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.
"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. "
"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 "
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
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