"Essential Tremor Plus": A Problematic Concept: Implications for Clinical and Epidemiological Studies of Essential Tremor.

BACKGROUND: An issue of central importance for most neurological disorders is that of case definition. In the field of neuroepidemiology, case definition informs the design, conduct, and interpretation of research studies that range from observational to interventional studies, from case-control to cohort studies, and from descriptive to analytical studies. For essential tremor (ET), one of the most common neurological disorders, the issue of case definition is particularly important. Though traditionally viewed as a monochromatic disorder, recent years have seen an expansion of the clinical phenotype. In a recently proposed consensus statement on tremor, a proposal was made to separate from ET a new tentatively and uncertainly-defined entity characterized by the presence of additional neurological signs other than action tremor. This entity would be termed "ET-plus". The aims of this invited paper are to discuss the impact of the proposed nomenclature on studies of ET neuroepidemiology.
SUMMARY: The proposed term "ET-plus" is based solely on clinical features and even these are not clearly defined. It is not based on differences in underlying etiology (e.g., genes) or pathology. As such, it is not grounded in underlying biological differences. The use of the term would have numerous research implications. As detailed here, it would greatly complicate or make impossible studies of the descriptive epidemiology of ET, association studies, cohort studies, and clinical trials in ET. Key Messages: The proposed designation has the potential to be very problematic for studies of the epidemiology of tremor. This, along with this questionable validity of the proposed nomenclature, calls its use into serious question.