Bringing Order to the Twists and Turns of Dystonia

In 2013, an update on the definition and classification of dystonia was proposed by a Consensus Committee established under the auspices of the Dystonia Medical Research Foundation, the Dystonia Coalition, and the European Dystonia Cooperation in Science and Technology (COST) Action. Before that, the previously accepted definition had not been updated since 1984 and classification scheme since 1998. It is important to recognize that the old classification system cannot be “translated” into the new system—it is not simply replacement of old words with new words. Rather, the new classification categories have new meanings, which help to resolve inconsistencies or dilemmas posed by the old system. The most important conceptual change contained in the 2013 dystonia classification is the recognition that distinct clinical syndromes do not always link exclusively with distinct etiologies, but, rather, there can be phenotypic and etiological overlap. This parallels the increasing recognition of phenotypic and genotypic overlap in genetically determined disorders—that one phenotype can arise from different genotypes and vice versa—but extends this recognition to sporadic and acquired disorders, as well as disorders with shared pathological findings. Possibly the most common point of confusion between the old and new classification systems is the use of the term “primary” dystonia. This diagnostic term, used in the older classification, implied both that the clinical syndrome was of “pure” dystonia and that there were no obvious neuropathological findings or neurodegeneration. The term is not synonymous with “isolated” dystonia, which in the new classification refers only to the clinical findings. A separate etiological classification term is required if describing a disease etiology, for example, “idiopathic isolated dystonia without pathological abnormalities,” “familial isolated dystonia associated with THAP1 mutations,” or “isolated dystonia due to a neurodegenerative disease” (e.g., glutaric aciduria). In the March issue of Movement Disorders Clinical Practice, Sasikumar and colleagues have systematically reviewed the adoption and accuracy of implementation of the new dystonia classification system in the medical literature since its publication in 2013. Among the almost 1,000 articles included in the study, approximately 60% used the classification correctly, 30% used mixed terminology, and 10% continued to use the old classification. Given the expected lag time between publication and even early adopters, these data can be interpreted as suggesting good acceptance and practical utility of the 2013 classification system, further reflected by an upward trend in the annual rate of correct use. Rate of proper use of the classification was similar in both movement disorder and general neurological journal publications, indicating spread of knowledge of the new classification beyond movement disorder specialists. Articles published in surgical journals were significantly less likely to use the new classification correctly. The authors suggest that part of the explanation may be that prospective studies of surgical therapies designed before 2013, as well as their longterm follow-up publications, often used the term “primary dystonia” in their inclusion criteria to differentiate from and exclude patients with degenerative disease or obvious structural pathology. The new classification will hopefully promote greater clarity in the design of future therapeutic trials, by encouraging researchers to prospectively classify patients according to both their clinical syndrome and etiology, whether sporadic/idiopathic or genotypically characterized. This will allow clearer interpretation of the outcomes in different etiological subgroups and allow subsequent application of precision medicine. As an example, ATP1A3-related disease, like many forms of idiopathic or monogenic dystonia, can present with isolated dystonia and is known to lack evidence of neurodegeneration, yet unlike most other etiologies does not respond to pallidal DBS.