What is the recommended assessment and treatment approach for patients presenting with tremors?

Tremor Assessment and Management

For patients presenting with tremor, begin by categorizing the tremor based on its activation condition (rest vs. action), topographic distribution, and frequency, then initiate treatment with propranolol (80-240 mg/day) or primidone as first-line therapy when tremor interferes with function or quality of life. 1, 2

Initial Clinical Assessment

Key History Elements

• Activation condition: Determine if tremor occurs at rest (body part relaxed and supported against gravity) or with action (voluntary muscle contraction) 3, 4
• Temporal characteristics: Document duration of attacks, age of onset (red flag if >20 years), and progression pattern 1
• Frequency range: Essential tremor typically presents at 4-8 Hz 1
• Exacerbating factors: Assess worsening with emotional stress, caffeine consumption, physical exertion, anxiety, medication use, or fatigue 1, 3
• Functional impact: Evaluate interference with writing, eating, drinking, reading, and other daily activities 5
• Family history: Essential tremor has autosomal dominant transmission in 50% of cases 3, 4
• Medication review: Screen for drugs causing tremor (lithium, calcium channel blockers, antiparkinsonians) and those causing xerostomia (anxiolytics, antidepressants, antimuscarinics) 6
• Precipitating conditions: Identify anemia, infection, inflammation, fever, thyroid disorders, or metabolic disturbances 6

Physical Examination Findings

• Tremor characteristics: Observe for bilateral action tremor of arms/hands (essential tremor) vs. asymmetric resting tremor (Parkinson's disease) 5, 3
• Neurologic signs: Examine for bradykinesia, rigidity, dystonia, ataxic gait, dysarthria, or peripheral neuropathy 7, 8
• Systemic findings: Check for pallor, sweating, or tremor suggesting anemia or thyrotoxicosis 6
• Alternative diagnoses: Assess blood pressure differences between limbs, irregular pulse, heart murmurs, friction rub, or pain on palpation 6
• Gait and speech: Evaluate for cerebellar signs (ataxia, dysarthria) or parkinsonian features 1

Diagnostic Classification

Action Tremor (Most Common)

Postural/kinetic tremor occurring with voluntary movement:

• Essential tremor: Bilateral upper limb action tremor, progressive, may respond to alcohol, no other neurologic signs 1, 5
• Enhanced physiologic tremor: Temporary, related to specific triggers (anxiety, caffeine, fatigue), low-amplitude, high-frequency 3, 4
• Dystonic tremor: Associated with dystonic posturing, irregular, task-specific 9, 10
• Cerebellar tremor: Intention tremor with goal-directed movements, coarse and irregular, "wing-beating" appearance, accompanied by ataxia and dysarthria 5

Resting Tremor

Tremor in relaxed, gravity-supported body part:

• Parkinsonian tremor: Asymmetric, 4-6 Hz, decreases with voluntary movement, associated with rigidity and bradykinesia 7, 3, 4
• Drug-induced: Consider dopamine antagonists, lithium, valproate 8, 10

Red Flags Requiring Further Investigation

• Duration of attacks >1 minute 1
• Age of onset >20 years 1
• Abnormalities on brain CT/MRI 1
• Abrupt onset with spontaneous remission (psychogenic tremor) 3, 4
• Focal neurologic deficits suggesting stroke, demyelination, or structural lesion 1

Initial Investigations

• Laboratory tests: Thyroid function, electrolytes, renal function, calcium, HbA1c to exclude metabolic/endocrine disorders 6
• Brain MRI: If atypical features, focal deficits, or age of onset >20 years to exclude cerebrovascular disease, demyelinating disease, or structural lesions 1
• SPECT imaging: Consider if diagnostic uncertainty between essential tremor and Parkinson's disease to visualize dopaminergic pathway integrity 3, 4

Treatment Algorithm

First-Line Pharmacotherapy (Essential Tremor)

Initiate treatment only when tremor interferes with function or quality of life 1, 2, 5:

• Propranolol: 80-240 mg/day, most established medication with >40 years of use, effective in up to 70% of patients 2, 5

  • Contraindications: Chronic obstructive pulmonary disease, bradycardia, congestive heart failure 2, 5
  • Adverse effects: Fatigue, depression, nausea, dizziness, insomnia, cold extremities, bronchospasm, exercise intolerance 2
  • Dual benefit: Consider in patients with both essential tremor and hypertension 2, 5

• Primidone: Alternative first-line option, effective in up to 70% of patients 2

  • Dosing considerations: Therapeutic benefit may occur even with subtherapeutic phenobarbital levels; clinical benefits may take 2-3 months 2
  • Adverse effects: Behavioral disturbances, irritability, sleep disturbances at higher doses 2
  • Precautions: Counsel women of childbearing age about teratogenic risks (neural tube defects) 2

Second-Line Medications

If first-line agents fail due to lack of efficacy, side effects, or contraindications 2:

• Alternative beta-blockers: Nadolol (40-320 mg/day), metoprolol (25-100 mg ER daily or BID), timolol (20-30 mg/day) 2
• Gabapentin: Limited evidence for moderate efficacy 2
• Carbamazepine: May be used as second-line therapy, though generally less effective than first-line options 2

Surgical Interventions for Refractory Tremor

Consider when medications fail due to lack of efficacy at maximum doses, dose-limiting side effects, medical contraindications, or occupational limitations 2:

Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) Thalamotomy

• Efficacy: Sustained tremor improvement of 56% at 4 years 2, 5
• Complication rate: 4.4% (lower than radiofrequency thalamotomy at 11.8% and DBS at 21.1%) 2, 5
• Adverse effects: Gait disturbance (36%), paresthesias (38%) initially, decreasing to 9% and 14% by 1 year; serious adverse events rare (1.6%) 2
• Contraindications: Cannot undergo MRI, skull density ratio <0.40, bilateral treatment needed, previous contralateral thalamotomy 2, 5
• Preferred for: Unilateral tremor or patients with medical comorbidities 2

Deep Brain Stimulation (DBS)

• Target: Ventral intermediate nucleus (VIM) of thalamus 2
• Advantages: Adjustable, reversible tremor control that can be optimized over time 2
• Preferred for: Relatively young patients, bilateral tremor involvement, patients with contraindications to MRgFUS 2
• Eligibility criteria: No dementia or severe depression, sufficient residual motor function, no cerebral atrophy or focal basal ganglia lesions on MRI 2
• Complication rate: 21.1% 2, 5

Radiofrequency Thalamotomy

• Complication rate: 11.8% (higher than MRgFUS) 2, 5
• Consider: When MRgFUS unavailable or contraindicated and DBS not preferred 2

Non-Pharmacological Approaches

• Rhythm modification techniques: Superimpose alternative rhythms on existing tremor, gradually slow movement to complete rest 2
• Unilateral tremor: Use unaffected limb to dictate new rhythm to entrain tremor to stillness 2
• Movement strategies: Use gross rather than fine movements (especially for handwriting), avoid cocontraction or muscle tensing 2
• Avoid: Prescribing aids/equipment in acute phase as they may interrupt normal automatic movement patterns; if necessary for safety, consider short-term with plan toward independence 2

Monitoring and Follow-Up

• Regular assessment: Evaluate tremor severity and medication side effects at each visit 2
• Dose adjustments: Titrate based on clinical response and tolerability 2
• Treatment escalation: If first-line agents fail, switch to or add second-line medications before considering surgical options 2
• Adequate trial period: Allow 2-3 months for primidone to demonstrate full clinical benefit 2

Common Pitfalls to Avoid

• Misdiagnosis: Essential tremor is commonly misdiagnosed; carefully examine for bradykinesia, dystonia, or peripheral neuropathy suggesting alternative etiologies 8
• Overlooking drug-induced tremor: Always review medications in patients with recent-onset tremor 8
• Premature equipment prescription: Avoid aids in acute phase of functional tremor as they interrupt normal movement patterns 2
• Inadequate beta-blocker screening: Always assess for COPD, bradycardia, or heart failure before prescribing propranolol 2, 5
• Insufficient trial duration: Allow adequate time (2-3 months) for medications like primidone to demonstrate efficacy 2