Essential tremor

ALSO KNOWN AS: Benign essential tremor; familial tremor

DEFINITION Benign essential tremor is a movement disorder most commonly characterized by shaking in the hands. It occurs in as many as 10 percent of people over the age of sixty. It may also cause shaking of the head, voice, arms, and trunk, and, less often, of the legs and feet.

Two types of tremor are common with essential tremor. Postural tremor is shaking only in certain positions, such as with arms outstretched. Kinetic or action tremor is shaking that gets worse during activities, such as eating or shaving. In some cases, essential tremor can be socially isolating. It may interfere with normal daily activities, such as writing or speaking. If so, a patient should contact his or her doctor for an evaluation.

Risk Factors

A family history of tremors is the only known risk factor for essential tremor. Although the condition may occur at any age, it is more likely to occur in people older than forty years.

Etiology and Genetics

Familial essential tremor is a condition in which multiple environmental and genetic factors play a contributing part. Approximately 50 percent of affected individuals report one or more family members who are similarly affected. The inheritance pattern may vary, but in most families an autosomal dominant mode of transmission is observed, meaning that a single copy of the mutation is sufficient to cause expression of the trait. An affected individual has a 50 percent chance of transmitting the mutation to each of his or her children. However, many cases of essential tremor result from a spontaneous new mutation, so in these instances, affected individuals will have unaffected parents. The age of onset is variable, but virtually all individuals who carry the mutation will show some expression by age seventy.

Several genes have been identified with a direct association with essential tremor, and other genes are expected to play minor roles as well. The first gene to be discovered is known variously as either DRD3 or FET1, and it is located on the long arm of chromosome 3 at position 3q13.3. This gene encodes the dopamine receptor protein D3, which is expressed in nerve cells in the brain. It responds to the neurotransmitter dopamine and triggers a signal to produce physical movement. A mutation in the FET1 gene may cause the receptor protein to react more strongly to dopamine, causing the involuntary shaking characteristic of the condition.

The second gene shown to be associated with essential tremor is HS1BP3, found on the short arm of chromosome 2 at position 2p24.1. Its protein product is the hematopoietic-specific protein 1 binding protein 3. Localized primarily in the cerebellum region of the brain, this protein helps regulate the chemical signaling involved in coordinating movements of muscles by motor neurons. A third gene on the short arm of chromosome 4, at position 4p14, is involved in only those individuals who have both Parkinson disease and essential tremor.

Researchers in 2020 reported a third gene, TUB, found to be associated with familial ET. This gene, which had already been liked to obesity, turns many other genes on and off and regulates neurotransmitter expression. Some researchers suggest more genetic links will be uncovered using long-read sequencing techniques.

Symptoms

Essential tremor is generally not serious, but its severity may vary and worsen over time. Symptoms may include a tremor that occurs when standing or moving the limbs, but not usually at rest; uncontrollable, rhythmic, up-and-down movement; shaking in hands, arms, head, voice, trunk, legs, or feet on both sides; shaking only in certain positions or during activity; and trouble with fine motor skills, such as drawing, sewing, or playing an instrument. Other symptoms may include shaking that gets worse from caffeine, stress, fatigue, or heat; hearing loss (some cases are associated with hearing loss); and problems with social, functional, or occupational abilities (more severe cases interfere with these abilities). To be considered as having essential tremor, an individual’s tremors must not be related to other health conditions.

Screening and Diagnosis

The doctor will ask about a patient’s symptoms and his or her medical and family history. The doctor will also do a physical exam, paying particular attention to the patient’s central nervous system. At this time, there are no special tests to diagnose essential tremor. However, patients may have blood, urine, or other tests, such as a magnetic resonance imaging (MRI) scan, to rule out other causes, like Parkinson disease, elevated thyroid hormone, low blood sugar, stroke, and medications.

Treatment and Therapy

Most people with essential tremor do not require treatment. Mild tremors may be relieved or even eliminated by simple measures, including staying well rested, avoiding caffeine, avoiding stimulants often found in over-the-counter medications such as cold remedies, and avoiding temperature extremes.

Individuals should talk to their doctors about any medications that may be contributing to their symptoms. If a patient’s symptoms are troubling, treatment options that may be helpful include beta blockers, such as propranolol (a blood pressure medication); antiseizure medications, such as primidone (Mysoline), gabapentin (Neurontin), or topiramate (Topamax); and sedatives (benzodiazepines).

Botulinum injections may be used in rare situations. In rare cases where tremors are very disabling and medications do not help, surgery may be an option. Two approaches are common: deep brain stimulation (DBS) and thalamotomy. DBS transmits painless electrical pulses to the brain, interrupting faulty signals. Thalamotomy destroys a tiny part of the brain generating the tremors; it is less commonly performed than DBS.

In 2024, researchers announced a new treatment for essential tremors that successfully treated patients. With HiFU (high intensity focused ultrasound), a small incision is made deep inside the brain, targeting the area that regulates movement. UC Health in Colorado began treating patients with the procedure in 2020 but were halted because of the COVID-19 global pandemic. They began treating patients with HiFU again in 2023 when twenty-three patients successfully underwent the treatment, which is performed while the patient is awake and in an MRI scanner.

Prevention and Outcomes

There is no known way to prevent essential tremor.

Bibliography

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