Essential Tremor

Parameter

Key Point

Definition

Isolated tremor syndrome of bilateral upper-limb action tremor, ≥3 years, without other neurological signs

Prevalence

Most common movement disorder — ~1% overall; ~5% of those >60 years (pooled prevalence 0.9%)

Age at onset

Bimodal — peaks in 2nd and 6th decades; prevalence rises sharply >70 years

Tremor type

Postural + kinetic (action) tremor; intention tremor in severe cases

Frequency

6–10 Hz (high-frequency)

Distribution

Bilateral, symmetric, distal arms/hands; may start on one side

Modifiers

Improved by alcohol; worsened by stress

Genetics

~50% family history (up to two-thirds); autosomal dominant

Pacemaker

Cerebellum and inferior olive

Examination

Normal apart from tremor (± subtle tandem-gait impairment)

Handwriting

Large, tremulous (vs micrographia in PD)

1st-line drugs

Propranolol and Primidone (~50% respond)

Refractory

DBS of VIM thalamus; focused ultrasound thalamotomy

Disorder

Definition

Tremor

Rhythmic oscillation of a body part due to intermittent muscle contractions

Dystonia

Involuntary, patterned, sustained or repeated contractions with twisting movements and abnormal posture

Athetosis

Slow, distal, writhing movements, mainly arms and hands (a form of dystonia)

Chorea

Rapid, semi-purposeful, dance-like non-patterned movements; large-amplitude proximal = ballism

Myoclonus

Sudden, brief (<100 ms), jerk-like, arrhythmic twitches

Tic

Brief, repeated, stereotyped contractions that can be briefly suppressed; simple or complex

Mechanism

Tremors

Mechanical oscillations

Physiological tremor

Reflex-based oscillations

Neuropathic tremor

Central neuronal pacemakers

Essential tremor, palatal, orthostatic, parkinsonian rest tremor, Holmes tremor

Disturbed feed-forward / feedback loops

Cerebellar tremor, Holmes tremor

Feature

Physiological Tremor

Enhanced Physiological Tremor (EPT)

Nature

Fine tremor of outstretched limbs — universal

Visible action tremor, mainly upper limbs

Frequency

7–12 Hz

8–12 Hz (same range, larger amplitude)

Origin

Heartbeat, limb mechanics, motoneuron firing, spindle-feedback synchrony

Physiological tremor amplified

Visibility

Usually only on electrophysiology / accelerometer

Seen in up to 10% of population

Triggers

Fatigue, anxiety, fear, excitement, stimulants, hyperthyroidism

Lifting weight, anxiety, fatigue, metabolic (hyperthyroidism, electrolytes), drugs (valproate, lithium), toxins (caffeine, smoking, alcohol)

Management

None

Treat the cause; beta-blocker if needed

Parameter

Data

Overall

~1% of population; ~5–10 million persons in US / Western Europe

Elderly

~5% of those >60 years (up to 10% in some series)

Meta-analysis

Range 0.01–20.5%; pooled prevalence 0.9%

Onset

Can begin in childhood; bimodal peaks — 2nd and 6th decades; dramatic rise >70 years

Presentation

Starts young, but usually manifests / presents at 60–70 years

Care-seeking

Only a fraction seek care; long latency from onset to presentation

Disability

Nearly all have social/functional/occupational disability at diagnosis; up to 25% make occupational adjustments

Aspect

Detail

Family history

~50% (Harrison) — up to two-thirds (Bradley); rises to 96% when first-degree relatives are examined directly

Inheritance

Autosomal dominant, virtually complete penetrance by age 50

Relative risk

First-degree relatives 5–10× more likely to have ET

Twin studies

Both hereditary and environmental factors matter

Loci / genes

• ETM1 (FET1) — chromosome 3
• ETM2 — chromosome 2
• DRD3 (D3 receptor) — 3q13.3
• Locus on 6p23
• GGC repeat expansion in NOTCH2NLC
• LINGO1 variant (association, unconfirmed)

Caveat

No independently confirmed causative gene; many phenocopies due to heterogeneity and high prevalence

Evidence

Finding

Pacemaker sites

Cerebellum and inferior olive — altered “tremor pacemaker”

Clinical

Cerebellar signs in ~10%; abnormal tandem gait

Lesion data

Tremor may resolve after ipsilateral cerebellar lesion

Motor control

Abnormal ballistic movements → abnormal cerebellar timing

PET / blood flow

Bilaterally increased cerebellar activity at rest and during tremor

MR spectroscopy

↓ N-acetyl-L-aspartate (NAA)/creatine in cerebellar cortex → suggests degeneration

Pathology

Purkinje cell loss, axonal torpedoes (controversial); Lewy bodies in a few autopsies

Neurochemistry

Possible degeneration of GABAergic cerebellar neurons

Feature

Essential Tremor

Type

Predominantly action tremor → postural + kinetic; intention tremor (overshoot) in severe cases

Frequency

6–10 Hz

Amplitude

Kinetic tremor amplitude > postural tremor amplitude

Laterality

Typically bilateral and symmetric; may begin on one side and remain asymmetric

Early symptom

Barely perceptible postural/action tremor of distal arms and hands

Functional impact

Interferes with eating, drinking, writing

Alcohol

Improves tremor — striking response in ~50%; helps diagnosis

Stress

Worsens tremor

Handwriting

Large and tremulous; spiral drawing shows tremor

Rest tremor

May occur late in severe ET

Site

Frequency / Note

Upper limbs (hands, forearms)

Most common — core feature

Head (titubation)

~30%; milder than limb tremor; side-to-side “no-no” type

Voice

~20%

Tongue

~20%

Face / jaw

~10%

Lower limbs

~10% — rare

Trunk

May occur

Multiple sites

~50% of patients

Domain

Finding

Cerebellar

Impaired coordination / tandem walking; mild ataxia in severe ET

Cognitive

Frontostriatal cognitive deficits

Others

Hearing, personality, mood and olfactory disturbances

Change over time

Explanation

Frequency ↓, amplitude ↑

Age-related mechanical changes in limbs and muscle

Progressive disability

True progression — severity relates to disease duration, independent of age

Severity with age

Severe, disabling tremor more likely as patient ages — often with reduced tremor frequency

Criterion

Requirement

i. Core

Isolated tremor syndrome of bilateral upper-limb action tremor

ii. Duration

At least 3 years

iii. Other sites

With or without tremor in other locations (head, voice, lower limbs)

iv. Exclusion

Absence of other neurological signs — dystonia, ataxia, parkinsonism

Aspect

Detail

Definition

ET features plus additional “soft” neurological signs (e.g., impaired tandem gait, questionable dystonic posturing, memory impairment, rest tremor)

Status

Tentatively defined, controversial; many believe ET-plus is more common than pure ET

Clinic reality

Up to 50% of clinic ET patients do not fit the “pure” picture — overlap with dystonia/parkinsonism

Step

What to do

1. Observe at rest

Hands in lap — ET: little/no tremor; PD: rest tremor

2. Posture

Arms outstretched — postural tremor (ET) appears immediately; PD re-emergent tremor after a few-seconds latency

3. Kinetic

Finger-nose, pouring water, drinking — kinetic tremor, ± terminal intention

4. Other sites

Head (no-no), voice (sustained “aaah”), jaw, tongue, legs

5. Writing & spiral

Large tremulous writing vs micrographia

6. Neuro exam

Look for bradykinesia, rigidity (distinguish cogwheeling from tremor), dystonia, ataxia

7. Tandem gait

Subtle impairment may occur in ET

8. History

Duration ≥3 years, family history, alcohol response, stress, drugs, caffeine

9. Exclude EPT causes

Thyroid status, electrolytes/metabolic, drug review (valproate, lithium), caffeine, smoking, alcohol

10. Quantify

TETRAS (Essential Tremor Rating Assessment Scale) — correlates with kinesia-based measurement

Condition

Distinguishing Features

Enhanced physiological tremor

Fine postural tremor with identifiable trigger (thyroid, drugs, anxiety, caffeine); resolves with correction

Parkinson disease

Rest tremor suppressed by action, bradykinesia with sequence effect, rigidity, micrographia, gait and postural instability

Dystonic tremor

Worse when moving toward the dystonic direction, relieved moving opposite; sensory trick (geste antagoniste); head tremor often due to cervical dystonia

Cerebellar tremor

Feedback-loop tremor — intention tremor with other cerebellar signs

Holmes tremor

Central pacemaker + feedback loop tremor

Orthostatic tremor

Central pacemaker tremor on standing

Neuropathic tremor

Reflex-based; with peripheral neuropathy

Feature

Essential Tremor

Parkinson Disease

Main tremor

Postural / kinetic

Rest

Effect of action

Worsens

Suppressed

Frequency

6–10 Hz

Lower

Onset

Bilateral, symmetric

Unilateral, asymmetric

Head / voice

Common

Uncommon (jaw/lip may occur)

Postural tremor

Immediate

Re-emergent after latency of seconds

Handwriting

Large, tremulous

Micrographia

Bradykinesia / rigidity

Absent

Present (sequence effect, cogwheeling)

Alcohol

Improves

No typical benefit

Family history

~50%, AD

Usually sporadic

Pitfall

May develop rest tremor late

May have postural tremor

Step

Management

Mild, no disability

Reassurance only

Meal-time tremor, alcohol-responsive

Small alcoholic drink before meals may help (caution: dependence)

Functional disability

First line: Propranolol or Primidone (effective in ~50%)

Partial response

Combine propranolol + primidone (may be better than either alone)

Failure / intolerance

Second-line: topiramate, gabapentin, pregabalin, alprazolam, clonazepam, acetazolamide, nimodipine

Focal hand / head / voice

Botulinum toxin injection

Severe, drug-resistant

VIM thalamus DBS or focused ultrasound thalamotomy

Aspect

Propranolol

Primidone

Class

Non-selective β-blocker

Anticonvulsant (barbiturate-like)

Efficacy

↓ amplitude in 40–50%; hand > head

~50% improvement; may be better for head tremor

Starting dose

Low doses often effective

12.5–25 mg at bedtime

Dose range

20–120 mg/day divided (Harrison); 120–320 mg/day (Bradley)

50–350 mg/day (Bradley); up to 125–250 mg TDS (Harrison); single night or divided

Adverse effects

Bradycardia, fatigue, nausea, diarrhoea, rash, impotence, depression

Acute: sedation, nausea, dizziness, vertigo, unsteadiness; long-term well tolerated

Contraindications

Asthma, bradycardia, CHF, 3rd-degree AV block, diabetes

Acute intermittent porphyria; hypersensitivity to primidone/phenobarbital. Caution: hepatic/renal impairment, respiratory depression, elderly, pregnancy

Tip

Head tremor often refractory

Start low, titrate slowly to avoid acute toxicity

Option

Notes

Topiramate

Benefit in double-blind placebo-controlled study

Gabapentin / pregabalin

Reported benefit; not widely used

Benzodiazepines

Alprazolam, clonazepam

Others

Acetazolamide, nimodipine

Botulinum toxin

Wrist flexors (hand), cervical muscles (head), voice; benefit lasts 3–4 months; risk of weakness

Pipeline

Tremor-suppression devices, peripheral nerve stimulation, GABA-A modulators, Ca-activated K-channel drugs, Cav3 T-type Ca-channel blockers

Aspect

VIM Thalamic DBS

Focused Ultrasound (FUS) Thalamotomy

Target

Ventral intermediate (VIM) nucleus of thalamus

VIM thalamus — unilateral, incisionless

Efficacy

Contralateral tremor ↓ up to 75% in up to 90%

RCT (Bond 2017, n=27, 2:1 vs sham): CRST median improvement 62% vs 22% (P = .04)

Bilateral

Possible and safe; ↑ dysarthria, gait/balance problems

Unilateral

Adverse effects

ICH, seizures, dysarthria, paraesthesia, dysequilibrium, headache, dyspraxia, word-finding difficulty

Does not require open surgery

Hardware issues

Lead fracture/migration, generator failure → reoperation

—

Candidate

Cognitively intact, otherwise healthy, disabling medication-resistant tremor

Troublesome, drug-resistant ET