What is the best approach to diagnose and manage a patient presenting with tremor, considering their age, medical history, and current medications?

Approach to a Patient with Tremor

Begin by categorizing the tremor based on its activation pattern: rest tremor suggests Parkinson's disease, postural/action tremor suggests essential tremor or enhanced physiologic tremor, and intention tremor suggests cerebellar pathology. 1

Initial Clinical Assessment

Activation Pattern Classification

• Rest tremor: Occurs in a body part that is relaxed and completely supported against gravity, typically improving with voluntary movement—this is the hallmark of Parkinsonian tremor 1, 2
• Action tremor: Occurs with voluntary muscle contraction and subdivides into:
  • Postural tremor: Present when maintaining a position against gravity 2, 3
  • Kinetic tremor: Occurs during voluntary movement 2, 3
  • Intention tremor: Progressively worsens during goal-directed movements, characteristic of cerebellar pathology 1

Key Historical Features to Elicit

• Duration of symptoms: Essential tremor requires at least 3 years of bilateral action tremor for diagnosis 4
• Age of onset: Onset after age 20 years is a red flag requiring further workup 4
• Laterality: Parkinsonian tremor is typically unilateral or asymmetric, while essential tremor is bilateral 4, 2
• Frequency: Essential tremor is 4-8 Hz, while Parkinsonian tremor is typically 4-6 Hz 4, 2
• Distractibility: Tremor that stops with distraction suggests functional (psychogenic) tremor; persisting tremor indicates organic cause 1
• Exacerbating factors: Anxiety, caffeine, physical exertion, and emotional stress worsen physiologic and essential tremor 4, 2

Physical Examination Specifics

• Observe tremor quality: Parkinsonian tremor has a "pill-rolling" quality affecting hands and legs 1
• Test for bradykinesia and rigidity: Two of three major features (rest tremor, bradykinesia, rigidity) confirm Parkinson's disease 5
• Assess for cerebellar signs: Look for dysarthria, ataxic gait, and progressive worsening during finger-to-nose testing 1
• Check for dystonic postures: Dystonic tremor is associated with abnormal posturing 2, 3

Exclude Secondary Causes

Medication-Induced Tremor

• Culprit medications: Stimulants, antipsychotics, lithium, valproate, and SSRIs 1
• Action required: Review and discontinue offending agents when possible 2

Metabolic and Endocrine Causes

• Screen for: Hyperthyroidism, hypoglycemia, and hypercalcemia 1
• Laboratory workup: TSH, glucose, calcium levels in appropriate clinical context 2

Diagnostic Imaging Strategy

When to Order Imaging

• MRI brain: Not required for essential tremor diagnosis but useful to exclude structural lesions, atrophy, or vascular disease 4
• Avoid CT head: Limited soft-tissue characterization makes it inferior to MRI 4
• Ioflupane SPECT/CT: Use when clinical examination is equivocal to exclude Parkinsonian syndromes by demonstrating normal dopamine transporter uptake in the striatum 4, 1

Common pitfall: Normal MRI does not exclude Parkinson's disease, as it remains a clinical diagnosis 4

Specific Tremor Diagnoses

Essential Tremor

• Diagnostic criteria: Bilateral action tremor of arms and hands for at least 3 years, without isolated head/voice tremor or task-specific tremor 4
• Consciousness: Remains intact during episodes 4
• Treatment initiation: Only when tremor interferes with function or quality of life 6, 4

Parkinsonian Tremor

• Clinical features: Unilateral or asymmetric rest tremor that improves with voluntary movement, plus bradykinesia and/or rigidity 1, 5
• Associated features: Cognitive slowing, speech abnormalities, depression, dysautonomia, sleep disturbances 5
• Pathophysiology: Degeneration of dopaminergic neurons in the substantia nigra 1

Cerebellar Tremor

• Characteristics: Intention tremor that becomes progressively worse during goal-directed movements and does not stop with distraction 1
• Associated findings: Dysarthria and ataxic gait 1

Psychogenic (Functional) Tremor

• Red flags: Abrupt onset, spontaneous remission, changing tremor characteristics, extinction with distraction 2, 3

Management Algorithm

For Essential Tremor

First-line pharmacotherapy: Propranolol (80-240 mg/day) or primidone, effective in up to 70% of patients 6, 4

• Propranolol contraindications: Chronic obstructive pulmonary disease, bradycardia, congestive heart failure, asthma 6, 4
• Propranolol side effects: Lethargy, depression, dizziness, hypotension, exercise intolerance, sleep disorders, cold extremities, bronchospasm 6, 4
• Alternative beta-blockers: Nadolol (40-320 mg daily), metoprolol (25-100 mg), atenolol, or timolol (20-30 mg/day) if propranolol is not tolerated 6
• Primidone considerations: Clinical benefits may not appear for 2-3 months; counsel women of childbearing age about teratogenic risks (neural tube defects) 6

Second-line options: Gabapentin or carbamazepine if first-line agents fail 6, 7

Surgical Interventions for Refractory Essential Tremor

When to consider surgery: Medications fail due to lack of efficacy at maximum doses, dose-limiting side effects, medical contraindications, or occupational limitations 6

• For unilateral tremor or patients with medical comorbidities: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is preferred due to lower complication rate (4.4% vs. 11.8% for radiofrequency thalamotomy vs. 21.1% for DBS) 6, 4
• MRgFUS efficacy: Sustained tremor improvement of 56% at 4 years 6, 4
• MRgFUS contraindications: Bilateral treatment, contralateral to previous thalamotomy, skull density ratio <0.40, inability to undergo MRI 6, 4
• For bilateral tremor: Deep brain stimulation (DBS) is the procedure of choice, providing adequate tremor control in approximately 90% of patients with adjustable, reversible, and optimizable control 4, 7

For Parkinsonian Tremor

• Primary treatment: Dopaminergic therapy targeting the underlying Parkinson's disease 5
• Diagnostic confirmation: If clinical uncertainty persists, use ioflupane SPECT/CT to visualize dopaminergic pathway integrity 2, 3