The Essential Tremors: Evolving Concepts of a Family of Diseases

Abstract

The past 10 years has seen a remarkable advance in our understanding of the disease traditionally referred to as “essential tremor” (ET). First, the clinical phenotype of ET has been expanded from that of a bland, unidimensional, and monosymptomatic entity to one with a host of heterogeneous features. These features include a broader and more nuanced collection of tremors, non-tremor motor features (e.g., gait abnormalities) and a range of non-motor features, including cognitive, psychiatric, sleep, and other abnormalities. The natural history of these features, as well as their relationships with one another and with disease duration and severity, are better appreciated than they were previously. Studies of disease etiology have identified a number of candidate genes as well as explored several environmental determinants of disease. In addition, the decade has seen the beginnings and expansion of rigorous postmortem studies that have identified and described the postmortem changes in the brains of patients with ET. This emerging science has given rise to a new notion that the disease, in many cases, is one of cerebellar system degeneration. Across all of these studies (clinical, etiological, and pathophysiological) is the observation that there is heterogeneity across patients and that “essential tremor” is likely not a single disease but, rather, a family of diseases. The time has come to use the more appropriate terminology, “the essential tremors,” to fully describe and encapsulate what is now apparent. In this paper, the author will review the clinical, etiological, and pathophysiological findings, referred to above, and make the argument that the terminology should evolve to reflect advances in science and that “the essential tremors” is a more scientifically appropriate term.

Essential Tremor

“…2,6 Because of the marked variability in disease progression and tremor characteristics, and due to the growing evidence for the existence of a repertoire of nonmotor symptoms, ET is now unequivocally recognized as a clinically heterogeneous disease or a family of diseases. 7,8 Hence, for a disease with such phenotypic heterogeneity, an additional diagnostic label ET plus has surfaced several controversies. Moreover, the additional clinical features based on which the term ET plus has emerged are subtle, of unclear clinical significance, and may have interrater variabilities.…”

Graph Theoretical Analysis of Structural Covariance Reveals the Relevance of Visuospatial and Attentional Areas in Essential Tremor Recovery After Stereotactic Radiosurgical Thalamotomy

“…Third, the anatomical underpinnings of ET may bear a subject-specific nature, and hence, may not be adequately captured by a group-level analysis relying on correlations across subjects as deployed here. Along this line of reasoning, it is interesting to notice that essential tremor is, nowadays, considered by many as a family of disparate diseases rather than a single entity ( Jankovic, 2002 ; Elble, 2013 ; Espay et al, 2017 ; Louis, 2021 ).…”

Tremor Syndromes: An Updated Review

“…Before the introduction of the new tremor classification by the IPMDS, ET has been regarded as a "disease" or a "family of diseases" (181,182). However, the new classification describes ET as a tremor "syndrome."…”

“…Before the introduction of the new tremor classification by the IPMDS, ET has been regarded as a “disease” or a “family of diseases” ( 181 , 182 ). However, the new classification describes ET as a tremor “syndrome.” This change has stimulated scientific debates as to whether ET should be regarded as a “disease” or a “syndrome” or whether the various variants of ET should be simply considered subtypes, such as ET-PD, ET-dystonia, ET-ataxia, and other, since one may with time evolve into another ( 10 , 183 – 185 ).…”