Tremor
Tremor
What You'll Learn
- Classification: rest tremor vs. action tremor (postural, kinetic, intention, task-specific); 2018 consensus uses Axis 1 (clinical) + Axis 2 (etiology)
- Essential tremor: most common pathologic tremor; bilateral action tremor 6–12 Hz (slows with age), upper limbs > head > voice; AD inheritance; alcohol-responsive
- PD tremor: unilateral rest tremor 4–6 Hz, pill-rolling; re-emergent postural component; asymmetric onset
- ET first-line: propranolol (60–320 mg/d) or primidone (target 250–750 mg/d, start 12.5–25 mg qhs); DBS of VIM thalamus for refractory cases
- Holmes tremor: rest + postural + intention, <5 Hz; midbrain lesion (rubral area); delayed onset weeks–months after lesion
- DaTscan: abnormal in PD (dopaminergic deficit) vs. normal in ET — key differentiator when clinical exam is equivocal
HighYield Pearls
- Essential tremor: bilateral action/postural tremor (6–12 Hz), hands > head > voice, AD family history, alcohol-responsive (~50–75%); first-line propranolol or primidone; DBS of VIM thalamus for refractory cases
- Parkinsonian rest tremor: unilateral/asymmetric onset, 4–6 Hz pill-rolling at rest, jaw/chin involvement, abnormal DaTscan, levodopa-responsive; re-emergent postural component
- Dystonic tremor: irregular, jerky, asymmetric tremor with a null point and sensory trick (geste antagoniste); head tremor at rest favors dystonic tremor over ET
- Cerebellar/intention tremor: amplitude increases approaching the target, accompanied by dysmetria and ataxia, ipsilateral to lesion; MS (young adults), stroke, SCA, paraneoplastic; no reliably effective drug
- Holmes (rubral) tremor: proximal, large-amplitude, low-frequency (<5 Hz) rest + postural + intention tremor with delayed onset after a midbrain/thalamic lesion; try levodopa, clonazepam
- Orthostatic tremor: high-frequency 13–18 Hz on surface EMG, leg unsteadiness on standing that resolves with walking/sitting/leaning; clonazepam first-line (primidone/gabapentin alternatives)
- Functional (psychogenic) tremor: variable frequency/amplitude, abrupt onset, distractibility and entrainment are the most reliable signs; normal DaTscan
- Drug-induced tremor: lithium and valproate are the most board-tested; also β-agonists, SSRIs, amiodarone, neuroleptics (tardive/parkinsonian); enhanced physiologic tremor reverses on drug withdrawal
- FXTAS: older man + intention tremor + ataxia + parkinsonism + MCP sign on MRI → test FMR1 premutation (55–200 CGG repeats)
🔍 Quick ReferenceClinical · Activation pattern · Treatment / pearls
Clinical phenotype
- Pill-rolling, unilateral rest tremor → Parkinson disease
- Bilateral hand tremor + “yes-yes”/“no-no” head tremor, alcohol-responsive, AD family history → essential tremor
- Irregular, jerky tremor with a null point + sensory trick (geste antagoniste) → dystonic tremor
- Tremor amplitude increases as finger approaches target + dysmetria/ataxia → cerebellar (intention) tremor
- Rest + postural + intention tremor in same limb with delayed onset after midbrain stroke → Holmes (rubral) tremor
- Leg unsteadiness on standing that improves with walking or leaning on a wall → orthostatic tremor
- Variable, distractible tremor with entrainment to contralateral tapping → functional (psychogenic) tremor
- Older man + intention tremor + ataxia + parkinsonism + MCP sign on MRI → FXTAS (FMR1 premutation)
- Ear click + palatal movement, normal MRI → essential palatal tremor (tensor veli palatini); palatal tremor + olivary pseudohypertrophy on MRI → symptomatic palatal tremor (Guillain–Mollaret triangle lesion)
Activation pattern / frequency
- Rest tremor, 4–6 Hz → Parkinsonian tremor
- Postural + kinetic (action) tremor, 6–12 Hz (slows with age) → essential tremor
- Intention tremor (terminal worsening), 3–5 Hz, ipsilateral to lesion → cerebellar tremor
- Rest + postural + intention combined, <5 Hz → Holmes tremor
- High-frequency 13–18 Hz coherent bursts on surface EMG while standing → orthostatic tremor (fastest tremor in neurology)
- Fine bilateral postural tremor 8–12 Hz → (enhanced) physiologic tremor
- Task-specific tremor activated only by writing → primary writing tremor
- Variable frequency, variable burst duration on EMG, entrainable → functional tremor
Treatment / pharmacology pearls
- Propranolol or primidone (Level A) ± topiramate/gabapentin; VIM thalamus DBS or MRgFUS for refractory → essential tremor
- Levodopa-responsive; DBS target STN or GPi → Parkinsonian tremor (contrast with VIM target in ET)
- Botulinum toxin (especially cervical), trihexyphenidyl, clonazepam; GPi DBS → dystonic tremor
- Clonazepam first-line; gabapentin, valproate; often refractory → orthostatic tremor
- Levodopa + clonazepam + propranolol trial; often disappointing → Holmes tremor
- Lithium, valproate, β-agonists (albuterol), SSRIs, amiodarone, neuroleptics, corticosteroids → drug-induced / enhanced physiologic tremor (reverses on withdrawal)
- Check TSH, ceruloplasmin (<50 yr), FMR1 (older men with ataxia + tremor + MCP sign) → reversible/genetic mimics of ET
- Alcohol improves tremor (~50–75%) → essential tremor (does NOT help PD tremor — classic boards differentiator)
Tremor Classification
2018 Consensus Statement (IPMDS Task Force)
- Axis 1 — Clinical features: body distribution, activation condition, frequency, associated signs
- Axis 2 — Etiology: acquired vs. genetic vs. idiopathic
- Replaces prior classification (e.g., “benign essential tremor”); emphasizes tremor syndromes over single diseases
- ET redefined: isolated bilateral upper limb action tremor ≥3 yr duration without other neurological signs
- ET plus: ET with additional soft signs (rest tremor, impaired tandem gait, mild memory impairment, questionable dystonic posturing)
Rest vs. Action Tremor
| Category | Definition | Classic Example |
|---|---|---|
| Rest tremor | Occurs in a body part fully supported against gravity, muscles not voluntarily activated | Parkinson disease (4–6 Hz pill-rolling) |
| Postural tremor | Occurs while voluntarily maintaining a position against gravity | Essential tremor (arms outstretched) |
| Kinetic tremor | Occurs during voluntary movement (simple kinetic = any movement) | ET, cerebellar tremor |
| Intention tremor | Amplitude increases approaching the target (terminal kinetic) | Cerebellar lesion (finger-to-nose) |
| Task-specific tremor | Only during specific skilled activities | Primary writing tremor |
| Isometric tremor | During muscle contraction against a rigid stationary object | Squeezing examiner’s fingers |
Frequency Ranges
| Frequency | Tremor Types |
|---|---|
| <4 Hz | Holmes tremor, cerebellar tremor |
| 4–6 Hz | Parkinsonian rest tremor, Holmes tremor |
| 6–12 Hz | Essential tremor (typically 6–12 Hz, slows with age), enhanced physiologic tremor |
| 8–12 Hz | Physiologic tremor, enhanced physiologic tremor |
| 13–18 Hz | Orthostatic tremor |
💎 Board Pearl
- 2018 consensus eliminated the term “benign essential tremor” — ET is NOT benign (causes significant disability)
- “ET plus” is a new category for patients with ET plus additional soft neurological signs that do not meet criteria for another tremor syndrome
Essential Tremor
Clinical Features
- Most common pathologic tremor; prevalence ~1% (up to 5% in age >65)
- Bilateral action tremor (postural + kinetic) of the upper limbs, usually symmetric
- Frequency: typically 6–12 Hz (slows with age); amplitude increases, frequency decreases with age
- Body distribution: hands (95%) > head (34%) > voice (12%) > jaw/face > lower limbs
- Head tremor: “yes-yes” (vertical) or “no-no” (horizontal); absent at rest
- Alcohol responsiveness: ~50–75% improve with ethanol — hallmark feature (temporary, rebound worsening)
- Family history positive in ~50%; autosomal dominant with variable penetrance
- Duration criterion: ≥3 years of bilateral upper limb action tremor
ET vs. Parkinsonian Tremor
| Feature | Essential Tremor | Parkinsonian Tremor |
|---|---|---|
| Type | Action (postural + kinetic) | Rest tremor (re-emergent postural) |
| Frequency | 6–12 Hz (slows with age) | 4–6 Hz |
| Symmetry | Bilateral, relatively symmetric | Unilateral onset, asymmetric |
| Body part | Hands > head > voice | Hands > jaw/chin > legs |
| Head tremor | Common (~34%) | Rare |
| Jaw / chin tremor | Uncommon (helps distinguish from PD) | Common (typical PD finding) |
| Alcohol effect | Improves (~50–75%) | No significant effect |
| Writing | Large, tremulous | Small (micrographia) |
| Associated signs | None (isolated) | Bradykinesia, rigidity, postural instability |
| DaTscan | Normal | Abnormal (reduced uptake) |
| Pathology | Proposed cerebellar involvement (Purkinje cell loss, torpedoes — controversial); IPMDS 2018 consensus notes ET pathology unresolved; no consistent pathologic signature | Substantia nigra α-synuclein Lewy bodies |
Treatment
First-Line Pharmacotherapy
- Propranolol: 60–320 mg/d (start 10–20 mg BID, titrate); long-acting preferred; ~50% tremor amplitude reduction; Level A evidence
- Primidone: 12.5–25 mg qhs starting dose; target 250–750 mg/d; first-dose phenomenon (nausea, sedation, ataxia); Level A
- Propranolol and primidone are equally effective and can be combined
- Propranolol contraindicated in asthma, decompensated HF, severe bradycardia
Second-Line & Adjuncts
- Topiramate: 50–400 mg/d (typical effective 200–400 mg); Level B evidence; weight loss, cognitive side effects
- Gabapentin: 1200–3600 mg/d; Level B; useful as add-on
- Alprazolam: 0.75–2.75 mg/d; Level B; risk of dependence — use cautiously
- Clonazepam: useful adjunct, especially for orthostatic/task-specific tremor
- Botulinum toxin: Level B for hand tremor; Level C for head/voice; dose-dependent weakness
Surgical Options
- DBS of VIM (ventral intermediate) thalamus: gold standard for medication-refractory ET; ~70–90% tremor reduction
- MRI-guided focused ultrasound (MRgFUS): VIM thalamotomy; non-invasive; FDA-approved for ET (unilateral 2016; STAGED BILATERAL approved 2022 with interval between sides)
- Gamma Knife thalamotomy: VIM target; delayed onset of benefit (weeks–months); unilateral
- Bilateral thalamotomy/lesioning carries risk of dysarthria — bilateral DBS preferred when needed
💎 Board Pearl
- ET responds to alcohol; PD tremor does not — classic differentiator on boards
- Head tremor is common in ET, rare in PD — head tremor at rest suggests dystonic tremor, not PD
- DBS target for ET = VIM thalamus; DBS target for PD = STN or GPi
- Start primidone at 25 mg qhs — first-dose phenomenon can cause severe sedation/ataxia
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