Mirtazapine treats resting tremor, essential tremor, and levodopa-induced dyskinesias.
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Adrenergic alpha-Antagonists↗
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Electrophysiologic transition from physiologic tremor to essential tremor.
We electrophysiologically examined the transition from physiologic tremor to essential tremor in people at risk for familial essential tremor. Two healthy people from different families with hereditary essential tremor were studied on multiple occasions. A 23-year-old man was studied in 1995, 1997, and 2004, and a 44-year-old woman was studied in 1993, 1995, 1997, and 2003. Hand acceleration and forearm electromyographic readings were measured with and without 300-g loading to determine the characteristic frequency-invariant motor unit entrainment of essential tremor. Clinically and electrophysiologically, the man and woman had normal tremor until the last examination, when both exhibited a fine tremulousness in the outstretched hands and frequency-invariant motor unit entrainment at 7.5 and 6.5 Hz, respectively. At no time did either patient exhibit a prominent 8-12 Hz component of physiologic tremor. Essential tremor in young adults may begin at frequencies less than 8-12 Hz, and this electrophysiologic abnormality is detectable when clinical examinations reveal only questionably abnormal tremor. More young adults at risk for essential tremor must be studied to determine whether initial frequencies less than 8 Hz are the rule or the exception. Nevertheless, the data from our 2 patients demonstrate that a prominent 8-12 Hz component of physiologic tremor does not always precede the development of essential tremor; therefore, the origins of essential tremor and the 8-12 Hz component of physiologic tremor may be different.
Adult↗
Benefits and risks of pharmacological treatments for essential tremor.
Essential tremor can cause significant functional disability in some patients. The arms are the most common body part affected and cause the most functional disability. The treatment of essential tremor includes medications, surgical options and other forms of therapy. Presently there is no cure for essential tremor nor are there any medications that can slow the progression of tremor. Treatment for essential tremor is recommended if the tremor causes functional disability. If the tremor is disabling only during periods of stress and anxiety, propranolol and benzodiazepines can be used during those periods when the tremor causes functional disability. The currently available medications can improve tremor in approximately 50% of the patients. If the tremor is disabling, treatment should be initiated with either primidone or propranolol. If either primidone or propranolol do not provide adequate control of the tremor, then the medications can be used in combination. If patients experience adverse effects with propranolol, occasionally other beta-adrenoceptor antagonists (such as atenolol or metoprolol) can be used. If primidone and propranolol do not provide adequate control of tremor, occasionally the use of benzodiazepines (such as clonazepam) can provide benefit. Other medications that may be helpful include gabapentin or topiramate. If a patient has disabling head or voice tremor, botulinum toxin injections into the muscles may provide relief from the tremor. Botulinum toxin in the hand muscles for hand tremor can result in bothersome hand weakness and is not widely used. There are other medications that have been tried in essential tremor and have questionable efficacy. These drugs include carbonic anhydrase inhibitors (e.g. methazolamide), phenobarbital, calcium channel antagonists (e.g. nimodipine), isoniazid, clonidine, clozapine and mirtazapine. If the patient still has disabling tremor after medication trials, surgical options are usually considered. Surgical options include thalamotomy and deep brain stimulation of the thalamus. These surgical options provide adequate tremor control in approximately 90% of the patients. Surgical morbidity and mortality for these procedures is low. Deep brain stimulation and thalamotomy have been shown to have comparable efficacy but fewer complications have been reported with deep brain stimulation. In patients undergoing bilateral procedures deep brain stimulation of the thalamus is the procedure of choice to avoid adverse effects seen with bilateral ablative procedures. The use of medication and/or surgery can provide adequate tremor control in the majority of the patients.
Adrenergic Agonists↗
The role of aging in the clinical expression of essential tremor.
Essential tremor is the most common form of abnormal tremor. It is a monosymptomatic disorder characterized by action tremor but no other sign of motor dysfunction. More than half of all cases are inherited through a Mendelian dominant gene. Mild essential tremor is probably the cause of tremulousness that is frequently attributed to aging. The prevalence of essential tremor increases with age, and aging appears to have an independent effect on the clinical characteristics of essential tremor. Autopsies have revealed no discernible pathology. Essential tremor probably emerges from subtle pathologic transformation of a physiologic neuronal oscillator, possibly the inferior olive. A more complete characterization of the effects of aging on motor pathways may be necessary to fully understand the natural history and pathogenesis of this disorder.
Adolescent↗
Clinical features, assessment and treatment of essential tremor.
Essential tremor is the most common of the movement disorders, being 20 times more common than Parkinson's Disease. It is characterised by postural and kinetic tremor which maximally affects the hands. It can be assessed by physiological techniques, subjective clinical methods, objective clinical methods and handicap/disability scales. Accelerometry, spirography and handwriting assessment, volumetry and handicap/disability questionnaires are commonly used methods. Primidone and propranolol are the first-line drugs. Several second-line drugs have been identified. Surgical techniques include lesioning or stimulation of the ventral lateral thalamus. Alcohol and botulinum toxin A are found to reduce tremor amplitude as well.
Essential Tremor↗
Deep brain stimulation and essential tremor.
Essential tremor (ET) is one of the most common movement disorders and can cause significant functional disability in some patients. Although medications can improve tremor in some patients, approximately 50% of patients have medication-resistant symptoms. In patients with ET who experience marked disability due to the tremor, surgical therapy, primarily deep brain stimulation (DBS) of the ventral intermediate (Vim) nucleus of the thalamus, is a viable treatment option. Multiple studies of DBS of the thalamus have shown that it is efficacious in the treatment of ET hand tremor, often with secondary improvement in voice and head tremor. Long-term studies have reported that a majority of patients continue to experience improvement in tremor. Adverse effects related to stimulation are usually mild and can be managed with changes in stimulation parameters. Long-term hardware complications include equipment malfunction, skin erosion, and battery replacements, which require additional surgery. Deep brain stimulation of the thalamus is a safe and efficacious procedure and should be considered in patients with ET who experience medication-resistant disabling tremor.
Brain Mapping↗
Management of essential tremor.
Essential tremor (ET) is the most prevalent tremor syndrome. It commonly affects the hands, head, voice, and other body parts. Appropriate management begins with correct diagnosis. Primidone and propranolol are the first-line medications for the treatment for ET, but several other medications may also provide benefit. In patients with medically refractory tremor, alternative therapies, including surgery or injections of botulinum toxin, may be considered.
Adrenergic alpha-Antagonists↗
HS1-BP3 gene variant is common in familial essential tremor.
Essential tremor (ET) is a movement disorder characterized by a postural or kinetic tremor of the hands, head, or voice. It is typically a familial condition and affects 1% to 4% of the general population. The trait is genetically linked to chromosome 2p in some families. A variant (828C-->G) in exon 7 of the hematopoietic-specific protein 1 binding protein 3 gene (HS1-BP3) on chromosome 2p recently has been found to segregate with ET in 2 families. To determine the frequency of this variant in a larger series, we studied patients with ET, Parkinson disease (PD), and controls without tremor. Affected singletons representing 73 families from the United States with dominantly inherited ET, 35 individuals with PD, and 304 healthy controls older than age 60 were tested for the 828C-->G variant in exon 7 of the HS1-BP3 gene by a BseYI restriction enzyme digest of the polymerase chain reaction product. Heterozygous carriers of the mutant allele were identified in 12 individuals with ET (16.4%) and in 1 individual with PD and postural tremor (3%). All of the healthy controls (608 chromosomes) were homozygous for the wild-type allele. The 828C-->G genetic variant in the HS1-BP3 gene occurs relatively frequently in subjects with ET. The variant may also be found in some individuals with PD and postural tremor. The HS1-BP3 gene plays a putative role in regulating catecholamine and serotonin metabolism, but the functional consequences of the amino acid substitution (A265G) caused by this genetic variant is unknown.
Aged↗
Posturographic analysis of balance control in patients with essential tremor.
Essential tremor (ET) is a common movement disorder causing an important functional disability. ET is generally regarded as a monosymptomatic disorder, but additional signs may be present. We analyzed postural sway in 19 patients with classic ET and in 19 sex- and age-matched normal controls (NC) to uncover possible abnormalities of balance control. Static posturography was performed with eyes open (EO) and closed during quiet stance and during performance of mental calculation or motor sequence of thumb opposition to the other fingers. No significant differences of center of foot pressure (COP) parameters were observed between patients and controls during quiet standing. Visual deprivation induced a similar worsening of postural sway in both groups. Concomitant performance of a cognitive or motor task did not affect COP area, whereas COP path was significantly modified by the cognitive task in both groups. In all EO conditions, the COP path was significantly lower in NC than in ET, but such offset was related only to the group of ET patients with head tremor. This study demonstrates that balance control is only minimally affected in ET, although patients with head involvement and longer disease duration tend to present a reduced postural stability. The "dual-task effect" is less important in ET than in Parkinson's disease patients.
Adult↗
Essential tremor.
Essential tremor (ET) is among the most common neurologic disorders. The traditional view of this disorder as a benign, monosymptomatic, familial condition is being replaced by a more complex view of ET as perhaps a family of diseases with etiologic, clinical, and pathologic heterogeneity. This article discusses the major clinical features of ET and approaches to its diagnosis and treatment.
Central Nervous System Agents↗
[How I treat ... essential tremor].
Essential tremor is the most prevalent movement disorder. This condition is often considered as benign but it can be the cause of considerable social, professional, and psychological handicap. It affects people of all ages but its prevalence increases with age (up to 5% of patients 65 or older). After discussing clinical aspects of this disorder, we review the current medical and surgical therapeutic options. Surgery may bring up spectacular improvement.
Diagnosis, Differential↗
Epidemiology and genetics of essential tremor.
Essential tremor (ET) is probably the most common movement disorder and is a common cause of social, physical, and psychological handicaps. Its etiology and pathogenesis are unknown. Phenomenologically, ET overlaps and is associated with other disorders of movement, such as parkinsonism and dystonia. There is large variation in the stated prevalence of ET as well as limited availability of epidemiologic studies. Prevalence variations reflect differences in the definition of ET and the methodologies of investigation. The familial and sporadic forms of ET are generally assumed to be similar. The familial form appears to have a narrow phenotype. Wide variation in the reported percentage of patients with positive family history reflects ascertainment and classification differences. Linkage of ET to two different chromosome locations has been reported.
Adult↗
Essential tremor.
Essential tremor (ET) is one of the most common neurological diseases; although it is a disease about which we are only beginning to develop an understanding. Effective treatment options for the disorder are severely limited. The traditional view of ET as a benign, familial, monosymptomatic disorder is being replaced by one of ET as a disease or family of diseases with aetiological, clinical, and pathological heterogeneity. Recent identification of putative environmental toxins linked to ET provide hope for disease prevention through a reduction in exposure to risk factors. Pathological and genetic studies will yield new insights into disease pathogenesis and mechanisms, which may result in the development of more effective symptomatic therapies developed with an understanding of the disease biology. These insights also have the potential to form the basis for neuroprotective therapies.
Essential Tremor↗
Pharmacologic treatment of essential tremor.
Essential tremor (ET) is a common movement disorder that often causes functional disability, potentially leading to physical and emotional difficulties. The paucity of data available regarding the underlying pathophysiologic mechanism of ET hinders the development of innovative approaches to pharmacotherapeutic treatments. Options for drug therapy include the use of primidone, beta-adrenergic blockers, such as propranolol, alcohol, and other drugs, such as benzodiazepines, gabapentin, carbonic anhydrase inhibitors, clozapine, flunarizine, clonidine, and the methylxanthine derivative theophylline. Chemodenervation with botulinum toxin type A may be a therapeutic option for selected patients with ET. Each drug is classified as to the quality of evidence for efficacy and the suggested strength of therapeutic recommendation. In general clinical practice, primidone and propranolol have proven efficacy in ET.
Aged↗
Comparison of clinical vs. electrophysiological methods of diagnosing of essential tremor.
Essential tremor (ET) may be differentiated from normal or enhanced physiological tremor based on a clinical examination or electrophysiological tests such as quantitative computerized tremor analysis. There have been few head to head comparisons of the two methods. Our objective was to estimate diagnostic agreement between these two methods. Cases and controls underwent a clinical evaluation (interview and videotaped examination) and an electrophysiological evaluation (quantitative computerized tremor analysis using accelerometry and electromyography) on the same day, and diagnoses were independently assigned using clinical vs. electrophysiological criteria. Agreement between diagnoses was assessed with a concordance rate and kappa statistic (kappa).Thirty-two (59.3%) of 54 subjects were diagnosed clinically as ET (possible, probable, or definite), compared with 35 (64.8%) of 54 based on tremor analysis. The concordance rate between the two methods of diagnosis was 94.4% (51 of 54). Kappa was 0.88, indicating a level of agreement between diagnoses that was in the "near perfect" range. All of the subjects who received electrophysiological diagnoses of definite ET also received clinical diagnoses of ET. Conversely, all of the subjects who received clinical diagnoses of definite ET also received electrophysiological diagnoses of ET. The agreement between the clinical and electrophysiological diagnosis of ET was substantial, suggesting that study protocols that were to utilize either technique would arrive at similar diagnostic conclusions. In addition, physiological testing can quantify potentially valuable subclinical measurements as well as detect possible additional cases of ET not diagnosed as such during clinical assessments.
Adult↗
Cognitive functioning in individuals with "benign" essential tremor.
Essential tremor (ET) is the most common type of movement disorder, although its etiology and neurophysiological substrates remain unclear. While thought to be a benign condition, it has yet to be studied from a neuropsychological perspective. We examined the neurocognitive functioning of 13 nondemented subjects with severe ET, including aspects of memory, cognitive flexibility, and attention. Results revealed that 12/13 subjects demonstrated impairment on 1 or more cognitive measures in comparison with published normative data. The pattern of findings was suggestive of relative dysfunction of frontal-mediated processes not unlike that seen in Parkinson's disease. These deficits were found in subjects irrespective of the presence of cognitive complaints, depression, or the existence of other potential neurocognitive risk factors. These findings suggest that mild cognitive deficits are not uncommon in association with severe ET and may be related to subcortical systems.
Adult↗
Visuomotor performance in patients with essential tremor.
Essential tremor (ET) is the most prevalent extrapyramidal disorder, yet its diagnosis is still controversial. This article introduces new findings that pertain to this diagnostic problem. Twenty-three patients with ET were studied. Patients with parkinsonism, cerebellar signs, severe head injury, or those under neuroleptic medication were excluded. Twenty-five normal subjects served as control subjects. Visuomotor tests involving tracking and tracing along three different paths with both the right and left hands, were used. Performance was assessed by measuring test duration, directional error, the proportion of the cumulative test time during which directional error exceeded half the maximal possible level (PT50%), the mean distance from the model path, the velocity of the hand movement, and the number of tracking interruptions. In 15 of 23 patients performance was the same as in the control subjects. These patients were defined as having a "simple condition" of ET (ETs). Considerable visuomotor impairment was found in eight patients who were regarded as having a "complex condition" of ET (ETc). Patients with ETc had significantly lower tracking speed, more tracking interruptions, longer test duration, greater directional error, greater PT50%, and greater distance from path than patients with ETs or control subjects. Most patients with ET appear to have normal visuomotor capabilities (ETs) but some display significant visuomotor disturbances (ETc). Considering the presence of similar impairments in patients with early Parkinson's disease and the increased prevalence of parkinsonism in patients with ET, it is possible that preclinical parkinsonism exists in patients with ETc. Further follow up of patients with ETc is necessary to verify this possibility.
Disease Progression↗
[Molecular genetic analysis of essential tremor].
Essential tremor (ET) is the most common extrapyramidal disorder of the central nervous system with autosomal dominant transmission in the majority of cases and age-dependent penetrance of the mutant gene. In a number of cases, it shares some phenotypic features with autosomal dominant idiopathic torsion dystonia (locus DYT1 on chromosome 9q32-34) and is genetically heterogeneous: distinct variants of ET were mapped to chromosomes 3q13 (ETM1) and 2p22-25 (ETM2). We performed studies of candidate loci in a group of Slavonic (11 patients) and Tajik (19 patients) families with ET. Mutational analysis of the DYT gene in probands did not reveal the major deletion 946-948delGAG characteristic of idiopathic torsion dystonia, which allows one to genetically distinguish the studied hereditary forms of ET and torsion dystonia. Based on analysis of genetic linkage in informative Tajik pedigrees with ET, linkage to locus ETM1 on chromosome 3q13 was established in four families. Maximum pairwise Lod score was 2.46 at recombination fraction of theta = 0.00; maximum combined multipoint Lod score was 3.35 for marker D3S3720 and a common "mutant" haplotype for markers D3S3620, D3S3576, and D3S3720 allowed us to locate a mutant gene in a relatively narrow chromosome region spanning 2 cM. In one informative pedigree with ET, both candidate loci ETM1 and ETM2 were definitely excluded on the basis of negative Lod scores obtained by linkage estimations, which testifies to the existence of another distinct gene for autosomal dominant ET.
Carrier Proteins↗