Essential tremor: Is the word “essential” really essential?

Abstract

Essential tremor (ET) is among the common movement disorders. A surge in research in recent years has considerably improved our understanding of disease etiology and pathogenesis, and its associated clinical phenomenology and natural history. With this progress have emerged a multitude of new questions and conundrums and newly proposed terminologies. Amidst these various related discussions, it is worth revisiting the essence of the nomenclature, “essential tremor”, to assess how well it continues to fit the growing understanding of this entity. Here we revisit the historical underpinnings of the nomenclature, its accuracy, pitfalls of eliminating the word, and advantages of removing the word. There are two primary historical bases for using the word “essential”: (i) idiopathic or unclear etiology, (ii) a unitary (single-featured) trait perceived as a constitutional feature. Numerous studies indicate that ET is neither truly idiopathic nor is fully isolated, making the use of “essential” technically incorrect. There are pitfalls and advantages of eliminating the term “essential” and both are succinctly described in this article. Yet in the absence of any flawless alternatives at present, we conclude that it is preferable for now to persist with “essential” tremor, thereby respecting the historical continuity of this one-and-a-half-century old nomenclature.

Introduction:

Essential tremor (ET) is a commonly-encountered neurological disorder that is among the most prevalent movement disorders among adults [1]. A surge in the research in recent years has considerably improved our understanding of disease etiology and pathogenesis, as well as its associated clinical phenomenology and natural history [2]. With this progress in the field has emerged a multitude of new questions and conundrums. Among these is the nomenclature “essential tremor” and is proper characterization and classification. For example, there is discussion as to whether ET should be regarded as a “disease”, “family of diseases”, or a “syndrome”[3], and a newly-proposed term, “ET plus”, suggested by the tremor task force of the International Parkinson and Movement Disorders Society, has also been a matter of ongoing controversy [4,5]. As one might expect, in parallel with these debates on taxonomy are discussions about the utility of the overall concept of “ET” [6,7]. Amidst these various related discussions, it is worth revisiting the essence of the nomenclature, “essential tremor”, to see how well it continues to fit the growing understanding of this entity. ET does not stand alone. Nomenclatural issues not uncommonly face other disease entities, for a variety of reasons, which have included expansion of the clinical phenotype (e.g., “primary biliary cirrhosis” to “primary biliary cholangitis”) [8], socio-political issues (“Hallervorden Spatz disease” to “pantothenate kinase-associated neurodegeneration” [9] and “Reiter syndrome” to “reactive arthritis”) [10], and improved understanding of pathogenesis (“mucocutaneous lymph node syndrome” to “Kawasaki disease”) [11]. ET has not remained free from these sorts of nomenclatural adjustments as there was a suggestion a decade ago to desist from the use of “benign essential tremor” and rather to use “essential tremor” [12]. This was principally driven by the fact that the word “benign” is a misleading label for a chronic progressive disease that often substantially worsens the quality of life of the patients. Furthermore, in common practice and in the literature, the term was being used with less and less frequency.

With this as a backdrop, and in view of progress in our understanding of ET, it would seem to have some value for us to revisit and re-evaluate terminology, as this provides us with an opportunity to think more deeply and more critically about the underlying entity we are struggling to best name – its causes, its characteristics, and its very nature. In this Point of View article, we revisit the word “essential” in “essential tremor”. In doing so, we explore the historical underpinnings of the nomenclature of ET, its accuracy, pitfalls of eliminating the word, and advantages of removing the word. We also consider lessons learned from other illnesses that have used the label “essential”.

Historical underpinnings of the term “essential tremor”:

The use of the word “essential” to denote this type of tremor dates back to 1874, when it was first used by Pietro Burresi, a professor of Medicine at the University of Siena, Italy, who referred to a patient with tremore semplice essenziale [13]. Over the subsequent decade or two, variants of this term were used in the medical literature, with each retaining the word “essential”[13] (Table 1). The authors of these reports highlighted a number of features that helped in its delineation from the other forms of tremor [13]. First, the disorder was often familial but otherwise there was no known proximate cause [13]. The second is that it was viewed as constitutional – a central (i.e., generally present) feature of an individual [13]. Hence, a person had certain fixed properties such as their eye color, a general body form, and a certain emotionality and temperament. As with the tremor of ET, these were often simple, unitary properties. Constitutional conditions were viewed as so firmly fixed within the organized structure of the body that they were an intrinsic or “essential” part of the individual’s physical makeup [13].

Table 1:

History of the nomenclature of essential tremor

Year	Term used	Language	Author*
1874	Tremore semplice essenziale	Italian	Pietro Burresi
1879	Tremore essenziale congenito	Italian	Edoardo Maragliano
1890	Essentieller Tremor	German	Anton Nagy
1892	Tremblement essentiel hereditaire	French	Fulgence Raymond

^*For a link to these papers, please see Louis et al. [13]

The word “essential” (or its translated equivalent) is bolded in each term above.

“Essential tremor” was not unique with respect to the choice of this terminology. Several other diseases were also prefixed by the term “essential”. These include “essential hypertension”, “essential myoclonus” “essential pentosuria”, “essential fruktosuria”, “essential thrombocythemia”, and “essential mixed cryoglobulinemia”. Until the second half the 19^th century, elevated blood pressure was thought to be invariably caused by underlying renal pathologies or arteriosclerosis. Subsequently, several researchers described elevated blood pressure in patients without any apparent renal pathologies [14,15] In 1915, Allbut used the term “hyperpiesis” to describe elevate blood pressure independent of chronic nephritis and arteriosclerosis. However, for unknown reasons “hyperpiesis” did not gain popularity [14]. Around the same period, in 1911, Frank coined the term essentielle hypertonie which survived the test of time to a great extent and subsequently became “essential hypertension” in English [15]. As another example, the first clinical description of myoclonus was by Friedreich in 1881and he coined the term “paramyoclonus multiplex” to describe quick movements, distinct from epilepsy, symmetrically affecting multiple sites of the body [16]. “Paramyoclonus multiplex” was afterwards shortened to the currently used rubric i.e. “myoclonus”. In 1903, Lundborg proposed a classification system (physiologic, “essential”, epileptic, and symptomatic) in which “essential” myoclonus represented the conditions in which myoclonus was not associated with any other recognizable features[16].

Indeed, if one dives more deeply into the meaning of the word “essential”, one sees standard dictionaries link it with two meanings- (i) the widely known meaning- “something of the utmost importance”, and (ii) “idiopathic or self-existing”[17]. Thus, it seems that broadly across the field of medicine, the word “essential” is synonymous with “idiopathic” or “primary”. However, it is not entirely clear why in the late 19^th century, “essential” was preferred over “idiopathic” or “primary” as prefixes for the aforementioned conditions. Perhaps, one of the reasons is that “idiopathic”, having its origin from Greek, was not used much in the modern English literature in the first half of the 20^th century[18].

Is the nomenclature, “essential tremor”, accurate?

If we go by the two primary historical bases for using the word “essential” i.e. (i) idiopathic or unclear etiology, (ii) a unitary (i.e., single-featured) trait perceived as a constitutional feature, the current word “essential” in ET would no longer seem correct. With respect to “idiopathic or unclear etiology”, a slowly growing body of research has identified specific genes within ET families as well as possible environmental contributors to disease etiology [2]. Furthermore, neuroimaging, animal model and human postmortem studies suggest a pathogenesis that is linked to the cerebellum and its circuits and one that some have argued is neurodegenerative [2,19,20]. With respect to “a unitary…trait”, extensive clinical and epidemiological studies have not only revealed an enriched tremor phenomenology but also identified a repertoire of other motor and non-motor features in many patients with ET [2,21]. Hence, expansion of our knowledge calls into question the descriptive accuracy of this somewhat outdated nomenclature. Although it may still be argued that the use of the word “essential” may be valid for a subset of patients in whom there is as yet no identified genetic or environmental etiology, with the passage of time, these cases of “cryptogenic” disease are likely to shrink and shrink, making this designation less and less relevant.

Pitfalls of eliminating “essential” from ET:

Changing nomenclature, in general, is fraught with potential problems. The major problem in changing the name of the disease by eliminating “essential” is that it would lead to a cascade of confusions not only in clinical practice but also in the field of research. Similar concerns have been voiced after introduction of the proposed nomenclature “ET plus” and these numerous issues have been elaborated upon elsewhere [22,23]. The rubric ET has been in use in the medical literature for almost one and a half centuries and it means something to clinicians as a diagnosis and as a disease for which there are biologically targeted pharmacological as well as surgical therapies. A change in the nomenclature would certainly surface confusions to those aspects. If not “essential”, what other terms might be useful - “Primary”, “Idiopathic”? Would the adoption of these nomenclatures be flawless? The answer is “No”. First, they do not encompass what is known about disease etiology and pathogenesis. Second, they would also have negative repercussions on research, as change in nomenclature would create difficult links between future studies and older studies associated with “essential” tremor. This would make future systematic reviews and meta-analysis challenging as literature searches in the future would be heterogeneous and limited.

Advantages of removing “essential” from ET:

Removing “essential” would theoretically pave the path for a more accurate nomenclature as it is a perhaps antiquated term that is no longer technically correct. Moreover, patients who are not familiar with medical rubrics may be uncomfortable or even offended with the word “essential” as there is nothing really essential about “essential” tremor. The word “essential” may sound like a paradox to such patients as deterioration of function due to tremor and emergence of several non-motor symptoms often worsens the overall quality of life in ET patients.

Lessons learned from other fields:

As noted above, ET is not the only disease to incorporate the word “essential”. Others have as well. In some of these contexts, the exact meaning and utility of the word “essential” has been controversial at times. In some cases, its use has waned and in others it has continued. For example, concerns regarding the term “essential” hypertension have been well-articulated and debated in the past [24–26]. In fact, leaders in the field of hypertension voiced their opinion against the use of the term “essential” back in 1980s because of the improvement in the knowledge about the etiopathogenesis [27]. Major publications such as the paper on the recommendation of the joint national committee (JNC-8) have used the term “hypertension” instead of “Essential hypertension” [28]. By contrast, “essential” has also been prefixed for diseases with well-established etiologies and pathogenesis. Essential pentosuria and essential fructosuria are two such conditions which are known to occur because of mutation in DCXR gene [29] and KHK gene [30], respectively. In these two conditions, use of the term “essential” probably signifies lack of symptoms and other associated health conditions. Regardless, the term has persisted for historical reasons. In summary, “essential” has been used in the context of a number of diseases. In some of these instances, the term has been removed and in others, it continues to be used. Factors that have contributed to these decisions include the perceived accuracy of the term in the setting of current scientific knowledge regarding etiology, the clinical complexity of the condition, advocacy from leaders in the field, historical continuity and want of a better term.

Conclusions:

Undoubtedly, the prefix “essential”, in the context of ET, is not flawless. It is perhaps no longer even accurate for the reasons noted above. As we have discussed above, presently there are no alternate terms which would transform this one-and-half century old nomenclature that has stood well against the test of time into an impeccable one. Moreover, as a change in nomenclature of an old disease may impact clinical practice as well as research, it is essential to respect the historical continuity. Labels such as “Parkinson’s disease”, “Huntington’s disease”, and “dystonia” do not encapsulate the clinical features of those diseases or incorporate information about their etiology and pathogenesis; nonetheless, there is a preference for their continued use by the medical community. In the future, studies are warranted to explore the knowledge and attitude of the ET patients, their caregivers, and the support groups towards the “essential” in ET as this could influence future decisions. Future research on the pathogenesis of ET could also inform future attempts to modify its nomenclature.

• Research on essential tremor (ET) has advanced considerably in recent years.

• With this, several conundrums have now arisen regarding disease terminology.

• Here we revisit the historic underpinnings of the nomenclature “essential tremor”.

• We critically discuss pitfalls ad advantages of using the term.

• We conclude that it is preferable for now to persist with “essential” tremor.