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      Treatment of Essential Tremor: Are there Issues We are Overlooking?

      review-article
      1 , 2 , 3 , 4
      Frontiers in Neurology
      Frontiers Research Foundation
      essential tremor, treatment, clinical, pharmacology

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          Abstract

          Background: Essential tremor (ET) is one of the most common neurological diseases. Although a large number of medications have been tested, there are only two first-line medications, primidone and propranolol, which is a situation that has not changed in approximately 30 years. Several recent reviews have summarized the current pharmacotherapeutic options for ET and the approach to the management of ET patients. Yet there remain a number of important issues, both scientific and clinical, that have not been broached in the literature and that have therapeutic implications. Objectives: To introduce several clinical and scientific issues that have not formally entered the published literature on the treatment of ET. Methods: In September 2011, materials for this article were gathered during a literature search of PubMed using the following terms: ET, clinical, clinical trial, treatment, medications, therapeutics. English-language articles were selected for further review. Results: The paper focuses on several topics that have received scant or no discussion in the published literature on ET therapeutics. These topics are as follows: the nature of the underlying disease pathophysiology, the presence of pathological heterogeneity, the complexity of cellular and neurochemical changes which may be underlying this disorder, the presence of clinical heterogeneity, the selection of treatment endpoints, the effects of diagnostic uncertainty, the presence of cognitive and psychiatric features in ET, the identification of possible modifiable risk factors, and the absence of any neuroprotective therapies. Conclusion: The author has identified several topics that have received scant or no discussion in the published literature on ET therapeutics. Further discussion of the issues raised here may lead to improvements in clinical trial methodologies as well as facilitate the development of fresh approaches to pharmacotherapy.

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          Most cited references106

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          Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee.

          This is a proposal of the Movement Disorder Society for a clinical classification of tremors. The classification is based on the distinction between rest, postural, simple kinetic, and intention tremor (tremor during target-directed movements). Additional data from a medical history and the results of a neurologic examination can be combined into one of the following clinical syndromes defined in this statement: enhanced physiologic tremor, classical essential tremor (ET), primary orthostatic tremor, task- and position-specific tremors, dystonic tremor, tremor in Parkinson's disease (PD), cerebellar tremor, Holmes' tremor, palatal tremor, drug-induced and toxic tremor, tremor in peripheral neuropathies, or psychogenic tremor. Conditions such as asterixis, epilepsia partialis continua, clonus, and rhythmic myoclonus can be misinterpreted as tremor. The features distinguishing these conditions from tremor are described. Controversial issues are outlined in a comment section for each item and thus reflect the open questions that at present cannot be answered on a scientific basis. We hope that this statement provides a basis for better communication among clinicians working in the field and stimulates tremor research.
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            A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor.

            Deep-brain stimulation through an electrode implanted in the thalamus was developed as an alternative to thalamotomy for the treatment of drug-resistant tremor. Stimulation is thought to be as effective as thalamotomy but to have fewer complications. We examined the effects of these two procedures on the functional abilities of patients with drug-resistant tremor due to Parkinson's disease, essential tremor, or multiple sclerosis. Sixty-eight patients (45 with Parkinson's disease, 13 with essential tremor, and 10 with multiple sclerosis) were randomly assigned to undergo thalamotomy or thalamic stimulation. The primary outcome measure was the change in functional abilities six months after surgery, as measured by the Frenchay Activities Index. Scores for this index can range from 0 to 60, with higher scores indicating better function. Secondary outcome measures were the severity of tremor, the number of adverse effects, and patients' assessment of the outcome. Functional status improved more in the thalamic-stimulation group than in the thalamotomy group, as indicated by increases in the score for the Frenchay Activities Index (from 31.4 to 36.3 and from 32.0 to 32.5, respectively; difference between groups, 4.4 points; 95 percent confidence interval, 2.0 to 6.9). After adjustment for base-line characteristics, multivariate analysis also showed that the thalamic-stimulation group had greater improvement (difference between groups, 5.1 points; 95 percent confidence interval, 2.3 to 7.9). Tremor was suppressed completely or almost completely in 27 of 34 patients in the thalamotomy group and in 30 of 33 patients in the thalamic-stimulation group. One patient in the thalamic-stimulation group died perioperatively after an intracerebral hemorrhage. With the exception of this incident, thalamic stimulation was associated with significantly fewer adverse effects than thalamotomy. Functional status was reported as improved by 8 patients in the thalamotomy group, as compared with 18 patients in the thalamic-stimulation group (P=0.01). Thalamic stimulation and thalamotomy are equally effective for the suppression of drug-resistant tremor, but thalamic stimulation has fewer adverse effects and results in a greater improvement in function.
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              Treatment of patients with essential tremor.

              Essential tremor is a common movement disorder. Tremor severity and handicap vary widely, but most patients with essential tremor do not receive a diagnosis and hence are never treated. Furthermore, many patients abandon treatment because of side-effects or poor efficacy. A newly developed algorithm, based on the logarithmic relation between tremor amplitude and clinical tremor ratings, can be used to compare the magnitude of effect of available treatments. Drugs with established efficacy (propranolol and primidone) produce a mean tremor reduction of about 50%. Deep brain stimulation (DBS) in the thalamic nucleus ventrointermedius or neighbouring subthalamic structures reduces tremor by about 90%. However, no controlled trials of DBS have been done, and the best target is still uncertain. Better drugs are needed, and controlled trials are required to determine the safety and efficacy of DBS in the nucleus ventrointermedius and neighbouring subthalamic structures. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Front Neurol
                Front. Neur.
                Frontiers in Neurology
                Frontiers Research Foundation
                1664-2295
                11 November 2011
                13 January 2012
                2011
                : 2
                : 91
                Affiliations
                [1] 1simpleGertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University New York, NY, USA
                [2] 2simpleDepartment of Neurology, College of Physicians and Surgeons, Columbia University New York, NY, USA
                [3] 3simpleTaub Institute for Research on Alzheimer’s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University New York, NY, USA
                [4] 4simpleDepartment of Epidemiology, Mailman School of Public Health, Columbia University New York, NY, USA
                Author notes

                Edited by: Marina Tijssen, Academic Medical Centre, Netherlands

                Reviewed by: Pedro Chana, Universidad de Santiago de Chile, Chile; Bart Post, Radboud University Nijmegen Medical Centre, Netherlands

                *Correspondence: Elan D. Louis, Unit 198, Neurological Institute of New York, 710 West 168th Street, New York, NY 10032, USA. e-mail: EDL2@ 123456columbia.edu

                This article was submitted to Frontiers in Movement Disorders, a specialty of Frontiers in Neurology.

                Article
                10.3389/fneur.2011.00091
                3257846
                22275907
                6a73e614-3a10-4141-90f5-8918e905ff49
                Copyright © 2012 Louis.

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

                History
                : 12 September 2011
                : 28 December 2011
                Page count
                Figures: 0, Tables: 4, Equations: 0, References: 121, Pages: 9, Words: 8884
                Categories
                Neuroscience
                Review Article

                Neurology
                clinical,pharmacology,essential tremor,treatment
                Neurology
                clinical, pharmacology, essential tremor, treatment

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