients, treatment is aimed at symptom reduction rather than neuroprotection.…”

Field synopsis and systematic meta-analyses of genetic association studies in isolated dystonia

“…Genetically, dystonia is a complex disease with the parallel occurrence of forms with and without causative genetic factors. Over the past decades more than two dozen loci have been proposed as monogenic causes of dystonia [1][2][3] and 32 confirmed genes (28 with "DYT" labels) [4,5] have been included in the new list of isolated, combined, and complex hereditary dystonia proposed by the International Parkinson and Movement Disorder Society's (MDS)…”