Bringing Order to the Twists and Turns of Dystonia

This editorial comments on the Research Article by Sasikumar et al., which appeared in a recent issue of the journal.

“When I use a word,” Humpty Dumpty said in rather a scornful tone, “it means just what I choose it to mean — neither more nor less.”

“The question is,” said Alice, “whether you can make words mean so many different things.”

Through the Looking Glass, Lewis Carroll

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.1 Before that, the previously accepted definition had not been updated since 1984 and classification scheme since 1998.2

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.3 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 2013.4 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 long‐term 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.5, 6

Finally, the value of a classification system is not contained in its words, but the meaning of those words, and whether those meanings help to disentangle a complex topic by allowing clinicians or researchers to identify patterns or groupings that are biologically meaningful. Possible shortcomings in the 2013 classification have been raised in a recent pilot study by van Egmond and colleagues,7 who found poor inter‐rater agreement between pairs of experienced clinicians asked to extract Axis I (clinical) criteria from written case vignettes. However, although the findings might have been attributed to ambiguities in the classification system, it is also possible that the poor agreement observed between clinicians was more to do with the methodology used to test it. Nevertheless, their suggestion of training programs and panel ratings to improve reproducibility of use of the new classification system will help to improve or refine its structure. Referring to the quote above, Humpty Dumpty makes a valid assertion, but also needs to provide a convincing affirmative response to Alice's question.

Disclosures

Ethical Compliance Statement: Neither informed patient consent nor institutional review board approval was necessary for this work. I confirm that I have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: The author reports no sources of funding and no conflicts of interest.

Financial Disclosures for previous 12 months: The author declares that there are no disclosures to report.