What is the initial workup and treatment for a patient presenting with tremor?

Initial Workup and Treatment for Tremor

Start with propranolol 80-240 mg/day or primidone as first-line treatment if the tremor interferes with daily function or quality of life, after excluding medication-induced causes and metabolic disturbances through targeted history and basic laboratory evaluation. 1, 2

Initial Diagnostic Workup

History - Key Elements to Assess

Activation Pattern:

• Determine if tremor occurs at rest (suggests Parkinson's disease) or with action (suggests essential tremor or enhanced physiologic tremor) 3, 4
• Action tremors subdivide into postural (holding arms outstretched), kinetic (during movement), or intention (worsening near target) 3

Exacerbating Factors:

• Anxiety, caffeine, strenuous exercise, or fatigue suggest enhanced physiologic tremor rather than pathologic tremor 2
• Recent medication changes are critical - screen specifically for antiparkinsonians, lithium, and sympathomimetics 2

Functional Impact:

• Document specific interference with writing, eating, drinking, and activities of daily living - this determines treatment threshold 2
• Essential tremor can cause greater functional impairment than Parkinson's disease in these activities 5

Associated Features:

• Bradykinesia, rigidity, or gait changes suggest Parkinson's disease 3
• Dysarthria and ataxic gait with "wing-beating" tremor suggest cerebellar/intentional tremor 5
• Abrupt onset with spontaneous remissions and changing characteristics suggest psychogenic tremor 3

Physical Examination - Specific Maneuvers

• Observe tremor at complete rest with hands in lap (parkinsonian tremor) 3
• Test postural tremor with arms extended against gravity 3
• Assess kinetic tremor during finger-to-nose testing 4
• Examine for bradykinesia, dystonia, or peripheral neuropathy signs 6
• Check if tremor changes or disappears with distraction (psychogenic) 3

Laboratory and Imaging

• Basic metabolic panel to exclude metabolic disturbances 6
• Thyroid function tests if enhanced physiologic tremor suspected 3
• Brain MRI if cerebellar signs present or to exclude focal basal ganglia lesions before surgical consideration 1
• Single-photon emission computed tomography (SPECT) only if diagnostic uncertainty between essential tremor and Parkinson's disease 3

Treatment Algorithm

When to Treat

Treat only when tremor interferes with function or quality of life - not based solely on tremor presence 1, 2

For stress-related disability only, use propranolol or benzodiazepines during those specific periods 7

First-Line Pharmacological Treatment

Propranolol 80-240 mg/day:

• Most established medication with over 40 years of use 1
• Effective in up to 70% of patients 1, 2
• Contraindications: Chronic obstructive pulmonary disease, bradycardia, or congestive heart failure 1, 2, 5
• Common adverse effects: fatigue, depression, nausea, dizziness, insomnia, cold extremities, bronchospasm 1
• Dual benefit if patient has concurrent hypertension 1, 5

Primidone (alternative first-line):

• Comparable efficacy to propranolol (up to 70% response) 1, 2
• Critical pitfall: Requires 2-3 month trial period before assessing benefit - do not discontinue prematurely 1, 2
• Anti-tremor effect occurs even with subtherapeutic phenobarbital levels 1
• Side effects: behavioral disturbances, irritability, sleep disturbances at higher doses 1
• Teratogenic risk: Counsel women of childbearing age about neural tube defects 1

Alternative Beta-Blockers (if propranolol not tolerated)

• Nadolol 40-320 mg daily 1
• Metoprolol 25-100 mg extended release daily or twice daily 1
• Atenolol (limited evidence, moderate effect) 1
• Timolol 20-30 mg/day 1

Second-Line Medications

If first-line agents fail or cause intolerable side effects:

• Combination of propranolol plus primidone 7
• Gabapentin (limited evidence for moderate efficacy) 1, 7
• Topiramate 7, 8
• Benzodiazepines like clonazepam for intermittent use 7

Surgical Options for Medication-Refractory Tremor

Consider surgery when medications fail due to lack of efficacy at maximum doses, dose-limiting side effects, or medical contraindications 1, 2

Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) Thalamotomy - Preferred for unilateral tremor:

• Sustained tremor improvement of 56% at 4 years 1, 5
• Lowest complication rate at 4.4% compared to radiofrequency thalamotomy (11.8%) and DBS (21.1%) 1, 2, 5
• Early adverse effects: gait disturbance (36%) and paresthesias (38%), decreasing to 9% and 14% by 1 year 1
• Contraindications: Cannot undergo MRI, skull density ratio <0.40, bilateral treatment needed, or previous contralateral thalamotomy 1, 2, 5

Deep Brain Stimulation (DBS) of Ventral Intermediate Nucleus (VIM):

• Preferred for bilateral tremor or patients with MRgFUS contraindications 1, 2
• Provides adjustable, reversible tremor control 1
• Higher complication rate (21.1%) but suitable for younger patients needing long-term adjustability 1
• Approximately 90% tremor control rate 7

Radiofrequency Thalamotomy:

• Available but carries higher complication risk (11.8%) than MRgFUS 1, 5
• Consider only if MRgFUS and DBS unavailable 1

Common Pitfalls to Avoid

• Do not stop primidone before 2-3 months - therapeutic benefit takes time to manifest 1, 2
• Screen for beta-blocker contraindications before prescribing - COPD, bradycardia, CHF are absolute contraindications 1, 2, 5
• Avoid prescribing aids/equipment in acute phase - may interrupt normal movement patterns and prevent recovery 1, 2
• Do not treat based on tremor presence alone - only treat when functional disability exists 1, 2
• Monitor for hyperpyrexia and confusion if abruptly reducing or discontinuing treatment 9

Non-Pharmacological Approaches

• Rhythm modification techniques: superimpose alternative rhythms on existing tremor, gradually slow movement to rest 1, 2
• Use unaffected limb to dictate new rhythm for unilateral tremor 1
• Employ gross rather than fine movements for activities like handwriting 1
• Avoid cocontraction or muscle tensing as long-term strategy 1