What are the characteristic features and treatment options for essential tremors?

Essential Tremor: Characteristic Features and Treatment

Clinical Features

Essential tremor is a progressive neurological syndrome characterized primarily by bilateral action tremor of the arms and hands, with a frequency of 4-8 Hz, that significantly interferes with quality of life and can cause greater functional impairment than Parkinson's disease in activities like writing, eating, drinking, and reading. 1, 2

Key Diagnostic Characteristics

• Bilateral action tremor affecting the arms and hands is the hallmark presentation 1
• Tremor frequency ranges between 4-8 Hz 2
• Consciousness remains intact during tremor episodes 2
• Tremor worsens with emotional stress, caffeine consumption, and physical exertion 2
• Symptoms are progressive over time 1, 3

Diagnostic Criteria

• Bilateral action tremor present for at least 3 years is necessary for diagnosis 3
• Absence of isolated head and voice tremor 3
• Absence of task- and position-dependent tremor 3

Red Flags Suggesting Alternative Diagnosis

• Duration of attacks greater than 1 minute 2
• Age of onset over 20 years 2
• Abnormalities in brain CT/MRI scanning 2

Conditions That Must Be Excluded

• Cerebrovascular disease 2
• Demyelinating disease 2
• Metabolic disorders 2
• Brain trauma 2
• Psychological disorders 2

Severity Classification

• Mild: minimal interference with daily activities 2
• Moderate: some interference with daily activities 2
• Severe: significant interference with daily activities 2

Treatment Algorithm

When to Initiate Treatment

Treatment should only be initiated when tremor symptoms interfere with function or quality of life. 4, 1

First-Line Pharmacological Treatment

Propranolol (80-240 mg/day) or primidone are recommended as first-line treatments, effective in up to 70% of patients. 4, 1

Propranolol

• Dosage: 80-240 mg/day 4, 1
• Most established medication with over 40 years of demonstrated efficacy 4
• Avoid in patients with COPD, bradycardia, or congestive heart failure 4, 1
• Common adverse effects include fatigue, depression, nausea, dizziness, insomnia, cold extremities, and bronchospasm 4
• May provide dual benefits for patients with both essential tremor and hypertension 4, 1
• In elderly patients, excessive heart rate reduction may lead to serious adverse events 4

Primidone

• First-line option alongside propranolol 4
• Therapeutic benefit can occur even when derived phenobarbital levels remain subtherapeutic, confirming primidone itself has anti-tremor properties 4
• Clinical benefits may not become apparent for 2-3 months, so an adequate trial period is essential 4
• Side effects include behavioral disturbances, irritability, and sleep disturbances, particularly at higher doses 4
• Women of childbearing age should be counseled about teratogenic risks (neural tube defects) 4

Alternative Beta-Blockers

• Nadolol: 40-320 mg daily 4
• Metoprolol: 25-100 mg extended release daily or twice daily 4
• Atenolol: limited evidence for moderate effect 4
• Timolol: 20-30 mg/day 4

Second-Line Medications

• Carbamazepine may be used as second-line therapy, though generally not as effective as first-line therapies 4
• Gabapentin has limited evidence for moderate efficacy 4
• Topiramate may be helpful 5, 6
• Benzodiazepines (such as clonazepam) can provide benefit if primidone and propranolol do not provide adequate control 7

Combination Therapy

If either primidone or propranolol alone do not provide adequate control, the medications can be used in combination. 7

Monitoring and Dose Adjustments

• Regular assessment of tremor severity and medication side effects is essential 4
• Dose adjustments may be needed based on clinical response and tolerability 4
• If first-line agents fail, consider switching to or adding second-line medications before considering surgical options 4

Surgical Interventions for Refractory Tremor

Indications for Surgery

Surgical therapies should be considered when medications fail due to lack of efficacy at maximum doses, dose-limiting side effects, medical contraindications, or occupational limitations. 4, 5

Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) Thalamotomy

MRgFUS thalamotomy is the preferred surgical option for unilateral tremor or patients with medical comorbidities, showing sustained tremor improvement of 56% at 4 years with the lowest complication rate (4.4%) compared to radiofrequency thalamotomy (11.8%) and DBS (21.1%). 4, 1

Efficacy and Safety Profile

• Sustained tremor improvement of 56% at 4 years 4, 1
• Lowest complication rate at 4.4% compared to other surgical options 4, 1
• Early adverse effects include gait disturbance (36%) and paresthesias (38%), which decrease to 9% and 14% respectively by 1 year 4
• 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 4

Contraindications

• Cannot undergo MRI 4, 1
• Skull density ratio <0.40 4, 1
• Bilateral treatment 4, 1
• Contralateral to a previous thalamotomy 4, 1

Deep Brain Stimulation (DBS)

DBS is preferred for patients with bilateral tremor involvement or those with contraindications to MRgFUS, offering adjustable and reversible tremor control. 4, 5

Patient Selection

• Relatively young patients benefit from adjustable treatment option 4
• Bilateral tremor involvement (MRgFUS not indicated bilaterally) 4
• Patients should have no dementia or severe depression 4
• Sufficient residual motor function to expect improvement following surgery 4
• No cerebral atrophy or focal lesions of the basal ganglia on MRI 4

Surgical Details

• Ventral intermediate nucleus (VIM) of the thalamus is the established target 4
• Left-sided stimulation is appropriate for unilateral treatment targeting dominant hand tremor 4
• Awake procedure allows for intraoperative testing to confirm optimal electrode placement and immediate tremor control 4
• Typically requires inpatient admission for careful monitoring in the immediate post-operative period 4
• Complication rate of 21.1%, higher than MRgFUS but offers adjustability 4, 1

Radiofrequency Thalamotomy

• Available but carries higher complication risks (11.8%) compared to MRgFUS 4, 1
• Only considered when DBS or focused ultrasound is not possible 5

Non-Pharmacological Approaches

Rhythm Modification Techniques

• Superimposing alternative rhythms on existing tremor and gradually slowing movement to complete rest 4
• For unilateral tremor, using the unaffected limb to dictate a new rhythm can help entrain the tremor to stillness 4
• Using gross rather than fine movements can be helpful, especially for activities like handwriting 4
• Avoid cocontraction or tensing of muscles as this is unlikely to be a helpful long-term strategy 4

Important Pitfalls to Avoid

• Avoid prescribing aids and equipment for functional tremor in the acute phase, as they may interrupt normal automatic movement patterns 4
• If aids are necessary for safety, they should be considered short-term solutions with a plan to progress toward independence 4