How should essential tremor be diagnosed and managed in an adult patient?

Essential Tremor: Diagnosis and Management

First-Line Pharmacological Treatment

Start propranolol (80-240 mg/day) or primidone as first-line therapy for essential tremor—both achieve meaningful tremor reduction in approximately 70% of patients and are the most established treatments with over 40 years of demonstrated efficacy. 1

Propranolol Considerations

• Propranolol is the most established medication for essential tremor and should be the initial choice for most patients 1
• Contraindications include: chronic obstructive pulmonary disease, asthma, bradycardia (<50 bpm), decompensated heart failure, second- or third-degree heart block, and sick sinus syndrome without pacemaker 1, 2, 3
• Common adverse effects include fatigue, depression, nausea, dizziness, insomnia, cold extremities, bronchospasm, lethargy, hypotension, and exercise intolerance 1
• In elderly patients, excessive heart rate reduction may lead to serious adverse events 1
• Dual benefit: For patients with both essential tremor and hypertension, propranolol provides treatment for both conditions 1, 2

Primidone Considerations

• Primidone is an equally effective first-line alternative to propranolol 1
• The anti-tremor effect comes from primidone itself, not just its metabolite phenobarbital—therapeutic benefit can occur even when phenobarbital levels remain subtherapeutic 1
• Clinical benefits may not become apparent for 2-3 months, so an adequate trial period is essential 1
• Side effects include behavioral disturbances, irritability, and sleep disturbances, particularly at higher doses 1
• Women of childbearing age must be counseled about teratogenic risks, specifically neural tube defects 1
• Use a "start low, go slow" approach to minimize side effects 1

When to Initiate Treatment

• Medications should only be initiated when tremor symptoms interfere with function or quality of life 1, 2
• For tremor that is disabling only during periods of stress and anxiety, propranolol or benzodiazepines can be used intermittently during those specific periods 4, 5

Second-Line and Combination Therapy

• If propranolol or primidone alone provide inadequate control, combine both medications before moving to other options 4
• Alternative beta-blockers (metoprolol 25-100 mg extended release daily or twice daily, atenolol, nadolol 40-320 mg daily, or timolol 20-30 mg/day) may be tried if propranolol causes intolerable side effects 1, 4, 6
• Gabapentin has limited evidence for moderate efficacy as a second-line option 1, 6
• Topiramate may be considered as an alternative antiepileptic drug 6
• Benzodiazepines (such as clonazepam) can provide benefit, particularly in patients with associated anxiety 4, 6, 5

Diagnostic Criteria and Differential Diagnosis

Essential Tremor Diagnosis

• Bilateral action/postural tremor of the upper limbs with frequency of 4-8 Hz that worsens during voluntary movement and with stress 3
• Must be present for ≥3 years 3
• Absence of bradykinesia or rigidity on examination 3
• Absence of isolated head and voice tremor and absence of task- and position-dependent tremor 7

Key Differentiating Features from Parkinson's Disease

• Bradykinesia on examination is the key discriminating sign indicating a parkinsonian disorder rather than essential tremor 3
• Parkinsonian tremor is an asymmetric resting tremor (4-6 Hz) that diminishes with movement and is accompanied by rigidity (cogwheel or lead-pipe) and bradykinesia 3
• Essential tremor is bilateral and worsens with action, while Parkinsonian tremor is asymmetric and present at rest 3
• DaTscan (Ioflupane SPECT/CT) showing normal dopamine-transporter uptake effectively excludes Parkinsonian syndromes when clinical findings are equivocal 3

Red Flags Requiring Further Investigation

• Age of onset >20 years warrants additional investigation to exclude secondary causes 3
• Abnormal brain CT/MRI requires further work-up to rule out structural lesions 3

Surgical Options for Medication-Refractory Tremor

Indications for Surgery

• Consider surgical therapies when medications fail due to lack of efficacy at maximum doses, dose-limiting side effects, medical contraindications, or occupational limitations 1, 2

Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) Thalamotomy

• MRgFUS thalamotomy shows sustained tremor improvement of 56% at 4 years with the lowest complication rate (4.4%) compared to radiofrequency thalamotomy (11.8%) and deep brain stimulation (21.1%) 1, 2, 3
• Early adverse effects include gait disturbance (36%) and paresthesias (38%), which decrease to 9% and 14% respectively by 1 year 1
• Serious adverse events are rare (1.6%), with most adverse events being mild or moderate (98.4%) and more than 50% resolving by 1 year 1
• Preferred for unilateral tremor or patients with medical comorbidities due to lower complication rates 1
• Contraindications: Cannot undergo MRI, skull density ratio <0.40, bilateral treatment needed, or previous contralateral thalamotomy 1, 2

Deep Brain Stimulation (DBS)

• Bilateral DBS yields tremor control in approximately 90% of refractory cases 3, 4
• Preferred for bilateral tremor involvement since MRgFUS is not indicated for bilateral treatment 1
• Provides adjustable, reversible tremor control that can be optimized over time 1
• The ventral intermediate nucleus (VIM) of the thalamus is the established target 1
• Higher complication rate (21.1%) compared to MRgFUS but offers reversibility and adjustability 1, 2

Radiofrequency Thalamotomy

• Available but carries higher complication risks (11.8%) than MRgFUS 1, 2
• Generally not preferred given superior alternatives 1

Monitoring and Dose Adjustments

• Regular assessment of tremor severity and medication side effects is essential 1
• Dose adjustments should be made based on clinical response and tolerability 1
• If first-line agents fail, switch to or add second-line medications before considering surgical options 1