Essential tremor is a common disorder affecting ~1% of the general population and ~5% of the population over 65 years of age. The disorder is currently viewed as a syndrome, with varying aetiologies¹.

An approximately symmetric postural or kinetic tremor involving the hands and forearms is mandatory for the diagnosis. It should be noted that mild, clinically detectable tremor is highly prevalent among normal control subjects/

Definition includes the following¹:

1. Isolated tremor syndrome of bilateral upper limb action tremor 
2. Duration of more than 3 years
3. With or without tremor in other locations (e.g., head, voice, or lower limbs)
4. Absence of other neurological signs (e.g. dystonia, ataxia and Parkinsonism) which could explain the tremor.

Alcohol responsiveness and family history are not sufficiently consistent to aid the definition of ET. Largely, the diagnosis of ET is based on excluding distinctive tremor types rather than asserting what is the tremor of ET².

There is ongoing uncertainty about the meaning of clinically detectable additional findings in subgroups of ET, such as mild dystonic or ataxic signs. Therefore the new classification proposes to keep these subgroups as a separate entity called ‘Essential tremor plus’ which is defined as tremor with the characteristics of ET and additional neurological signs of uncertain significance such as impaired tandem gait, tremor at rest, questionable dystonic posturing, memory impairment or other mild neurological signs of unknown significance¹.

ORIGIN

The pathophysiology of essential tremor has been linked to abnormal, oscillatory activity within the cortico-olivo-cerebello-thalamic circuit³. Oscillations are then transmitted to the spinal motor neuronal pool, and coherence for both proximal and distal muscles between cortex and the motor unit has been demonstrated.

The relatively stable tremor in essential tremor may fit with a single oscillator, that is, the inferior olive or deep cerebellar nuclei, although there is increasing scepticism about the role of the inferior olive in ET⁴.  Evidence supporting this network hypothesis include lesion analysis (a lesion of the cerebellum or its outflow tracts can abolish the tremor in ET patients almost completely) and the success of VIM DBS for alleviating ET.

CLASSIFICATION

There are very different approaches to understanding ET:

• Classical ET, as a monosymptomatic disorder (due a dynamic oscillatory disturbance of the motor system), and
• Second, a heterogeneous disorder, the ETs, seen as a family of diseases (a more complex and heterogeneous degenerative disorder).  Other motor features described in patients with ET are gait ataxia, postural instability and eye-motion abnormalities. There is clinical and electrophysiologic evidence of a pancerebellar disturbance in patients with some forms of ET.

The main phenotypes of ET are:

• Classical ET with hand tremor.

ET may be considered to be a prototypical syndrome of an isolated action tremor.

• ET with head tremor (25%):

Head movements occur in a vertical or horizontal plane (yes/yes and no/no tremor). Postural tremor may occur in the head in about 40% of patients with ET. Typically, the head tremor is a postural tremor which resolves at rest, that is, the tremor abates in the supine position. Head tremor is more often present in patients with disease of long duration, and is six times more common in women than men.

• ET with jaw tremor:

Jaw tremor is present in 10-20% of ET cases with persistent rest tremor and 10% of cases without rest tremor. ET patients with jaw tremor tend to be older, and have a more clinically severe and widespread disorder.  The tremor is predominantly a postural tremor (occurring during voluntary mouth opening) or kinetic tremor (occurring while speaking). A small number of patients may also exhibit mild tremor while their mouth is closed; however, in these it can be difficult to determine whether the jaw is fully relaxed. Overall, jaw tremor is uncommon in patients with ET, and it is important to note that jaw tremor is well recognized in PD and is also seen in dystonia.  (Jaw tremor may also be associated with neuroleptic treatment, and there is also a high frequency isolated jaw tremor of 14-16 Hz.)

• ET with tongue and voice tremor (15%):

Frequently tremor in these regions occurs in association with hand tremor. These midline tremors occur in patients with long-standing ET affecting the upper limbs, with older age and female gender appearing to be risk factors. Many patients with isolated voice tremor do not have ET, but suffer from laryngeal dystonia.

• ET with trunk and leg and feet tremor:

This is an infrequent form of tremor with kinetic leg tremor seen in fewer than 10% of patients.

• The largest subgroup of patients is the one with aging-related tremor. Therefore, one important cause of tremor may be a form of aging presenting with tremor as a main symptom; this is reviewed further under differential diagnosis in this section on ET.

CLINICAL FEATURES

The tremor of ET is typically a kinetic tremor (ie,a tremor during voluntary motion) most commonly affecting the arms and hands, often with a postural component. The central clinical feature of ET is kinetic tremor. This is generally observed during various activities of daily living, ranging from eating to writing, and may be elicited on neurologic examination during a variety of manoeuvres (eg, finger-nose-finger test, spiral drawing, pouring water between two cups)⁵.

When rest tremor is present, it will increase during movement onset in about half the patients, and stay the same in the remainder, and will not decrease or disappear as in PD⁶.

Frequency: Typically, tremor has a frequency of from 4 to 12 Hz in the arms without any other neurological signs.  The frequency of tremor is inversely related to age, with older patients generally having the slowest tremor frequencies. Amplitude, and to a lesser extent, frequency can vary, and change with different tasks.

Symmetry: Although ET is classically a symmetrical tremor, the arm tremor of ET may be mildly to moderately asymmetric (30% of cases have asymmetry of more than 50%). 

Regularity: Tremor in early ET may be jerky and intermittent, and some types may be myoclonic and jerky many years still after tremor onset.

Presentation: ET may start with a postural tremor that can still be suppressed during goal- directed movements, resulting in a non-disabling tremor, and as a result, many ET patients are never seen by a neurologist.

Task related difficulties such as with eating and drinking are typical of ET.  Tremor may be suppressed by performing skilled manual tasks, and tremor resolves when the body part relaxes as well as during sleep.

The tremor of ET may improve with alcohol intake (50-75% of patients), but alcohol responsiveness is not specific for ET since other tremors, such as dystonic tremor, may improve as well. Alcohol-responsive patients may also experience a “rebound” period, typically 3 to 4 hours after consumption, during which time there is worsening of the tremor.

A number of subtle abnormalities may also be found in ET, which can be grouped into:

• Cerebellar disturbances with a mild disturbance of tandem gait, subclinical oculomotor disturbances, a mild extremity dysmetria and disturbances of timing.
• Neurodegeneration or faster aging, e.g. shortened life expectancy or higher incidence of cognitive decline (mild cognitive difficulty through to frank dementia)⁷.

TREMOR TYPES

Amongst ET subjects, tremor need not necessarily be present for all tremor types.

• Postural tremor in ET can involve oscillations around several joints, including the shoulder joint, elbow, wrist and fingers, whereas in PD, the more distal structures (especially fingers) are more typically involved. The postural tremors in the right and left arm are out of phase; when the two hands are held together (e.g., while holding a cup), this dampens the tremor. There tend to be flexion–extension movement of the hand/arms and adduction–abduction movement of the fingers, with greater tremor at the wrist than at the MCP joints.  In ET, tremor usually has a lower frequency in the proximal parts of the body than in the distal parts.
• Kinetic tremor is more severe than postural (which may be absent).  Indeed, the opposite pattern (postural tremor in excess of kinetic tremor) may be a clue that the diagnosis is not ET. As tested using manoeuvres such as pouring, using a spoon, drinking, finger-nose testing, and drawing spirals, the amplitude of kinetic tremor is significantly higher than that of the postural tremor.  Kinetic tremor often increases markedly in the final phase of goal-directed movements, and is then similar to the intention tremor which is often viewed as being characteristic of cerebellar disease.
  • Intention tremor is associated with slowing of the frequency and an increase in tremor amplitude, particularly with advancing age, together with signs of cerebellar dysfunction such as movement overshoot and slowness of movements. Intention tremor is found in about 50 % of patients, its severity correlates with duration of tremor, and it develops over a wide range (3-30 years) after the onset of postural tremor.
  • Kinetic leg tremor is also seen in ET (toe-finger manoeuvre) (associated with advanced age, head tremor and duration of disease).  Intention tremor may also be present in the chin and neck when attempting to drink or eat from a spoon. 

• Rest tremor is present in about 20% of ET patients in movement disorder clinics, and is probably much less common in the general ET population. Rest tremor is typically seen in patients with advanced ET and is never the presenting sign of ET. Rest tremor of the leg is virtually never compatible with a diagnosis of ET. Rest tremor generally decreases in ET when the patient is walking. The development of isolated rest tremor (i.e., rest tremor without rigidity or bradykinesia) in advanced ET does not mean that the patient has developed PD in addition to ET.

SPECIFIC EXAMINATION FEATURES

(vv)ExaminationpatientET.mp4(tt)

Examination of patients with Essential Tremor⁶

• Action Tremor seen with hand rotation: it is relatively easier to see action tremor while the patient is rotating their hands, rather than simply maintaining a posture.
• Postural tremor seen with wing-beating posture: postural tremor in ET is dependent on limb positioning, with tremor in the wing-beat position being greater than when the arms are held outstretched in the prone position; this posture is associated with a see saw effect due to the tremor being out of phase.
• Froment’s manoeuvre: tone at the wrist is frequently increased when assessed with Froment’s manoeuvre (contralateral movement of the limb), and cogwheeling may also be noted.   
• In patients with rest tremor: assess resting tremor suppression by a voluntary movement (and to test for tremor re-emergence thereafter), wrist extension is often more suitable than the other postures, because this movement can be done rapidly (see video)⁸.
• Bradykinesia may be difficult to judge in the presence of moderate to severe tremor.       
• Head tremor in the complete absence of arm tremor is either never seen or is highly unusual in ET, and isolated head tremor is frequently associated with spasmodic torticollis: see Dystonic Tremor. Head tremor will be exacerbated in the majority of patients following a phonation task ( saying “ahh” or “eee” for 10-15 seconds).

(vv)4RapidmovementandRETinPD.mp4(tt)

To assess resting tremor suppression by a voluntary movement (and to test for tremor re-emergence thereafter), wrist extension is often more suitable than the other postures, because this movement can be done rapidly.

WRITING AND DRAWING

With respect to generation of a spiral, ET patients are more likely to demonstrate a single predominant axis as compared to dystonic tremor. The ET tremor often has an intentional component at the moment of initiation of the spiral.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

In ET, spirals drawn with the right hand typically have a single identifiable tremor orientation axis (i.e., tremor is most severe at 1-2 o'clock), whereas those drawn with the left hand have a single identifiable tremor orientation axis that is 90° to that on the right (i.e., tremor is most severe at 10–12 o'clock)9.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

(A) The Archimedes spiral shows a unidirectional tremor axis in the 8–2 o’clock direction, suggesting essential tremor, but it is not clear whether the amplitude and frequency are constant. The line drawn perpendicular to the tremor axis emphasises the amplitude and makes it easier to discern that it is also constant, as is the frequency9.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

(B) The handwriting is tremulous and potentially compatible with either essential tremor or dystonic tremor. The spirals show a unidirectional 8–2 o’clock axis on the right, and a 10–4 o’clock axis on the left, symmetrical in size and severity—all features that point towards essential tremor. However, the regularity of the amplitude and frequency is difficult to determine from the spirals as the severity of the tremor causes the turns to overlap. The straight line drawings demonstrate that the amplitude, frequency and axis are all constant. The left (dominant) handed vertical line has 18 oscillations drawn over 2 s, giving an estimated frequency of 9 Hz9.

 

 

 

 

 

 

  

 

 

 

 

 

 

 

 

 

 

 

 

 

(C) Spiral drawings from a patient with severe essential tremor showing large tremor oscillations with a unidirectional axis, fairly regular amplitude and frequency, and symmetry between the hands. An enlarged spiral is sometimes seen in severe essential tremor, perhaps reflecting ataxia that may occur as part of the disorder, or to compensate for the size of the penstroke undulations10.

 

 

 

 

 

 

 

 

 

 

One method to clarify tremor variability is to ask the patient to draw a line at a steady rate and in a direction perpendicular to the tremor axis of the spiral (see figure B above). A longer tracing of the tremor makes it easier to see whether the amplitude and frequency are constant (usual in essential tremor) or variable (more suggestive of dystonic or functional tremor).

AGE OF ONSET

Hereditary ET is fully penetrant by 65 years and all forms of ET have a bimodal age of onset with peaks in the 2nd and 6th decade. This suggests the existence of at least two different pathophysiologic entities, potentially with different courses.  There is an undefined boundary between senile tremor and the reported distinct second epidemiological age peak of ET: see Senile Tremor in the section on Differential Diagnosis, below. Many elderly patients retrospectively recall the onset of tremor as young adults, but then a long period of relative stability with mild tremor (i.e., a plateau), followed by a relatively rapidly progressive worsening of tremor in the seventh or eighth decade of life¹¹.

PROGNOSIS

The late-onset ET group may be associated with nonmotor symptoms possibly representing the transitional manifestations to developing PD, dementia and postural impairment.  Predictive factors of greater severity include older age, longer disease duration, and the presence of voice tremor.Fewer than 10% of patients with long disease duration in a cross sectional study were completely unable to drink or use a spoon, although there is a progressive decline in function over decades. 

DISTRIBUTION

Upper limbs >> head >> voice >> face/jaw >> tongue >> trunk >> lower limbs

Lower limb tremor occurs in classic ET but is typically mild and asymptomatic. Rest tremor in the lower limbs is not a feature of ET, even when there is rest tremor in the hands. 

DIAGNOSIS

The core features are bilateral postural tremor of the forearms, with or without additional kinetic tremor. No other neurological signs should be present, apart from Froment's sign. However, note that many patients will show difficulty with tandem gait, and intention tremor that is indistinguishable from cerebellar disease.

DIFFERENTIAL DIAGNOSIS

See Table: Types of Tremor note that misdiagnosis of ET is common, and that, in particular, dystonia is frequently misdiagnosed as ET. 

Isolated focal, position-specific, and task-specific tremors are not likely to be ET and are often associated with subtle dystonia (see section on dystonic tremor).

Features that are not typical of ET are:

1. Unilateral arm tremor
2. Isolated head or leg tremor
3. Re-emergent tremor
4. Presence of a null point or sensory trick
5. Tremor directionality
6. Reduced arm swing

• Parkinson's Disease: Patients presenting with late onset asymmetrical postural tremor with or without mild rest tremor may be diagnosed as having essential tremor, but typically develop into PD after an about 15 years. These patients may have both alcohol sensitivity and a family history¹².
• Enhanced physiologic tremor: 8% of healthy elderly people have an enhanced physiologic tremor that is electrophysiologically similar to mild ET. Enhanced physiologic tremor is usually of low amplitude and high frequency, predominantly a postural tremor. This tremor can be difficult to differentiate from essential tremor because it may responds to first line agents given for ET and is often alcohol responsive. In difficult cases, physiological testing can be helpful in distinguishing the two types of tremor.

• Senile Tremor: Also called Age Related Tremor (ART), and also called late-onset upper limb action tremor. This tremor is an action tremor that affects the upper limb(s) (as evident in spirals).  There is an increasing prevalence of tremor from the 8th to the 10th decades, from approximately 25% in the 8th decade to 50% by the 10^{th 13}.

  Tremor in people aged 70 years or older is associated with an increase in morbidity and mortality, which is not established to be a feature of ET; in addition, the incidence of ET declines after the 7^th decade. This is controversial, since there is an undefined boundary between senile tremor and the reported distinct second epidemiological age peak of ET. 
• Spinocerebellar ataxia type 12. 

  (vv)SCA12.mkv(tt)

The video is a nice illustration of the difficulties distinguishing between some forms of spincocerebellar ataxia and ET ^14 15. SCA 12, predominantly identified in patients of North Indian origin, is typically characterized by an action tremor of the head and upper limbs. They may also also have gait ataxia, hyperreflexia and parkinsonism. MRI shows widespread cerebral and cerebellar atrophy.

• Fragile X tremor-ataxia syndrome: see section
• Cortical tremor a form of rhythmic cortical myoclonus.
• Benign tremulous parkinsonism: most cases are due to underlying PD.

DIAGNOSTIC TESTS

On the whole, no specific tests are required, and ET is, to some extent, a diagnosis of exclusion.

Tests that may be performed include:

1. Spiral drawing before and after alcohol.
2. Tandem gait: More than three missteps over 10 metres.

NEUROPHYSIOLOGICAL CRITERIA FOR ET¹⁶

1. Rhythmic burst of postural tremor on EMG.

2. Tremor frequency > 4 Hz.

3. Absence of rest tremor, or, if rest tremor is present, frequency 1.5 Hz lower than the postural tremor.

4. Absence of tremor latency from rest to postural position (>2 s).

5. Changes of the dominant frequency peak to less than or equal to 1 Hz after the weight load test. ET is therefore characterized by a tremor frequency which does not change significantly with loading (due to a fixed central oscillating mechanism).

6. No changes in tremor amplitude after mental concentration.

TREATMENT

Medical treatment leads to a reduction of tremor symptoms in 50% of patients but rarely to complete disappearance of tremor symptoms. Medical treatment often has a better effect in patients with low amplitude tremor than for individuals with high amplitude tremor. Intention tremor has a major impact on patients’ disability, but intention tremor responds less well to medication than pure postural tremor.

• In young patients propranolol is the medication of choice, (20–240 mg daily dosage).
• In older patients primidone 62.5–500 mg (daily dosage) may be effective. Acute toxic reaction to primidone with drowsiness, ataxia and dizziness can be reduced or avoided by slowly increasing medication (starting dose 62.5 mg in the evening and slow increase).
• Propranolol and primidone can be given in combination (each increased to the highest tolerated dose).

Medications of second choice include topiramate (50–300 mg) and non-selective b-blockers such as metoprolol.

See also:

Martino, D., Espay, A., Fasano, A. and Morgante, F. (2016). Disorders of Movement. Berlin, Heidelberg: Springer Berlin Heidelberg. Guidelines from this reference are found here¹⁷: ET Meds Guideline

Gironell, A. & Kulisevsky, J. Review: Diagnosis and management of essential tremor and dystonic tremor. Ther. Adv. Neurol. Disord. 2, 215–222 (2009)¹⁸.

Ferreira JJ, Mestre TA, Lyons KE, et al. MDS evidence-based review of treatments for essential tremor. Mov Disord. 2019;34(7):950-958¹⁹.   MDS evidence based review of treatments for essential tremor

Surgical treatments include:

1. Deep brain stimulation (DBS)

2. Radiofrequency (RF) thalamotomy

3. Gamma knife radiosurgical (GKRS) thalamotomy

4. Focused ultrasound (FUS) thalamotomy.

 

Comparison of Surgical Outcomes for ET²⁰.

 

 

 

 

 

 

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