Essential Tremor

Updated: Nov 27, 2017
  • Author: Deborah A Burke, MD; Chief Editor: Selim R Benbadis, MD  more...
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Overview

Practice Essentials

Essential tremor, the most common movement disorder, is a syndrome of unknown etiology characterized by a slowly progressive postural and/or kinetic tremor, usually affecting both upper extremities. Fundamental debate exists as to whether essential tremor is a neurodegenerative disease.

Signs and symptoms

In general, essential tremor is considered to be monosymptomatic (tremor only). Although some patients have abnormalities in gait and balance, most do not; therefore, carefully consider alternative diagnoses in the presence of gait abnormalities.

Patients with essential tremor may exhibit the following signs and symptoms:

  • Tremor begins in one upper extremity and then affects the other upper extremity; tremor rarely extends from an upper extremity to the ipsilateral lower extremity
  • Tremor may initially be intermittent, occurring during periods of emotional activation, and then becomes persistent over time
  • A mild degree of tremor asymmetry is not unusual
  • Tremor may also affect the head, voice, jaw, lips, and face
  • The tremor frequency is fixed at any point in time
  • The tremor amplitude is highly variable, worsened by emotion, hunger, fatigue, temperature extremes; the baseline amplitude gradually increases over several years; ethanol intake temporarily reduces tremor amplitude in about 50-70% of cases
  • Typically, there is a degree of voluntary control; tremor may be suppressed by performing skilled manual tasks
  • Tremor resolves when the body part relaxes as well as during sleep
  • Muscle tone and reflexes are normal; there is no bradykinesia or rigidity

See Clinical Presentation for more detail.

Diagnosis

Essential tremor is usually diagnosed based on family history and examination findings; thus, laboratory and imaging studies are usually not required. No biologic markers exist for essential tremor. Electromyography or accelerometry can be used to assess tremor frequency, rhythmicity, and amplitude but is not part of the routine evaluation.

Laboratory testing

If the patient’s family history and examination findings are not indicative of essential tremor, consider the following laboratory studies:

  • Standard electrolyte panel
  • Thyroid function tests
  • Blood urea nitrogen and creatinine levels
  • Liver function tests
  • Serum ceruloplasmin (for Wilson disease)

Imaging studies

Head computed tomography (CT) scanning and magnetic resonance imaging (MRI) findings are normal in essential tremor.

Perform MRI if the tremor has an acute onset or stepwise progression. MRI also helps to exclude structural and inflammatory lesions (including multiple sclerosis) and Wilson disease.

Single-photon emission CT (SPECT) scanning using 123I-ioflupain (DaTSCAN) may be used to support a diagnosis of parkinsonism, thereby reducing misdiagnosis of essential tremor as Parkinson disease. [1, 2, 3]

See Workup for more detail.

Management

Primidone and propranolol are the cornerstones of maintenance medical therapy for essential tremor. These medications provide good benefit, reducing tremor amplitude in approximately 50-70% of patients. [4, 5, 6]

Some patients require only intermittent tremor reduction (eg, to attend a meeting or engage in a social activity). For these patients, a cocktail or beer prior to the activity may be sufficient, or they may take propranolol (10-40 mg) approximately one half hour prior to the event.

Alcohol consumption is not an appropriate maintenance therapy for patients who seek tremor reduction throughout the day. [7]

Pharmacotherapy

The following medications are used in the management of essential tremor:

  • Nonselective beta-blockers (eg, propranolol hydrochloride)
  • Anticonvulsants (eg, primidone, topiramate)
  • Second-generation antipsychotics (eg, clozapine)
  • Antidepressants (eg, mirtazapine)

Surgery

Consider surgical intervention in patients with disabling, medically refractory upper extremity tremor. The procedures of choice are stereotactic thalamotomy and thalamic ventralis intermedius nucleus deep brain stimulation.

See Treatment and Medication for more detail.

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Background

Essential tremor is the most common movement disorder. It is a syndrome characterized by a slowly progressive postural and/or kinetic tremor, usually affecting both upper extremities. The etiology of essential tremor is not known, and fundamental debate exists as to whether essential tremor is a neurodegenerative disease. (See Etiology and Presentation.)

Inclusion and exclusion criteria

The Movement Disorders Society has proposed the following diagnostic criteria for classic essential tremor. Inclusion criteria are as follows (see Presentation and Workup):

  • Bilateral, largely symmetrical, postural (occurring with voluntary maintenance of a position against gravity) or kinetic (occurring during voluntary movement) tremor involving hands and forearms that is visible and persistent
  • Possible additional or isolated tremor in head but absence of abnormal posturing

Exclusion criteria are as follows:

  • Other abnormal neurologic signs, especially dystonia
  • The presence of known causes of enhanced physiologic tremor, including current or recent exposure to drugs that are known to cause tremor or a drug-withdrawal state
  • Historic or clinical evidence of psychogenic tremor
  • Convincing evidence of sudden onset or evidence of stepwise deterioration
  • Primary orthostatic tremor
  • Isolated voice tremor
  • Isolated position- or task-specific tremors, including occupational tremors and primary writing tremor
  • Isolated tongue or chin tremor
  • Isolated leg tremor

Association with other diseases

Essential tremor has been hypothesized to be a risk factor for the development of Parkinson disease. Some patients with Parkinson disease report a long-standing history of bilateral upper extremity postural tremor. Moreover, in a large cohort study by the Mayo Clinic, the risk of essential tremor was significantly increased in relatives of patients with Parkinson disease with younger onset and in relatives of patients with tremor-predominant Parkinson disease. (See Etiology and Presentation.) [8]

Without biologic markers for these diseases, however, determining whether long-standing postural tremor is part of a Parkinson disease syndrome or reflects the presence of both essential tremor and Parkinson disease is not possible. (See Workup.)

An association between essential tremor and dystonia has also been suggested. Some patients with focal dystonia, such as torticollis, have mild, bilateral upper extremity postural tremors. Again, however, without biologic markers for these diseases, determining whether postural tremor is part of a focal dystonia syndrome or reflects the presence of both dystonia and essential tremor is not possible.

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Etiology

The etiology of essential tremor is not known. No pathologic findings are known to be consistently associated with essential tremor. However, the following has been hypothesized:

  • Essential tremor is the result of an abnormally functioning central oscillator, which is located in the Guillain Mollaret triangle near the brainstem and involves the inferior olivary nucleus
  • The cerebellar-brainstem-thalamic-cortical circuits probably are involved
  • The pathophysiology of essential tremor is heterogeneous [9, 10]

Harmane, a heterocyclic amine (HCA), is a potent tremor-producing neurotoxin. It is often found in the human diet. Blood concentrations have been found to be elevated in patients with essential tremor as compared with controls. [11] The most likely etiology appears to be alterations in metabolism rather than increased dietary intake.

In patients with essential tremor, [18 F]fluorodeoxyglucose positron emission tomography (18F-FDG-PET) scan studies identified increased glucose consumption in the medulla. In addition, [15 O]H2 O PET scan studies demonstrated an increase in medullary regional cerebral blood flow in subjects with essential tremor (only after the administration of ethanol), and bilateral overactivity of cerebellar circuitry.

Fundamental debate exists as to whether essential tremor is a neurodegenerative disease. Data suggesting that it is neurodegenerative includes postmortem findings of pathologic abnormalities in the brainstem and cerebellum, [10] including Lewy bodies in the locus ceruleus, loss of Purkinje cells, and abnormalities of the dentate nucleus [12, 13] ; reduction in cerebellar cortical N-acetylaspartate/total creatine (NAA/tCR) [11] ; white matter changes on diffusion tensor imaging; [14] and clinical studies demonstrating an association with cognitive [15, 16] and gait changes.

Conflicting data argues against essential tremor being a neurodegenerative disease. This data includes improvement of gait abnormalities with ethanol administration, [17] lack of gray matter volume loss on voxel-based morphometry, [18] failure to confirm prominent presence of Lewy bodies in the locus ceruleus, [10] and other pathologic findings. [19]

Genetics

Essential tremor probably represents a syndrome, and multiple etiologies will likely be identified. Most or all of these causes are probably genetic.

Essential tremor is familial in at least 50-70% of cases. Transmission is autosomal dominant, with incomplete penetrance. Some cases are sporadic with unknown etiology. Twin studies suggest that genetic and environmental factors contribute to the pathogenesis. Non-Mendelian transmission in kindreds with an apparent autosomal dominant inheritance of essential tremor was demonstrated in one study. [20]

Variations in methodology (ie, assessment procedures and diagnostic criteria) account for the wide variation in findings; reported studies have found that 17% to almost 100% of cases are familial.

One study demonstrated that the frequency of having an affected relative increased from 67.7% to 96% after repeated and varied questioning followed by direct interviews of family members.

The following 3 susceptibility loci have been found:

  • 3q13 (EMT1) - Identified in 75 members of 16 Icelandic families; a Ser9Gly variant on the DRD3 gene has been associated with EMT1 [21]
  • 2p25-22 (EMT2) - Identified in 15 members of 4 generations of Americans; abnormalities found in 3 additional American families have been reported to map to this locus [22]
  • 6p23 - Identified in 2 families [23]

An association with a polymorphism in the HS1-BP3 gene has been reported, but this has not been confirmed. [20, 24]

In one family with levodopa-responsive, autosomal dominant, Lewy-body parkinsonism, a chromosome arm 4p haplotype that segregates with the disease was identified. This haplotype also occurred in individuals in the family who did not have parkinsonism but rather a postural tremor consistent with essential tremor. This suggests that in some cases, postural tremor can be an alternative phenotype of the same mutation.

LINGO1 (leucine-rich repeat and Ig-containing domain 1) variant rs9652490 has been identified as a risk factor for familial essential tremor. [25, 26, 27]

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Epidemiology

Occurrence in the United States

Assessments of the prevalence and incidence of essential tremor vary widely depending on ascertainment methodology and diagnostic criteria employed in detecting the condition. The prevalence of essential tremor is estimated to be 0.3-5.6% in the general population. A 45-year study of essential tremor in Rochester, Minn, reported an age- and sex-adjusted prevalence of 305.6 cases per 100,000 and an annual incidence of 23.7 cases per 100,000. An estimated 0.5-11.1% of affected individuals seek medical attention.

International occurrence

Using a “door-to-door” method in Mersin Province, Turkey, 2253 individuals older than 40 years were examined by neurologists; 89 essential tremor cases were identified. [28]

Race-related demographics

Race has not been extensively studied in essential tremor. One evaluation of a multiethnic group (white, African American, Hispanic) found differences in the presence or absence of head tremor and a variable tremor score among the subgroups. White subjects had a tremor score that was 5.3 points lower than that for nonwhites. Head tremors were present in 25% of whites and 29% of Hispanics and were absent in African Americans. [29]

Sex-related demographics

Essential tremor affects both sexes with equal frequency. However, head tremor may be more frequent in women, and postural hand tremor may be more severe in men. Childhood essential tremor may be more frequent in boys than in girls. [30]

Age-related demographics

The prevalence of essential tremor increases with age. Data has suggested bimodal peaks in age of onset—one in late adolescence to early adulthood and a second in older adulthood. The mean age at presentation is 35-45 years. One comparison of a population-based cohort with patients at a tertiary care center found a significant bimodal presentation only at center, with the population-based study revealing a significant peak only in older adults. This suggested that the bimodal peak may be attributable to preferential referral of young-onset essential tremor to tertiary centers. [31]

Essential tremor usually manifests by age 65 years and virtually always by age 70 years. Tremor amplitude slowly increases over time, but tremor frequency decreases with increasing age. An 8-12 Hz tremor is seen in young adults, and a 6-8 Hz tremor is seen in elderly individuals. Although essential tremor is progressive, no association has been found between age of onset and severity or disability.

Rare cases of essential tremor have been reported in newborns and infants. A strong correlation between age of onset before 20 years and family history of essential tremor was found in an environmental epidemiologic study of 195 essential tremor cases. [32]

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Prognosis

Mortality rates have been thought to be the same between patients with essential tremor and the general population. However, in a longitudinal, prospective study of patients aged 65 and older from 3 communities in central Spain, the risk of mortality in persons with essential tremor was found to be increased. [33] Further studies are needed to assess mortality rates in essential tremor.

Disability from essential tremor is common. [34] Of individuals with essential tremor, 85% report significant changes in their livelihood and socializing, and 15% report being seriously disabled by the condition.

Decreased quality of life results from loss of function and from embarrassment. In a study of hereditary essential tremor, 60% of affected individuals did not seek employment; 25% changed jobs or took early retirement; 65% did not dine out; 30% did not attend parties, shop alone, partake of a favorite hobby or sport, or use public transportation; and 20% stopped driving.

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