Causes of Tremors
Tremors arise from a broad spectrum of etiologies that can be systematically categorized into primary tremor disorders, secondary causes (including drugs and toxins), neurodegenerative conditions, and rare syndromes.
Primary Tremor Disorders
Essential tremor represents the most common primary tremor disorder, typically presenting as bilateral action tremor (postural and kinetic) affecting the hands, though it can involve the head, voice, and other body parts 1. This is a clinical diagnosis made when other causes are excluded.
Enhanced physiologic tremor occurs in everyone but becomes clinically apparent under certain conditions (anxiety, fatigue, hyperthyroidism, caffeine) 1.
Drug-Induced Tremor
Drug-induced tremor is one of the most common and reversible causes of tremor that must be actively sought in every patient 2. The most frequently implicated medications include:
- Psychiatric medications: SSRIs/SNRIs, tricyclic antidepressants (amitriptyline), lithium 2, 3
- Cardiac drugs: Amiodarone, β-adrenoceptor agonists 2
- Anticonvulsants: Valproate 2
- Dopaminergic agents: Dopamine receptor antagonists, VMAT2 inhibitors 2
- Substances of abuse: Ethanol, cocaine, caffeine 2, 3
Risk factors for drug-induced tremor include polypharmacy, male gender, older age, high doses, and immediate-release preparations 2. Most drug-induced tremors resolve after discontinuation of the offending agent, though tardive tremor can persist 2.
Parkinsonian Syndromes
Parkinson disease is the most common disorder causing resting tremor 1. The tremor is typically asymmetric, pill-rolling in character, and improves with voluntary movement. Other Parkinsonian syndromes include:
- Multiple system atrophy (MSA)
- Progressive supranuclear palsy (PSP)
- Corticobasal degeneration (CBD)
I-123 ioflupane SPECT/CT is valuable for differentiating Parkinsonian syndromes from essential tremor and drug-induced tremor, with a normal scan essentially excluding Parkinsonian syndromes 4. MRI brain without contrast is the optimal anatomic imaging modality for evaluating Parkinsonian syndromes 4.
Dystonic Tremor
Dystonic tremor occurs in patients with dystonia and is typically irregular, position-specific, and may have a null point where the tremor disappears 1. Features suggesting dystonic tremor include unilateral presentation, task-specificity, and position-dependency 2.
Cerebellar Tremor
Cerebellar tremor manifests as intention tremor (worsening during goal-directed movement) and is associated with other cerebellar signs like ataxia, dysmetria, and dysdiadochokinesia 1.
Neurotoxic Exposures
Occupational and environmental exposures to heavy metals and chemicals can cause tremor 5:
- Mercury: Can cause intention tremor and other neurological symptoms
- Lead: Produces tremor as part of acute toxicity syndrome
- Organic solvents: Chronic exposure causes postural and action tremor
- Pesticides: Various tremor types depending on the agent
Diagnosis requires detailed occupational history and may need industrial hygiene assessment 5.
Rare and Unusual Tremor Syndromes
Several uncommon entities should be considered when typical diagnoses don't fit 6:
- Fragile X-associated tremor/ataxia syndrome (FXTAS): Intention tremor with ataxia in older males
- Wilson's disease: Wing-beating tremor with Kayser-Fleischer rings and liver disease
- Orthostatic tremor: High-frequency leg tremor (13-18 Hz) occurring only when standing
- Primary writing tremor: Task-specific tremor during writing
- Peripheral trauma-induced tremor: Follows limb injury
- Myorhythmia: Slow (1-4 Hz), rhythmic movement often involving cranial muscles
Functional (Psychogenic) Tremor
Features suggesting functional tremor include sudden onset, distractibility, entrainment with contralateral movements, and arrest with contralateral ballistic movements 2. This diagnosis requires positive signs, not just exclusion of organic causes.
Clinical Approach Pitfalls
A common pitfall is overdiagnosing essential tremor when faced with any action tremor 6. The evaluation must distinguish between action tremor (postural, kinetic, intention) versus resting tremor as the first critical step, as this fundamentally narrows the differential diagnosis 1.
Another critical error is failing to obtain a comprehensive medication and substance use history, missing easily reversible drug-induced causes 2, 3. Always inquire about over-the-counter medications, supplements, caffeine intake, and recreational drug use.