|Classification and external resources|
Essential tremor (ET, also referred to as benign tremor or familial tremor) is the most common movement disorder; its cause is unknown. It typically involves a tremor of the arms, hands or fingers but sometimes involving the head, vocal cords or other body parts during voluntary movements such as eating and writing. It is distinct from Parkinson's disease—and often misdiagnosed as such—although some individuals have both conditions. Essential tremor is commonly described as an action tremor (it intensifies when one tries to use the affected muscles) or postural tremor (present with sustained muscle tone) rather than a resting tremor, such as is seen in Parkinson’s, which is usually not included among its symptoms.
This type of tremor is often referred to as "kinetic tremor".
Signs and symptoms
In mild cases, ET can manifest as the inability to stop the tongue or hands from shaking, the ability to sing only in vibrato, and difficulty to do small precise tasks such as threading a needle. Even simple tasks like cutting in a straight line or using a ruler can range from difficult to impossible, depending on the severity of the condition. In disabling cases, ET can interfere with a person's activities of daily living, including feeding, dressing, and taking care of personal hygiene. Essential tremor generally presents as a rhythmic tremor (4–12 Hz) that occurs only when the affected muscle is exerting effort. Any sort of physical or mental stress will tend to make the tremor worse.
The tremor may also occur in the head (neck), jaw and voice as well as other body regions, with the general pattern being that the tremor begins in the arms and then spreads to these other regions in selected patients. Women are more likely to develop the head tremor than are men. Other types of tremor may also occur, including postural tremor of the outstretched arms, intentional tremor of the arms and rest tremor in the arms. Some patients may have unsteadiness and problems with gait and balance.
ET-related tremors do not occur during sleep, but patients sometimes complain of an especially coarse tremor upon awakening that becomes noticeably less coarse within the first few minutes of wakefulness. Tremor and disease activity/intensity can worsen in response to fatigue, strong emotions, low blood sugar, cold and heat, caffeine, lithium salts, some antidepressants, and other factors. It is typical for the tremor to worsen in "performance" situations, such as when writing a check for payment at a store or giving a presentation.
Parkinson's disease and Parkinsonism can also occur simultaneously with ET. In those cases the degree of tremor, rigidity, and functional disability does not differ from those people with idiopathic Parkinson's disease. Hand tremor predominates (as it does in Parkinson’s disease), and occurs in nearly all cases, followed by head tremor, voice tremor, neck, face, leg, tongue and trunk tremor. Most other tremors occur in association with hand tremor. Walking difficulties in essential tremor are common. About half of patients have associated dystonia, including cervical dystonia, writer's cramp, spasmodic dysphonia, and cranial dystonia, and 20% of the patients had associated parkinsonism. Olfactory dysfunction (loss of sense of smell) is common in Parkinson’s disease, and has also been reported to occur in patients with essential tremor. A number of patients with essential tremor also exhibit many of the same neuropsychiatric disturbances seen in idiopathic Parkinson's disease.
The underlying etiology of essential tremor is not clear but many cases seem to be familial. Approximately one-half of the cases are due to a genetic mutation and the pattern of inheritance is most consistent with autosomal dominant transmission. No genes have been identified yet but genetic linkage has been established with several chromosomal regions. A number of environmental factors, including toxins, are also under active investigation as they may play a role in the disease's etiology.
In terms of pathophysiology, clinical, physiological and imaging studies point to an involvement of the cerebellum and/or cerebellothalamocortical circuits. Changes in the cerebellum could also be mediated by alcoholic beverage consumption. Purkinje cells are especially susceptible to ethanol excitotoxicity. Impairment of Purkinje synapses is a component of cerebellar degradation that could underlie essential tremor. Some cases have Lewy bodies in the locus ceruleus. ET cases that progress to Parkinson's disease are less likely to have had cerebellar problems. 
Recent post mortem studies have evidenced alterations in LINGO1 (Leucine rich repeat and Ig domain containing 1) gene and GABA receptors in the cerebellum of people with essential tremor. HAPT1 mutations have also been linked to ET, as well as to Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy.
In 2012, the National Toxicology Program concluded that there is sufficient evidence of an association between blood lead exposure at levels <10 μg/dL and essential tremor in adults, and limited evidence at blood lead levels <5 μg/dL.
Usually the diagnosis is established on clinical grounds. Tremors can start at any age, from birth through advanced ages (senile tremor). Any voluntary muscle in the body may be affected, although the tremor is most commonly seen in the hands and arms and slightly less commonly in the neck (causing the patient's head to shake), tongue, and legs. A resting tremor of the hands is sometimes present. Tremor occurring in the legs might be diagnosable as orthostatic tremor.
ET occurs within multiple neurological disorders besides Parkinson's Disease. This includes migraine disorders, where co-occurrences between ET and migraines have been examined. 
When symptoms are sufficiently troublesome to warrant treatment, the first medication choices are beta blockers such as propranolol or alternately, nadolol and timolol. Atenolol and pindolol are not effective for tremor. The anti-epileptic primidone is also effective for ET.
Second-line or third-line medications can be added if the first-line medications do not control the tremor. Second-line medications are the anti-epileptics topiramate, gabapentin and levetiracetam, or benzodiazepines like alprazolam. Third-line medications are clozapine and mirtazapine.
When medications do not control the tremor or the patient does not tolerate medication, botulinum toxin, deep brain stimulation, or occupational therapy can be helpful. The electrodes for deep brain stimulation are usually placed in the "tremor center" of the brain, the ventral intermediate nucleus of the thalamus. While there are no non-invasive options available at the moment, there is an experimental treatment which involves focusing High Intensity Ultrasound beams on the affected areas of the brain which has shown promise in treating the tremors.
Although essential tremor is often mild, patients with severe tremor have difficulty performing many of their routine activities of daily living. ET is generally progressive in most cases (sometimes rapidly, sometimes very slowly), and can be disabling in severe cases.
ET is one of the most common neurological diseases, with a prevalence of approximately 4% in persons age 40 and older and considerably higher among persons in their 60s, 70s, 80s, and 90s. Aside from enhanced physiological tremor, it is the most common type of tremor and one of the most commonly observed movement disorders.
Society and culture
The actress Katharine Hepburn (1907–2003) had an essential tremor, which she inherited from her grandfather, that caused her head—and sometimes her hands—to shake. According to Dickens (1990), the tremor was noticeable by the time of her performance in the 1979 film The Corn is Green, when critics mentioned the "palsy that kept her head trembling". Hepburn's tremor worsened in the 1980s, when she was in her 70s to 80s.
Harmaline is a widely used model of essential tremor (ET) in rodents. Harmaline is thought to act primarily on neurons in the inferior olive (IO). Olivocerebellar neurons exhibit rhythmic excitatory action when harmaline is applied locally.
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