Recent Updates on Essential Tremor

ISSN: 2378-3001 Jamal et al. Int J Neurol Neurother 2019, 6:081 DOI: 10.23937/2378-3001/1410081 International Journal of Volume 6 | Issue 1 Open Access Neurology and Neurotherapy REVIEW ARTICLE Recent Updates on Essential Tremor * Check for Fariha Jamal, MD updates Department of Neurology, School of Medicine, Baylor College of Medicine, Texas, USA *Corresponding author: Fariha Jamal, MD, Assistant Professor, Department of Neurology, School of Medicine, Baylor College of Medicine, Texas, USA ferent opinions and lack of understanding among clini- Abstract cians. Essential Tremor is the most common movement disorder, but many aspects of this common condition are Classification unclear. There have been multiple updates in the field of Essential Tremor in last few years, that has improved our Initial consensus criteria for tremor classification was understanding to some extent. Recently, consensus criteria developed in 1998 by Movement Disorder Society [3]. It for classifying tremor disorders was published. Special was recognized that different controversies exist, and emphasis was on Essential Tremor, to facilitate better phenotyping and understanding of underlying etiology. similar phenotypes can be classified differently based Purpose was to identify homogenous population of different on individual observation [4]. Diagnosis of tremor was tremor syndromes. In addition, recent work focused on based on clinical classification only, as etiologies are un- developing non-motor neuropsychological tests that can clear and multifactorial. Clinical diagnosis was based on be used for Essential Tremor patients. A study used these tests to identify MCI subtypes associated with Essential history and examination. Tremor. Further studies have been conducted to study gait Meaning of Essential Tremor has evolved over time and mood difficulties in Essential Tremor patients. Concept of early and late onset Essential Tremor as distinct clinical [5]. For a long time, it was considered as a “pure trem- entities was not endorsed by recent neuropathological or” with no other neurologic and non-neurologic symp- study. MRI guided focused ultrasound thalamotomy was toms and signs [6]. Presence of other neurologic signs FDA approved for patients with refractory Essential Tremor. virtually excluded ET as a possible diagnosis, but this This review summarizes the recent advances in the field of Essential Tremor. concept is changing rapidly. ET is now considered to be a “syndrome” that can be associated with other symp- Keywords toms [7]. Consensus statement on the classification of Essential Tremor, Classification, Neuropathology, Cognition, tremor was revised and published by the task force on Mortality, Treatment tremor of the International Parkinson and Movement Disorder Society in 2017 [8]. Task force defined tremor Essential Tremor (ET) is the most common move- as an involuntary, rhythmic, oscillatory movement of a ment disorder [1]. Despite its common presence, exact body part. etiology, phenotypic diversity, associated symptoms, clinical course, response to medications and surgery is The proposed classification has two main axes. Axis unclear. The term “Essential Tremor” is widely used in 1 is based on clinical features and Axis 2 is based on eti- neurology and at times diverse types of tremor are la- ology. Axis 1 is quite broad and includes clinical history, belled as ET without clear understanding [2]. Due to lack examination, laboratory tests, receptor imaging, and of understanding, there are concerns for over-diagnosis biomarkers. Clinical features to be considered in axis 1 and possibility of mismanagement. There have been at- include age of onset, family history, temporal evolution, tempts to develop a classification scheme for tremor to exposure to drugs, toxins, body distribution, activation identify different phenotypes, underlying etiology and conditions, frequency and associated signs. Onset after associated neurologic symptoms, but there are still dif- 60 years of age is to be considered as late adulthood. Citation: Jamal F (2019) Recent Updates on Essential Tremor. Int J Neurol Neurother 6:081. doi. org/10.23937/2378-3001/1410081 Accepted: May 08, 2019: Published: May 10, 2019 Copyright: © 2019 Jamal F. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Jamal. Int J Neurol Neurother 2019, 6:081 • Page 1 of 6 • DOI: 10.23937/2378-3001/1410081 ISSN: 2378-3001 No change was proposed in activation conditions. Two lum. Louis, et al. demonstrated increase in number of main activation conditions are rest and action tremor. cerebellar torpedoes in ET patients. In their study, mor- Action tremor includes postural, simple kinetic, inten- phological analysis of the Purkinje cells showed increase tional, task specific and isometric tremor. Based on Axis in dendritic swellings, axonal branching, axonal recur- 1, ET can be classified as Essential Tremor and Essential rent collaterals and terminal sprouting in ET patients as Tremor plus. Essential tremor is defined as bilateral up- compared to healthy controls. per extremity action tremor for at least 3-years dura- On the contrary, another postmortem series demon- tion, with or without tremor in other locations and no strated Lewy bodies in ET brains. These bodies were other neurological signs. ET plus is tremor with similar abundant in locus ceruleus as compared to other brain characteristics but may have additional neurological stem nuclei [19,20]. Nor-epinephrine is the main neu- signs such as impaired tandem gait, memory, dystonia rotransmitter in locus ceruleus (LC). Purkinje cells re- or other mild neurologic signs of unknown significance. ceive projections from LC. Another postmortem study Isolated voice, head, orthostatic, task and position specific tremor are not part of ET syndrome as per new clas- showed intranuclear inclusions in cerebellum [21]. sification scheme. 3-years duration was included to ex- These findings point toward cerebellum as the potential clude the possibility of tremor syndrome evolving into site of neurodegeneration in ET patients. Hence, within another neurodegenerative syndrome. cerebellum, there are heterogenous pathological findings which may explain clinical heterogeneity. Etiology Age of Onset One of the goals of developing this classification system is to help with determination of underlying Another controversy that has arisen in recent years etiologies. For a while, it was considered to be a genetic is to distinguish between ET cases based on age of on- disorder only. But due to phenotypic diversity, it is likely set. Deuschl, et al. proposed in 2014 that tremors occur- that underlying etiology is multifactorial and complex. ring later in life (> 65 years) are not classical ET, rather Not a single gene has been linked to ET with certainty. an age-related tremor (ART). Incidence of ET increases Few genetic loci had been implicated e.g. 3q13, 2p22, with age. A meta-analysis suggested that action tremor 6p23 and other variants as per genome wide association may be seen in 10% of individuals above age 90. They studies but none had been accepted as the final genetic argued that ET is fully penetrant after age 65 years, variable involved in pathogenesis of ET [9-11]. Besides, hence, these patients have ART, a different disease en- disease penetrance is incomplete, even in older age tity as compared to classical ET. Their study suggested group [12]. Like other neurodegenerative disorders, increasingly higher prevalence of ART with older age, there is a possibility that environmental exposure faster progression and association with higher mortality along with genetic predisposition triggers the pathway [22]. A similar study suggested distinction between ear- leading to clinical syndrome. Like genetic etiology, no ly and late-onset tremor [23]. At the same time, Louis, single environmental toxin or exposure had been linked et al. have shown that penetrance of ET is not complete with ET pathogenesis. But, few studies have shown that by the age of 65 years [12]. Hence, there is a possibility toxins impacting cerebellum may be associated with that age of onset and clinical progression is heteroge- increased risk of developing ET. These toxins include neous due to diverse etiology and pathogenesis. In an- harmine, harmane, lead and ethanol abuse [13-15]. other study, Kuo, et al. studied the postmortem changes in cerebellum of ET brains and included young and old Neuropathology onset. 30 ET cases with age of tremor onset < 50 years, There have been diverse opinions about the neuro- 30 ET cases with age of onset > 50 years and 30 controls pathology underlying the genesis of ET. It was postu- were included in the study. They also used alternative lated for a long time that a central oscillator exists and age of onset cut-points, 40 and 60 years. Similar patho- pathology in such oscillator causes ET, though definite logic findings were reported for early onset and late on- evidence to prove this had been lacking. Recently, post- set ET cases, and results stayed the same with all age of mortem studies in ET patients have demonstrated de- onset cut-points. Hence, this study did not support the generative changes in cerebellum. Purkinje cells in cer- earlier hypothesis of ART being a distinct clinic-patho- ebellum have demonstrated signs of injury. Torpedoes logical entity [24]. This is still

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