Essential Tremor Is a Useful Concept: Yes

The term essential tremor (ET) has evolved and changed its meaning over time. Here, I briefly review these developments to make my position understandable: I believe that abandoning the term “essential tremor” will increase rather than reduce the uncertainty around the diagnosis of this large patient group. The introduction of the term ET goes back to 1874,1 but despite important descriptions much earlier,1, 2 ET was firmly established for the first time with the landmark paper by MacDonald Critchley in 1949.3 He carefully described the clinical features of ET, particularly the action tremor of the hands as the main signature, and he noted the rare occurrence of other symptoms, like spasmodic torticollis, choreoathetosis, and “choreiformic twitches.” He also mentioned the hereditary occurrence of ET and reported inconsistent pathology. In his conclusions he was clearly stating that ET has to be separated from the other forms of tremor, in particular he mentioned that senile tremor may be regarded as an old age variant of ET. Concerning other tremors like dystonic and functional tremor he was not yet able to draw conclusions based on the until then existing observations. The next landmark publication was the book by Findley and Capildeo in 1984.4 The separation of ET by Marsden into Type I (benign exaggerated physiologic tremor), Type II (benign pathological ET), Type III (severe pathological ET), and Type IV (symptomatic ET; i.e., tremor with neuropathy, dystonia, Parkinson's disease) is found in that publication and in an additional book chapter.5 Although Marsden distinguished ET from enhanced physiologic tremor, he classified both as variants of ET. In addition he separated different severities of ET. Tremor in dystonia and postural tremor in Parkinson's disease were still seen as possible variants of ET. One important step in the 1970s and 1980s was the delineation of enhanced physiologic tremor, which today we consider one of the most important differential diagnoses. Although there was early mention of an enhanced physiologic tremor,6 this delineation started both with studies of adrenaline-induced tremor7 and with researchers investigating the electrophysiology of tremor and the discharge patterns of single motor units.8, 9 Another source were studies of electromyogram tremor patterns and accelerometry in normal individuals and patients; those studies finally led to the distinction of central and peripheral tremors.10, 11 Focal tremors have always been a matter of debate. They were considered to represent a “forme fruste” of generalized ET or as a form of focal dystonia.12 A related condition is task-specific and position-specific tremor, which also is considered a possible variant of ET.13 The search for the distinction between ET and dystonic tremor has not yet come to a consolidated answer. The term tremor in dystonia was mentioned in the 1930,14 and dystonic tremor has been discussed at least since 1976.15 This started mainly with tremors in spasmodic torticollis—particularly of head15 and hand16, 17 tremors. The first review appeared in 2003.18 Polemic controversy accompanies the development of this term: the largest series of patients with ET published up to 199119 is frequently mentioned. According to Marsden's 1984 classification, they correctly included patients who currently would be classified with dystonic tremor. This article was frequently quoted later as an example in which the criteria for dystonic tremor were not properly applied,20 although it was published 7 years before the first classification appeared in which dystonic tremor was separated from ET.21 There were also positive refinements of the diagnosis of ET. In particular, the article by Bain et al.,22 which presented a new era clinical of assessment of ET based on the former work of Minor,2 Larssen and Sjogren,23 and many others. Bain and colleagues particularly emphasized the bimodal distribution of age at onset and, most important, introduced the quickest and probably most reliable clinical assessment tool for tremor severity: the Archimedes spiral.24 Another important contribution was a plethora of studies outlining the clinical features of ET in much more detail by E.D. Louis and his group.25 In conclusion, the definition of ET changed considerably between 1949 and 2000. The first Movement Disorder Society tremor consensus statement in 199821 summarized these changes by defining ET and, equally important, by defining the many conditions that are no longer considered ET. Those conditions all became entities with inclusion and exclusion criteria, including enhanced physiologic tremor, focal and task-specific tremors, orthostatic tremor, and dystonic tremors. The consensus statement provided the first common framework for tremors and represented the state of the art in 1997. What has happened since the turn of the century, and why is a revision necessary? The clinical picture of ET has become broader; and, although it was considered a monosymptomatic tremor disorder in the past,3 several motor, cognitive, and emotional abnormalities were described. These abnormalities were very mild, could be identified only at a group level, and thus were not discovered before adequately controlled studies were available. Examples of these associated features were cognitive disturbances in elderly patients with ET26-29 and mild cerebellar deficits or cerebellar atrophy in patients with head tremor.30 In addition, some genetic diseases were identified that presented in one or several families with postural tremor.31 Conversely, paraclinical findings of genetics, pathology, imaging, electrophysiology, biochemistry, and epidemiology have revealed interesting new features in different groups of patients with ET; however, to date, all of these biomarkers failed to demonstrate consistent correlations with clinical subgroups of ET or could not be reproduced in other cohorts. The reasons for this lack of success are unknown. We may look for the wrong biomarkers, but it is unlikely that, e.g., genetics will not find convincing answers in an obviously hereditary disease. An important factor may be that major parts of the clinical assessment (e.g., tremor at rest or alcohol sensitivity) are not yet consistently standardized across different research institutions. Such common standards are desperately needed. In addition, paraclinical studies like pathological examinations need common standards.32 There seems to be a consensus around the globe that ET may be a group of diseases with very different etiologies. The strongest argument for different diseases is that, in the majority of patients, we cannot find common genetic abnormalities in an apparently hereditary disease. Thus, ET may have a group of underlying diseases of which we only know a small part. Using the term “primary” or “essential” for well-known diseases with unknown etiology is not uncommon in medicine. Essential hypertonus is the classical example: These patients share the common symptom of abnormally increased blood pressure, and they must have received a complete and negative workup for underlying etiologies. Every physician knows that there must be causes for the symptom that nevertheless are currently unknown or cannot be diagnosed. This is exactly the situation for the large group of patients with ET. They share the clinical feature of bilateral hand tremor and possibly additional local tremor manifestations. The disease is mostly hereditary and may or may not be sensitive to alcohol. There is one important addition to the new classification reflecting the progress that has been made. There are patients who expose further soft signs of unknown significance (slight tandem gait abnormalities, abnormal postures not diagnosed as dystonia, mild cognitive impairment…). Tremor in these patients is now called “ET plus” to indicate that follow-up assessments may are needed.33 Why should we leave a concept that has proven to be clinically useful for many decades? Some clinician researchers say that the definition of ET has not been successful in identifying genes or developing therapies. They erroneously conclude that the definition must be wrong. Here, the “donkey gets the punches instead of the owner.” A classification reflects the current state of the art and can be no better than the science behind it. In my view, the real problem is not to look for new names and reclassifications but to strengthen clinical research to find better criteria. Honestly, we might conclude in a few years that it is impossible to separate different subgroups of ET on the basis of clinical criteria alone. We may instead need biochemical, pathologic and neurophysiologic tools. Another line of thinking should consider the consequences of deleting the term ET. How would we then diagnose these patients? Would “bilateral postural and action tremor with slight head tremor and very mild tandem gait abnormalities slowly progressing since 18 years of unknown etiology” be a solution, and would this be an improvement? My answer is a clear “no.” Finally, we should not mix up the needs for research and patient care. When I discussed the possible deletion of the term ET with patient organizations, they strongly opposed it. Clinical care needs a name for the condition of patients, even if the name is only defined as a syndrome. ET is included in the International Classification of Diseases, at least since the Tenth Revision. It is important for patients to have an accepted disease; in addition, also for our discipline, the most frequent tremor disorder must be represented in this internationally accepted list of diseases. In conclusion, the term ET is needed. The next step is to define the spectrum of the condition clinically. This will be done in the future in the international consortium, which will work as an ?International Parkinson and Movement Disorder Society Study Group on Tremor’. Ethical Compliance Statement: 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 Conflict of Interest: The author reports no conflicts of interest relevant to this work. Financial Disclosures for the previous 12 months: Günther Deuschl has received lecture fees from Almirall and Novartis and has been serving as a consultant for Boston Scientific. He received royalties from Thieme Publishers. He is a government employee and receives funding through his institution for his research from the German Research Council, the German Ministry of Education and Health and Medtronic.