Treatment of patients with essential tremor

Department of Neurology, Christian-Albrechts-University Kiel, Kiel, Germany.
The Lancet Neurology (Impact Factor: 21.9). 02/2011; 10(2):148-61. DOI: 10.1016/S1474-4422(10)70322-7
Source: PubMed


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.

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    • "Additionally, automatic classification method was employed in hopes of understanding PD tremor and its response to dopaminergic medication. Early data analysis revealed RMS tremor amplitudes skewed in both bands, suggesting necessary log-transformation (see also Deuschl et al., 2011; Elble et al., 2006; Heroux et al., 2006). Data post-transformation demonstrated substantial improvement in normality (Shapiro–Wilk test) and provided the basis for analyses. "
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    ABSTRACT: In Parkinson disease, tremor is a challenging symptom to manage, partly due to inadequate characterization. The current (classic) model of tremor is characterized by a resting tremor with a single strong peak in 3.5-6.5Hz range. The presence of action tremor, including postural, isometric, and kinetic tremors, has been disputed in the literature but not comprehensively evaluated. Analysis of hand tremor in action compared to rest, and possible subgrouping of tremor trends, may improve characterization. Twenty Parkinson patients and 14 controls were recruited. Tremor amplitude was measured across 9 sequentially loaded tasks, in off and on medication states. Tremor energy was separated into 2 frequency bands (B1, 3.5-6.5Hz; B2=physiological tremor, 7.5-16.5Hz) across all activity levels. Automatic classification was used for subgroup analysis. Automatic classification yielded 3 predominant tremor trends (G1, G2, and G3). These were significantly different from each other and from controls. G1 demonstrated closest resemblance to classical Parkinsonian tremor, with highest tremor energy at rest and with overall dominance in B1 for lower loads. G2-G3 did not show tremor energy dominance in either band. Medication reduced tremor energy only for G1 in both B1 and B2. Subgrouping the loading effect on tremor is a novel and viable method of rationalizing (non-classic) action tremor in Parkinson disease. Rest and action tremors appear not to be limited to 3.5-6.5Hz and may have considerable share of physiological tremor. Finding the contribution of each frequency band to total tremor energy and their trends with load may optimize therapy options. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Clinical biomechanics (Bristol, Avon) 12/2014; 30(2). DOI:10.1016/j.clinbiomech.2014.12.012 · 1.97 Impact Factor
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    • "It is often referred to as a benign disorder but moderate and advanced stages of ET can be physically and socially disabling.1 The few medications that have been used to treat ET have demonstrated only modest efficacy.2 "
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    ABSTRACT: BACKGROUND: The GABA hypothesis in essential tremor (ET) implies a disturbance of the GABAergic system, especially involving the cerebellum. This review examines the evidence of the GABA hypothesis. METHODS: The review is based on published data about GABA dysfunction in ET, taking into account studies on cereprospinal fluid, pathology, electrophysiology, genetics, neuroimaging, experimental animal models, and human drug therapies. RESULTS: Findings from several studies support the GABA hypothesis in ET. The hypothesis follows four steps: 1) cerebellar neurodegeneration with Purkinje cell loss; 2) a decrease in GABA system activity in deep cerebellar neurons; 3) desinhibition in output deep cerebellar neurons with pacemaker activity; and 4) an increase in rhythmic activity of thalamus and thalamo-cortical circuit, contributing to the generation of tremor. Shadows are cast on this hypothesis, however, by the fact that it is based on relatively few works, controversial post-mortem findings, and negative genetic studies on the GABA system. Furthermore, GABAergic drugs efficacy is low and some GABAergic drugs do not have antitremoric efficacy. DISCUSSION: The GABA hypothesis continues to be the most robust pathophysiological hypothesis to explain ET. There are lights in all GABA hypothesis steps but a number of shadows cannot be overlooked. We need more studies to clarify the neurodegenerative nature of the disease, to confirm the decrease of GABA activity in cerebellum, and to test more therapies that enhance the GABA transmission specifically in the cerebellum area.
    07/2014; 4. DOI:10.7916/D8SF2T9C
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    • "The common pharmacological agents used for ET are summarized in Table 1. The two most effective drugs to date are primidone and propranolol.13,68 "
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    ABSTRACT: Essential tremor (ET) is the most common pathological tremor characterized by upper limb action-postural tremor (PT)/kinetic tremor (KT). There are no specific neuropathological or biochemical abnormalities in ET. The disability is consequent to amplitude of KT, which may remain mild without handicap or may become disabling. The most effective drugs for sustained tremor control are propranolol and primidone. Symptomatic drug treatment must be individualized depending on the circumstances that provoke the tremor-related disability. Broad guidelines for treatment are discussed in this review. Patients may be treated intermittently only on stressful occasions with propranolol, clonazepam, or primidone monotherapy, or an alcoholic drink. Those with persistently disabling tremor need continued treatment.
    04/2014; 6:29-39. DOI:10.4137/JCNSD.S13570
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