Version May 2024
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 the cerebellum and brainstem (locus ceruleus) have been most commonly implicated [24-33]. 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 [34]. 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 [35].
CLINICAL FEATURES
Tremor characteristics — ET is an action tremor that classically affects the hands and arms, is typically bilateral, and is often slightly asymmetric. It can also affect the head, voice, and less commonly the face or trunk.
Tremor is activated by voluntary movement or when the arms are held in a fixed posture against gravity. ET becomes immediately apparent in the arms when they are held outstretched and is often amplified by goal-directed movements such as drinking from a glass or finger-to-nose testing. Tremor is absent when the affected body part is fully relaxed and supported against gravity. At times, action tremor may overflow into a limb or other body part when not completely relaxed, giving the appearance of a rest tremor.
Tremor frequency is typically moderate to high (6 to 12 Hz), although there is considerable variability [36,37]. The type of tremor in ET may vary from a low-amplitude, high-frequency postural tremor of the hands to a much larger-amplitude tremor that is activated by particular postures and actions.
Tremor of the head in patients with ET may be vertical ("yes-yes") or horizontal ("no-no") and is usually associated with tremor of the hand or voice [38]. According to diagnostic criteria, isolated head or voice tremor is exclusionary for ET [39]. Isolated head tremor often suggests the possibility 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 'Spasmodic dysphonia' below.)
Lower limb tremor is highly unusual in ET and often suggests Parkinson disease (PD). (See 'Parkinson disease' below.)
Exacerbating and relieving factors — Patients with ET can develop enhanced physiologic tremor due to anxiety, excitement, or other adrenergic stimulation, thereby worsening the underlying tremor. In contrast to physiologic tremor, ET is not usually exacerbated by caffeine. ET is typically relieved by small amounts of 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" [39,40]. (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 [41-44], and that ET may be associated with an increased risk of dementia [45,46].
Natural history — ET tends to worsen gradually over time. Symptoms of ET are often present for years to decades before patients seek medical attention.
The course is generally slowly progressive, but may be exacerbated by anxiety, medical stressors, or new medications. There may sometimes appear to be a stepwise worsening of tremor, perhaps due to other contributing 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 often significant, as it very typically affects writing, signing of checks and other documents, using tools or eating utensils, and holding drinks. (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 have a symmetrical, very 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 proclivity to demonstrate mild, nondisabling physiologic tremulousness.
Many factors can enhance physiologic tremor to the point of detection, most often by increasing sympathetic activity. Common factors that lead to enhanced physiologic tremor are stress, anxiety, excitement, muscle fatigue, fever, hypoglycemia, alcohol or opioid withdrawal, and a variety of medications, drugs, and substances (table 2). (See "Overview of tremor", section on 'Physiologic tremor'.)
Resolution of enhanced physiologic tremor with removal of the precipitating factor distinguishes it from ET. The duration of tremor is also useful, as patients typically report a much shorter duration of enhanced physiologic tremor than of ET.
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.
In its classic form, tremor due to Parkinson disease (PD) is a rest tremor and at onset typically begins unilaterally, which distinguishes it from ET (table 3). The absence of rest tremor is generally reassuring that tremor is due to ET and not PD, especially combined with an otherwise normal neurologic examination (ie, no bradykinesia or rigidity).
However, some overlap exists. Patients with PD can have a rapid postural or action tremor indistinguishable from ET [47]. In fact, it is not unusual for patients with PD to present with a postural tremor shortly before they display other signs of PD. The presence of subtle bradykinesia, rigidity, or micrographia in early cases of parkinsonian postural tremor supports the diagnosis of PD, although these signs may not appear until later. In addition, a tremor of the same frequency and amplitude as the rest tremor may emerge after a latency during posture holding (the so-called re-emergent tremor). By contrast, ET is apparent immediately with a posture-holding maneuver.
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 limb cogwheel rigidity, 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.
Evaluation for classic motor signs of PD (bradykinesia, rigidity, gait, and nonmotor features such as rapid eye movement [REM] sleep behavior disorder and hyposmia) will further distinguish PD from ET. Additional characteristics of tremor in patients with PD are reviewed separately. A handwriting and drawing sample are helpful in distinguishing ET from PD. (See "Clinical manifestations of Parkinson disease", section on 'Tremor'.)
Dystonic head tremor — When head tremor occurs in relative isolation, without action tremor in the upper limbs or signs of cerebellar dysfunction, the possibility of dystonic head tremor due to cervical dystonia (spasmodic torticollis) should be considered.
Cervical dystonia is the most common isolated focal dystonia and typically leads to head rotation (torticollis), tilt (laterocollis), flexion, or extension. Tremor of the head is common in cervical dystonia, in which it may be due either to a coincidence of ET and cervical dystonia or to a manifestation of dystonic muscle spasm. Cervical dystonia may also present primarily as an isolated head tremor, with minimal pain, stiffness, or deviation of the head.
Head tremor due to cervical dystonia tends to be more irregular and jerky than ET-related head tremor and increases with various changes in head position, most often when rotating the head away from the side of torticollis. ET-related head tremor usually subsides with the head supported on a pillow, while in cervical dystonia head tremor often persists in the reclining position. (See "Etiology, clinical features, and diagnostic evaluation of dystonia", section on 'Cervical dystonia'.)
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 [48]. In addition, other signs of dystonic tremor include emergence with specific positions (eg, head turn, neck flexion-extension) or tasks (eg, writing). Posture of the head 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.
Spasmodic dysphonia — Voice tremor may be a manifestation of ET but rarely occurs in isolation; when it does, it is important to differentiate it from 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 essential tremor, the voice sounds unstrained and quavering; with spasmodic dysphonia, the vocal tremor is accompanied by hoarseness, straining, a strangulated quality, or voice breaks. (See "Etiology, clinical features, and diagnostic evaluation of dystonia", section on 'Laryngeal dystonia'.)
Other action tremors — Cerebellar outflow tremor should be considered when the tremor oscillations increase steadily before arriving at the target rather than at the termination of goal-directed activity. For example, ET-related tremor is often mild or even absent during the course of finger-nose testing but will first appear or increase within a few seconds after reaching the target. However, a distinction between the two is often difficult. The presence of ataxia, dysmetria, proximal distribution of the tremor, or wide-based and ataxic gait usually suggests a cerebellar disorder as a cause of tremor rather than ET. However, mild cerebellar signs are present in some severe forms of ET [49]. (See "Overview of tremor", section on 'Cerebellar tremor'.)
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'.)
EVALUATION — ET is a clinical diagnosis, and the goal of the evaluation is to identify characteristic features of ET and to recognize any atypical features that may suggest an alternative cause of tremor.
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) [50]. 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 a thyroid function test. 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 not required in patients with typical clinical features of ET. 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.
DIAGNOSIS — The diagnosis of ET is purely based on clinical features [51]. Dopamine transporter imaging is useful in selected patients but is not necessary to diagnose ET in the majority of patients.
Clinical criteria — Diagnostic criteria from the International Parkinson and Movement Disorder Society (IPMDS) task force define ET by the following four features [39]:
●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 [39]. (See '"Soft" neurologic signs' above.)
Previous criteria for ET recognized family history of ET and beneficial response to alcohol as secondary criteria [52]; while these are common in patients with ET, the IPMDS felt that they were not consistent enough to include in the definition [39].
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 necessary or indicated 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 nonphysiologic 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 is often slightly asymmetric. It can also affect the head, voice, and less commonly the face or trunk. The tremor affects common daily activities such as writing, drinking from a glass, and handling eating utensils. (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.)
●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.)
●Evaluation – ET is a clinical diagnosis. 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.)
●Diagnosis – Diagnostic criteria define ET as an isolated tremor syndrome consisting of bilateral upper limb action tremor; at least three years in duration; with or without head, voice, or lower limb tremor; and absent other neurologic signs such as dystonia, ataxia, or parkinsonism. (See 'Clinical criteria' 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 selected 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.
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