INTRODUCTION —
Essential tremor (ET) is the most common cause of action tremor in adults. It classically involves the hands and is brought out by arm movement and sustained antigravity postures, affecting common daily activities such as writing, drinking from a glass, and handling eating utensils. ET is slowly progressive and can involve the head, voice, and rarely the legs, in addition to the upper limbs.
ET often runs in families and can be referred to as "familial tremor" when there is a family history. The term "benign essential tremor" was used in the past to distinguish ET from Parkinson disease (PD). However, the use of "benign" as a modifier for ET is best omitted, since the tremor can be severe and disabling.
This topic will cover the epidemiology, pathogenesis, clinical features, and diagnostic evaluation of ET. The treatment and prognosis of ET are discussed separately. (See "Essential tremor: Treatment and prognosis" and "Surgical treatment of essential tremor".)
EPIDEMIOLOGY —
ET is the most common cause of action tremor, with an estimated prevalence worldwide of 1 percent overall and approximately 5 percent in adults over the age of 60 years [1-3]. The incidence of ET increases with age, although childhood and early adulthood presentations do occur, especially when ET is familial [4].
The prevalence of ET is similar in males and females, although some studies report a slight male predominance [3].
PATHOGENESIS AND GENETICS —
The pathogenesis of ET is largely unexplained, and phenotypic and genetic heterogeneity suggest that ET may represent a syndrome of related disorders rather than a single disease [5,6].
There appears to be a strong genetic component. A family history of tremor is present in 30 to 70 percent of patients with ET. The proportion is as high as 80 percent among those with onset at or before the age of 40 years [7,8]. Evidence from family and linkage studies suggests an autosomal dominant inheritance pattern with reduced penetrance [7,9-13].
First-degree relatives of patients with ET have an increased risk of developing the disorder, particularly when the proband develops ET at an early age [14]. The lack of 100 percent concordance among monozygotic twins suggests that environmental factors are also involved in the pathogenesis [15].
A number of risk variants have been identified in genome-wide association studies [16]. Putative risk genes requiring further validation include leucine-rich repeat and immunoglobulin domain-containing protein 1 (LINGO1), solute carrier family 1 member 2 (SLC1A2), serine/threonine kinase 32B (STK32B), PPARG coactivator 1 alpha (PPARGC1A), and catenin alpha 3 (CTNNA3) [17-21]. An apparently pathogenic rare variant in the fused in sarcoma (FUS) gene, distinct from those that cause a form of familial amyotrophic lateral sclerosis, was reported in one large family with hereditary ET [22]. Repeat guanine-guanine-cytosine (GGC) expansion in the notch 2 N-terminal like C (NOTCH2NLC) gene has been associated with ET in a small subset of Chinese families with ET [23]. (See "Familial amyotrophic lateral sclerosis", section on 'ALS6 (FUS gene)'.)
The neuropathologic basis of ET remains poorly defined and controversial, but most evidence points to dysfunction of the cerebellothalamic pathways [24-33]. When examined carefully, patients with ET will often display gait ataxia, subtle dysmetria, and dysdiadochokinesia characteristic of cerebellar disorders [34]. A systematic review of 51 neuroimaging studies in patients with ET noted that most studies identified functional and structural brain abnormalities in various parts of the cerebellum, but these reports lacked consistent findings that would support a conclusive topography of neurodegeneration or correlation with clinical symptoms of ET [35]. Others suggest that ET is a network disorder that includes the cerebellum as the hub, functionally connected to thalamus, motor cortex, precuneus, inferior parietal lobe, and insula [36].
CLINICAL FEATURES
Tremor characteristics — ET is an action tremor that classically affects the hands and arms, is typically bilateral, and may be slightly asymmetric. It can also affect the head, voice, and less commonly the face or trunk.
The tremor of ET is notable with posture holding (ie, arms are held in a fixed posture against gravity) and with targeted or goal-directed limb movements (eg, using utensils, drinking from a glass, writing). Although ET is typically absent when the affected body part is at rest and supported against gravity, ET may overflow into a limb or other body part when the person is not completely relaxed, giving the appearance of a rest tremor. ET also becomes immediately apparent when arms are held outstretched, in contrast to the latency associated with action tremor in a patient with Parkinson disease (PD). (See 'Parkinson disease' below.)
The frequency of ET is typically moderate to high (6 to 12 Hz) but can vary from a low-amplitude, high-frequency postural tremor of the hands to a large-amplitude coarse tremor that is activated by particular movements [37,38].
Tremor of the head due to ET may be vertical ("yes-yes") or horizontal ("no-no") and is usually associated with tremor of the hand or voice [39]. According to diagnostic criteria, isolated head or voice tremor is not consistent with ET [40]. Isolated head tremor often suggests the diagnosis of cervical dystonia with dystonic head tremor, and isolated tremor of the voice is usually due to spasmodic dysphonia. (See 'Dystonic head tremor' below and 'Laryngeal dystonia' below.)
Lower limb or jaw tremor are highly unusual for ET and often suggest PD. (See 'Parkinson disease' below.)
Exacerbating and relieving factors — ET can be exacerbated by anxiety, stress, excitement, or other forms of adrenergic stimulation. In contrast to physiologic tremor, ET is not usually exacerbated by caffeine. Patients may report the diagnostic clue that their tremor is relieved or dampened by alcohol.
"Soft" neurologic signs — By definition, tremor should be the only neurologic manifestation of ET. However, in some cases, difficulty with tandem gait, mild cognitive impairment, and slight overflow of the tremor into a resting posture may be present. Proposed, though controversial, terminology used to describe ET with such soft neurologic signs is so-called "ET plus" [40,41]. (See 'Clinical criteria' below.)
Preliminary studies suggest that very mild cognitive deficits with reduced performance on tests of memory and frontal executive function may be more common in patients with ET than age-matched controls [42-45], and that ET may be associated with an increased risk of dementia [46,47].
Natural history — ET tends to progress slowly over time. Symptoms of ET are often present for years to decades before patients seek medical attention.
There may sometimes appear to be a stepwise worsening of tremor, perhaps due to other exacerbating factors such as anxiety, medical illness, or the addition of new medications. Spread to previously uninvolved body parts may also occur.
Disability from the tremor is significant when using tools or eating utensils, holding drinks, writing, and signing documents. (See "Essential tremor: Treatment and prognosis", section on 'Prognosis'.)
DIFFERENTIAL DIAGNOSIS —
Although ET may be the most common isolated action tremor syndrome (table 1), there is a broad differential diagnosis for kinetic and postural tremors. The main considerations in the differential diagnosis of ET are enhanced physiologic tremor, parkinsonian tremor, and dystonic tremor (algorithm 1).
Enhanced physiologic tremor — Enhanced physiologic tremor is a common cause of action tremor and can mimic mild ET.
Healthy individuals may have a symmetrical, fine low-amplitude, high-frequency (8 to 12 Hz) physiologic action tremor in the upper limbs. Physiologic tremor is usually not visible under ordinary circumstances, although some people have a natural tendency to demonstrate mild, nondisabling physiologic tremor.
Factors that increase sympathetic drive can enhance physiologic tremor to the point of detection. Examples include stress, anxiety, or excitement. Muscle fatigue, fever, hypoglycemia, alcohol or opioid withdrawal, and a variety of medications, drugs, and substances can also enhance physiologic tremor (table 2). (See "Overview of tremor", section on 'Physiologic tremor'.)
Enhanced physiologic tremor can fluctuate and resolve with removal of the precipitating factor, while ET is chronic and tends to be non-remitting.
Parkinson disease — Differentiating between a parkinsonian tremor and ET is the most common scenario facing clinicians and is a primary concern of patients presenting with tremor.
The classic tremor of Parkinson disease (PD) is a rest tremor that typically begins unilaterally (table 3). However, it is important to note that tremor of PD is not only a rest tremor, and an action tremor may be one of the earliest manifestations. The presence of a unilateral action tremor associated with bradykinesia, hypokinesia, or rigidity is still consistent with a diagnosis of PD.
Patients with PD may present with a rapid postural or action tremor indistinguishable from ET before they display other signs of PD [48]. In this scenario, unilateral action tremor may represent PD, since ET often develops bilaterally. In addition, patients with PD may develop a tremor similar in frequency and amplitude to their rest tremor that emerges after a latency during posture-holding (the so-called "re-emergent tremor"). By contrast, ET is apparent immediately with posture-holding and action.
Conversely, patients with severe ET may have a rest component to their tremor in the arms or hands. Older adult patients with ET may have subtle bradykinesia or cogwheel phenomenon, which needs to be followed as it may signify the emergence of PD.
Involvement of certain body parts can also be helpful in distinguishing PD and ET. While a tremor of the head and neck is more likely to be a symptom of ET, tremor of the jaw or lips is more commonly due to PD. A rest tremor involving the foot or legs almost always suggests a parkinsonian tremor and excludes ET.
Additional characteristics of tremor in patients with PD are reviewed separately. (See "Clinical manifestations of Parkinson disease", section on 'Tremor'.)
Dystonic head tremor — An isolated head tremor without action tremor in the upper limbs or signs of cerebellar dysfunction suggests the alternate diagnosis of dystonic head tremor due to cervical dystonia (previously called spasmodic torticollis).
Cervical dystonia is the most common adult-onset focal dystonia and typically leads to head rotation (torticollis), tilt (laterocollis), flexion, or extension. The older term "spasmodic" referred to the tremor of the head that is common in cervical dystonia. Cervical dystonia may also present primarily as an isolated head tremor, with minimal pain, stiffness, or deviation of the head.
Dystonic head tremor tends to be more irregular and jerk-like than ET-related head tremor and increases with changes in head position, most often when rotating the head away from the side of torticollis (directional preponderance).
To help distinguish head tremor in ET from dystonic head tremor, patients should be examined in the supine position with the head fully supported and relaxed. Essential head tremor tends to resolve in the supine position, whereas dystonic head tremor generally persists [49]. Postural changes of the head, neck, and shoulders in repose and passive range of motion of the neck in the horizontal and vertical planes should also be examined for evidence of an underlying dystonia. (See "Cervical dystonia: Etiology, clinical features, and diagnosis", section on 'Clinical features'.)
Laryngeal dystonia — Voice tremor may be a manifestation of ET but rarely occurs in isolation; when it does, it is important to differentiate it from laryngeal dystonia (formerly called spasmodic dysphonia), a focal dystonia. Essential voice tremor is best identified by asking the patient to hold a steady note such as "ahhhh" or "eeeee." With ET, the vocal cords oscillate, leading to a tremulous, quivering, or shaky voice. With laryngeal dystonia, the voice may break, appear strangulated and hoarse with adductor spasm, or alternatively sound breathy or weak with abductor spasm. (See "Etiology, clinical features, and diagnostic evaluation of dystonia", section on 'Laryngeal dystonia'.)
Cerebellar outflow tremor — Cerebellar outflow tremor (also known as Holmes or rubral tremor) should be considered when the tremor is most notable with precise and goal-directed hand movements such as finger-nose testing or reaching for a cup or utensil. Intention and targeting are affected by errors in precision, amplitude, and gross over- and under-corrections. These tremors can be dramatic, coarse large-amplitude, and involve proximal muscles, and they are often very disabling and medically refractory. When the arms are suspended and flexed at the elbows, a characteristic coarse flapping called "wing-beating" may appear.
On examination, additional signs that suggest a brainstem and/or cerebellar localization rather than ET are usually apparent, such as side-to-side bobbing of the head (known as titubation), gait ataxia, cerebellar dysarthria, dysmetria, and dysdiadochokinesia. These point to a typical brainstem and/or cerebellar localization. Cerebellar outflow tremor is usually caused by a pathologic process such as a stroke, hemorrhage, or a demyelinating lesion affecting dentatorubrothalamic pathways surrounding the red nucleus. (See "Overview of cerebellar ataxia in adults".)
Other action tremors — Other less common causes of action tremor that may occasionally overlap in some ways with ET, including task-specific tremor such as writing tremor and orthostatic tremor, a form of postural tremor, are reviewed separately. (See "Overview of tremor", section on 'Action tremors'.)
DIAGNOSIS —
The diagnosis of ET is based primarily on clinical features [50]. Imaging, blood work, and other evaluations are not necessary to make a diagnosis, but they can be used to exclude other potential causes of tremor.
Clinical criteria — In practice, ET is diagnosed by the following (algorithm 1):
●Bilateral upper limb action tremor, with or without head or voice tremor
●Normal neurologic examination aside from tremor
●Exclusion of other causes (eg, medications (table 2), hyperthyroidism, or metabolic abnormality)
Formal diagnostic criteria from the International Parkinson and Movement Disorder Society (IPMDS) task force define ET by the following four features [40]:
●Isolated tremor consisting of bilateral upper limb action (kinetic and postural) tremor, without other motor abnormalities
●At least three years in duration
●With or without tremor in other locations (eg, head, voice, or lower limbs)
●Absence of other neurologic signs, such as dystonia, ataxia, or parkinsonism
The IPMDS consensus statement also defines the diagnostic category of ET plus, which should be used to label patients with "soft" neurologic signs that are of uncertain significance and relationship to the tremor, such as questionable dystonic posturing, rest component of tremor, and memory impairment [40]. (See '"Soft" neurologic signs' above.)
Previous criteria for ET recognized family history of ET and beneficial response to alcohol as secondary criteria [51]; while these are common in patients with ET, the IPMDS felt that they were not consistent enough to include in the definition [40].
History and neurologic examination — The history should include information on age of onset of tremor, degree of progression over time, involved body parts, activities that are most affected by the tremor, relieving factors such as alcohol, and family history of ET in grandparents, parents, or siblings. In addition, details about embarrassment, level of social disability, and specific ways in which the tremor affects patient function are important to elicit and document.
Exacerbating factors such as exercise, fatigue, or stress should be elicited. Interestingly, caffeine usually does not aggravate ET, although it does aggravate physiologic tremor. A complete list of medications should be reviewed to exclude the possibility that a medication is exacerbating a physiologic tremor. (See 'Enhanced physiologic tremor' above.)
A detailed neurologic examination aims to identify specific features of the tremor, including its frequency (estimated by visual inspection), amplitude, body distribution, and activating conditions (ie, whether the tremor appears at rest, with antigravity posture, or voluntary goal-directed activity), and to identify other neurologic findings if present, in particular signs of parkinsonism (eg, rigidity, bradykinesia, postural instability) [52]. Handwriting and drawing samples (eg, tracing a spiral) are helpful; features such as micrographia may also point to parkinsonism. In patients with relatively isolated head tremor, the head should be examined in the supine position, fully supported. (See 'Dystonic head tremor' above.)
Laboratories — Routine laboratory tests should be performed to exclude common treatable causes of enhanced physiologic tremor, including electrolytes (particularly serum calcium) and liver and thyroid function tests. Diagnostic studies to exclude Wilson disease should be considered in anyone under age 40 who has unexplained tremor or other involuntary movements. (See "Wilson disease: Clinical manifestations, diagnosis, and natural history".)
Indications for brain imaging — Structural brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) is generally not required in patients with typical clinical features of ET (ie, long duration of bilateral symptoms, absence of other neurologic findings). Neuroimaging should be pursued when there are focal neurologic examination findings or sudden onset of symptoms that suggest a possible structural cause for tremor, such as stroke, demyelinating disease, or mass lesion.
Role of dopamine transporter imaging — Striatal dopamine transporter imaging using ioflupane I-123 single-photon emission computed tomography (SPECT; DaTscan) is normal in patients with ET and can reliably distinguish ET from disorders associated with nigrostriatal degeneration, namely Parkinson disease (PD) and other parkinsonian syndromes (ie, dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration). (See "Diagnosis and differential diagnosis of Parkinson disease", section on 'DaTscan'.)
While DaTscan is not needed to diagnose ET in most patients, DaTscan may be helpful for the following scenarios:
●Patients for whom the diagnosis of ET versus PD is unclear after serial clinical evaluations
●Patients with longstanding ET who later develop equivocal signs of PD and fail to respond to levodopa
●Patients with ET who are possible candidates for deep brain stimulation but have emerging signs of parkinsonism
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Essential tremor".)
PATIENT PERSPECTIVE TOPICS —
Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: Essential tremor with onset in childhood" and "Patient perspective: An artist with essential tremor".)
SUMMARY AND RECOMMENDATIONS
●Epidemiology – Essential tremor (ET) is the most common cause of action tremor (table 1), with an estimated prevalence worldwide of 1 percent overall and approximately 5 percent in adults over the age of 60 years. (See 'Epidemiology' above.)
●Pathogenesis – Although the pathogenesis of ET is largely unexplained, there is a strong genetic component. A family history is present in 30 to 70 percent of patients with the disorder. (See 'Pathogenesis and genetics' above.)
●Clinical features – ET is an action tremor that classically affects the hands and arms, is virtually always bilateral, and may be asymmetric. It can also affect the head/neck, voice, and, less commonly, the face or trunk. Tremor of the leg or jaw tends to exclude a diagnosis of ET. (See 'Tremor characteristics' above.)
ET is often aggravated by anxiety or other adrenergic stimulation and may be relieved by small amounts of alcohol. (See 'Exacerbating and relieving factors' above.)
ET was historically referred to as "benign" due to its stable course and very slow progression, but it affects common daily activities such as writing, drinking from a glass, and handling eating utensils and can be very disabling. (See 'Natural history' above.)
●Differential diagnosis – The main considerations in the differential diagnosis of ET are enhanced physiologic tremor, Parkinson disease (PD) and other parkinsonian syndromes (table 3), and dystonic head tremor. Spasmodic dysphonia should also be considered in patients with isolated vocal tremor. (See 'Differential diagnosis' above.)
●Diagnosis and evaluation – In practice, ET is diagnosed by the following (algorithm 1) (see 'Clinical criteria' above):
•Bilateral upper limb action tremor, with or without head or voice tremor
•Normal neurologic examination aside from tremor
•Exclusion of other causes (eg, medications (table 2), hyperthyroidism, or metabolic abnormality)
Aside from tremor, the neurologic examination should be normal. A detailed neurologic examination aims to identify abnormalities, in particular parkinsonism (eg, rigidity, bradykinesia, postural instability) or ataxia, that suggest an alternative diagnosis (algorithm 1). (See 'History and neurologic examination' above.)
Routine laboratory tests should be performed to exclude common treatable causes of enhanced physiologic tremor, including electrolytes (particularly serum calcium) and a thyroid function test. Structural brain imaging is not required in patients with typical clinical features of ET. (See 'Laboratories' above and 'Indications for brain imaging' above.)
●Role of dopamine transporter imaging – Striatal dopamine transporter imaging using ioflupane I-123 single-photon emission computed tomography (SPECT; DaTscan) is not routinely indicated in patients with typical features of ET but can be useful in select patients, such as those with subtle parkinsonism in whom the diagnosis of ET versus PD remains unclear after serial clinical evaluations. (See 'Role of dopamine transporter imaging' above.)
ACKNOWLEDGMENTS —
The UpToDate editorial staff acknowledges Ludy Shih, MD, and Daniel Tarsy, MD, who contributed to earlier versions of this topic review.