Bilateral, largely symmetric postural and kinetic tremor of the hands; the most common adult movement disorder.
Overview
An isolated tremor syndrome of bilateral upper-extremity action tremor of at least 3 years' duration, with or without tremor in other locations (head, voice, lower limbs), and absence of other neurologic signs such as dystonia, ataxia, or parkinsonism (per MDS 2018 consensus).
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Risk factors
- Family history of tremor (autosomal dominant in many)
- Advancing age
- Possible environmental exposures (harmane in cooked meat, lead) — associations unproven
Pathophysiology
Pathogenesis incompletely understood but increasingly considered a network disorder centered on the cerebello-thalamo-cortical circuit. Pathologic studies show Purkinje cell loss and torpedoes in the cerebellum in many cases. Tremor frequency 4-12 Hz (typically 6-10 Hz).
Clinical presentation
Symptoms
- Hand tremor with writing, drinking from a cup, eating soup, or holding a posture
- Voice tremor produces a quavering quality, especially with sustained 'ahhh'
- Head tremor (titubation), typically yes-yes or no-no
- Often improves transiently with alcohol
- Worsened by stress, fatigue, caffeine, sleep deprivation
Signs / physical exam
- Postural tremor on outstretched arms
- Kinetic tremor on finger-to-nose testing
- No resting tremor (in pure ET)
- No bradykinesia, rigidity, ataxia, or dystonia
- Tremor may have a re-emergent component (appears after a latency when arms are held outstretched, mimicking PD)
Classic findings
Bilateral symmetric hand tremor present with action and posture, absent at rest, often with positive family history and alcohol responsiveness.
Differential diagnosis
- Parkinson disease tremor — Asymmetric resting tremor, pill-rolling, accompanied by bradykinesia and rigidity; tremor decreases with action
- Enhanced physiologic tremor — Postural tremor exacerbated by anxiety, caffeine, beta-agonists, hyperthyroidism, hypoglycemia, alcohol withdrawal
- Dystonic tremor — Irregular, jerky, position-specific tremor with a 'null point'; accompanied by dystonic posturing
- Cerebellar tremor — Coarse, low-frequency intention tremor worsening as target approached; ataxia and dysmetria
- Drug-induced tremor — Valproate, lithium, amiodarone, beta-agonists, SSRIs, methylxanthines, tacrolimus
- Wilson disease — Young adult with 'wing-beating' proximal tremor, hepatic disease, Kayser-Fleischer rings
- Functional tremor — Sudden onset, distractibility, entrainment to tested frequency, variable amplitude
Diagnostic workup
Diagnostic criteria
MDS 2018: isolated tremor syndrome of bilateral upper limb action tremor for ≥3 years, ± other locations, without other neurologic signs.
Labs
- TSH to exclude hyperthyroidism
- BMP and glucose if metabolic causes suspected
- Ceruloplasmin if age <40 to rule out Wilson disease
- Medication review for tremorogenic drugs
Imaging
- Brain imaging not routinely required — order MRI only if focal findings or atypical features
- DaTscan SPECT can distinguish ET from PD when uncertain (normal in ET, abnormal in PD)
Treatment
First-line
- Propranolol 60-320 mg/day (non-selective beta-blocker) — first-line, may need long-acting formulation; contraindicated in asthma, severe bradycardia, decompensated HF
- Primidone 25-250 mg/day, titrated slowly — comparably effective to propranolol; common acute first-dose toxicity (sedation, ataxia, nausea) often abates
- Combination of propranolol + primidone for refractory disease
- Lifestyle: reduce caffeine, manage stress, ensure adequate sleep
Refractory or severe disease
- MR-guided focused ultrasound (MRgFUS) thalamotomy of Vim — incisionless, FDA-approved for medication-refractory ET (typically unilateral)
- Deep brain stimulation of ventral intermediate nucleus (Vim DBS) — for bilateral, severe, or younger patients
- Botulinum toxin injection — selected role for head/voice tremor
Second-line / adjunct
- Topiramate (good evidence)
- Gabapentin, alprazolam (second-line oral options)
- Atenolol, sotalol, nadolol (alternative beta-blockers, less evidence)
Complications
- Functional disability — handwriting, feeding, drinking, fine motor tasks
- Social embarrassment and avoidance
- Depression
- Possible mild cognitive impairment and increased risk of dementia in late-onset disease
- Surgical complications: dysarthria, gait imbalance, paresthesias (DBS or thalamotomy)
PANCE pearls
- ET typically improves with alcohol — a useful historical clue but not a treatment.
- Rest tremor argues for Parkinson disease; isolated head tremor argues for dystonic tremor.
- Primidone has profound first-dose effects — warn patients and start at 12.5-25 mg at bedtime.
- Beta-blockers reduce amplitude more than frequency — perfect smoothing should not be expected.
- DaTscan can be reimbursed and is useful when distinction from PD changes management.
References
- MDS 2018 — Bhatia KP et al. Consensus Statement on the Classification of Tremors. Mov Disord 2018;33:75-87.
- AAN 2011 — Zesiewicz TA et al. Evidence-based guideline update: Treatment of essential tremor. Neurology 2011;77:1752-1755.
- MRgFUS Pivotal Trial — Elias WJ et al. A randomized trial of focused ultrasound thalamotomy for essential tremor. NEJM 2016;375:730-739.
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