What are the possible differential diagnoses for tremor?

Differential Diagnosis of Tremor

The most common tremors in primary care are enhanced physiologic tremor, essential tremor, and parkinsonian tremor, and the key to diagnosis is categorizing tremor by activation condition (rest vs. action), topographic distribution, and frequency. 1

Initial Classification Framework

Begin by determining the activation condition of the tremor, which immediately narrows the differential:

Resting Tremor (occurs when body part is relaxed and supported against gravity)

• Parkinson disease – Most common pathologic resting tremor, typically unilateral at onset, becomes less prominent with voluntary movement, and is present in >70% of PD patients as the presenting feature 1
• Drug-induced parkinsonism – Antipsychotics and dopamine antagonists can produce resting tremor with lead pipe rigidity 2
• Monosymptomatic resting tremor – A special subgroup of Parkinson disease presenting with isolated resting tremor 3

Action Tremor (occurs with voluntary muscle contraction)

Postural tremor (maintaining position against gravity):

• Enhanced physiologic tremor – Low-amplitude, high-frequency tremor present in all persons but amplified by anxiety, caffeine, medications (beta-agonists, valproate, lithium, SSRIs), hyperthyroidism, or fatigue 1, 4
• Essential tremor – The most common pathologic tremor affecting 0.4-6% of the population, bilateral upper limb action tremor, autosomal dominant in 50% of cases 1, 5
• Dystonic tremor – Tremor occurring in a body part affected by dystonia, often irregular and position-specific 4
• Orthostatic tremor – Rare syndrome of high-frequency tremor (13-18 Hz) in legs when standing, relieved by sitting or walking 3, 4

Kinetic tremor (during voluntary movement):

• Essential tremor – Can manifest as both postural and kinetic tremor, often with intention component 1, 5
• Cerebellar tremor – Intention tremor that worsens as target is approached, associated with other cerebellar signs (dysmetria, dysdiadochokinesia, ataxia) 2, 4
• Holmes' tremor – Low-frequency tremor (<4.5 Hz) with both resting and intention components, typically from midbrain lesions 3

Critical Distinguishing Features

Parkinson Disease vs. Essential Tremor

This is the most common diagnostic challenge in elderly patients with tremor 6:

Parkinson disease characteristics:

• Unilateral onset, resting tremor that decreases with action 1, 6
• Accompanied by bradykinesia and rigidity (not isolated tremor) 6
• Micrographic handwriting that is small but not tremulous 6
• Pill-rolling quality (thumb-finger tremor) 1

Essential tremor characteristics:

• Bilateral upper limb action tremor from onset 1, 6
• Tremor is the only neurologic sign present 6
• Handwriting is tremulous but normal-sized 6
• Often improves with alcohol consumption 1, 5
• May involve head (titubation) or voice, which is rare in PD 5

Drug-Induced Tremor

Always review medications in any patient with new-onset tremor 4, 5:

• Antipsychotics – Can cause both parkinsonian resting tremor and neuroleptic malignant syndrome with tremor, rigidity, and autonomic instability 2
• Serotonergic agents – Tremor is a key feature of serotonin syndrome, accompanied by hyperreflexia, clonus, and autonomic hyperactivity 7
• Beta-agonists, valproate, lithium, amiodarone – Enhance physiologic tremor 1, 4

Rare but Important Tremor Syndromes

• Psychogenic tremor – Abrupt onset, spontaneous remission, changing characteristics, extinction with distraction 1
• Palatal tremor – Can be essential (no structural lesion) or symptomatic (brainstem/cerebellar lesion) 3
• Primary orthostatic tremor – High-frequency leg tremor when standing, relieved by sitting 3, 4

Metabolic and Toxic Causes

• Hyperthyroidism – Enhances physiologic tremor 1, 4
• Hypoglycemia – Can produce action tremor 4
• Alcohol withdrawal – Coarse action tremor 4
• Heavy metal toxicity – Mercury, lead can cause tremor 4

Diagnostic Approach Algorithm

1. Determine activation condition: Rest vs. action (postural/kinetic/intention)
2. Assess distribution: Unilateral vs. bilateral, body parts involved
3. Measure frequency: High (>8 Hz) vs. low (<4 Hz)
4. Search for associated signs: Bradykinesia, rigidity, dystonia, ataxia, neuropathy
5. Review medication list: Recent additions or dose changes
6. Check for metabolic causes: Thyroid function, glucose, electrolytes
7. Consider imaging: Single-photon emission computed tomography (SPECT) or transcranial ultrasonography if diagnostic uncertainty between PD and ET 1

Common Pitfalls

• Misdiagnosing essential tremor with intention component as cerebellar tremor – Essential tremor patients with intention tremor lack other cerebellar signs 3
• Missing drug-induced tremor – Always review medications, including over-the-counter stimulants and supplements 4, 5
• Overlooking serotonin syndrome – Tremor with hyperreflexia and clonus in patients on serotonergic agents requires immediate recognition 7
• Confusing neuroleptic malignant syndrome with other causes – Lead pipe rigidity with tremor and fever in antipsychotic users is NMS until proven otherwise 2, 8