Essential pitfalls in "essential" tremor

Abstract

Although essential tremor has been considered the most common movement disorder, it has largely remained a diagnosis of exclusion: many tremor and nontremor features must be absent for the clinical diagnosis to stand. The clinical features of "essential tremor" overlap with or may be part of other tremor disorders and, not surprisingly, this prevalent familial disorder has remained without a gene identified, without a consistent natural history, and without an acceptable pathology or pathophysiologic underpinning. The collective evidence suggests that under the rubric of essential tremor there exists multiple unique diseases, some of which represent cerebellar dysfunction, but for which there is no intrinsic "essence" other than a common oscillatory behavior on posture and action. One approach may be to use the term essential tremor only as a transitional node in the deep phenotyping of tremor disorders based on historical, phenomenological, and neurophysiological features to facilitate its etiologic diagnosis or serve for future gene- and biomarker-discovery efforts. This approach deemphasizes essential tremor as a diagnostic entity and facilitates the understanding of the underlying disorders to develop biologically tailored diagnostic and therapeutic strategies. © 2017 International Parkinson and Movement Disorder Society.

Keywords: biomarkers; essential tremor; nomenclature; tremor.

Figure 1. Models of tremor

ET has been viewed as a single but heterogeneous disorder (A, model adapted from Louis et al) and as an “isolated action tremor syndrome” encompassing other movement disorders (B; accounting for cases where “classic ET is too narrowly defined”). An alternative model (C, brought to the fore in the reclassification effort for dystonia) relies on the phenomenological characterization of tremor as a movement presented in isolation or in combination with other movement disorders. ET: essential tremor, BTP: benign tremulous parkinsonism; DIP: drug-induced parkinsonism; DYT: designation for genes associated with dystonia; PD; Parkinson disease; FXTAS: Fragile X tremor ataxia syndrome; SCA: spinocerebellar ataxia

Figure 2. Approach to tremor

Historical (shades of red) and clinical features of isolated (upper box) or combined tremor (lower box) serve to provide the foundations on which the etiologic diagnosis (shades of green) can be formulated. The phenomenological clues and etiologic considerations stemming from them are similar to those used in the recent redefinition of dystonia.