What is the approach to diagnosing and treating tremors?

Approach to Tremors

Begin by categorizing the tremor based on its activation condition (rest vs. action), topographic distribution, and frequency—this classification immediately narrows the differential diagnosis and guides subsequent evaluation. 1, 2

Initial Clinical Characterization

Activation Pattern Assessment

• Rest tremor (4-6 Hz): Occurs when the body part is completely relaxed and supported against gravity; strongly suggests Parkinsonian tremor 3, 1
• Action tremor: Occurs with voluntary muscle contraction and subdivides into:
  • Postural tremor: Present when maintaining a position against gravity (e.g., arms outstretched) 1, 2
  • Kinetic tremor: Occurs during voluntary movement 1, 2
  • Intention tremor: Coarse, irregular tremor that worsens during goal-directed movements with "wing-beating" appearance on finger-to-nose testing; indicates cerebellar pathology 4

Critical History Elements

• Onset and progression: Abrupt onset with spontaneous remission suggests psychogenic tremor 1, 2
• Topographic distribution: Document which body parts are affected (hands, head, voice, legs) 3
• Frequency and amplitude: High-frequency, low-amplitude suggests physiologic tremor; lower frequency suggests pathologic causes 1, 2
• Factors that worsen tremor: Anxiety, caffeine, fatigue, medications enhance physiologic tremor 5, 1
• Factors that improve tremor: Alcohol improves essential tremor in 50-70% of cases; distraction eliminates psychogenic tremor 1, 2
• Family history: Essential tremor has autosomal dominant inheritance in 50% of cases 1, 2

Differential Diagnosis by Tremor Type

Rest Tremor

Parkinsonian tremor is the most common cause of rest tremor and requires immediate evaluation for Parkinson disease. 1, 6

• Key features: Typically asymmetric, 4-6 Hz, "pill-rolling" quality, improves with voluntary movement 3, 1
• Associated findings to assess:
  • Bradykinesia (slowness of movement) 3
  • Rigidity (cogwheel or lead-pipe) 3
  • Postural instability 3
  • Shuffling gait, festination, or freezing 3
  • Reduced arm swing 7
  • Masked facies, hypophonia, micrographia 7

Red flags for atypical parkinsonism (MSA, PSP, CBD): Early prominent falls, rapid progression, poor levodopa response, early autonomic dysfunction, vertical gaze palsy 3

Action Tremor

Essential Tremor (Most Common Pathologic Tremor)

• Prevalence: Affects 0.4-6% of population 1, 2
• Characteristics: Bilateral postural and kinetic tremor of hands/arms, may involve head (yes-yes or no-no), voice, or legs 8
• Diagnostic criteria: Bilateral action tremor for ≥3 years, absence of isolated head/voice tremor, absence of task-specific tremor 8
• Distinguishing features: No other neurologic signs, improves with alcohol in many cases, progressive over years 8

Enhanced Physiologic Tremor

• Triggers: Anxiety, stress, caffeine, fatigue, strenuous exercise, medications (beta-agonists, valproate, lithium, SSRIs) 5, 1
• Characteristics: High-frequency (8-12 Hz), low-amplitude, bilateral postural tremor 1, 6
• Management: Address underlying triggers; propranolol 80-240 mg/day is first-line if pharmacotherapy needed 5

Cerebellar (Intention) Tremor

• Characteristics: Coarse, irregular, worsens during goal-directed movements, "wing-beating" appearance 4
• Associated findings: Dysarthria, ataxic gait, dysmetria, dysdiadochokinesia 4
• Etiologies: Multiple sclerosis, stroke, traumatic brain injury, Wilson disease, medications, toxins 4

Critical "Cannot Miss" Diagnoses in Young Patients

Wilson Disease

In any patient under age 40 with tremor, Wilson disease must be excluded—it is treatable and fatal if missed. 3

• Clinical features: Tremor (often wing-beating), dystonia, parkinsonian features, drooling, oropharyngeal dystonia, psychiatric symptoms 3
• Screening tests: Serum ceruloplasmin, 24-hour urinary copper, slit-lamp examination for Kayser-Fleischer rings 3

Drug-Induced Tremor

• Common culprits: Valproate, lithium, SSRIs, beta-agonists, corticosteroids, antiemetics (metoclopramide), amiodarone 1, 6
• Caffeine: Extremely common cause in young patients that is often overlooked 3
• Antipsychotics: Can cause akathisia (severe restlessness with pacing), not true tremor 3

Psychogenic Tremor

• Diagnostic features: Abrupt onset, spontaneous remission, changing characteristics, extinction with distraction, highly variable frequency 3, 1
• Important: This is NOT a diagnosis of exclusion; positive clinical signs must be demonstrated 6

Diagnostic Workup Algorithm

Step 1: Focused Neurological Examination

• Assess tremor activation: Rest vs. postural vs. kinetic vs. intention 3, 1
• Evaluate for parkinsonism: Bradykinesia, rigidity, postural instability, gait abnormalities 3, 7
• Cerebellar testing: Finger-to-nose, heel-to-shin, rapid alternating movements, gait 4
• Dystonia assessment: Abnormal postures, task-specificity 6

Step 2: Laboratory Evaluation

• All patients with unexplained tremor:

  • Thyroid function tests (hyperthyroidism causes enhanced physiologic tremor) 1, 6
  • Comprehensive metabolic panel (hepatic/renal dysfunction) 1
  • Complete blood count 1

• Young patients (<40 years) or atypical features:

  • Serum ceruloplasmin and 24-hour urinary copper (Wilson disease) 3
  • Slit-lamp examination for Kayser-Fleischer rings 3

Step 3: Neuroimaging

• MRI brain without contrast: Optimal imaging modality for structural causes, parkinsonian syndromes, cerebellar pathology, Wilson disease 9, 3
• When to order: Atypical features, young age, rapid progression, associated neurologic signs, intention tremor 9, 3

Step 4: Specialized Testing (When Diagnostic Uncertainty Exists)

• Ioflupane (DaTscan) SPECT: Differentiates parkinsonian syndromes (PD, MSA, PSP, CBD) from essential tremor and drug-induced tremor 9

  • Normal scan: Essentially excludes parkinsonian syndromes 9
  • Abnormal scan: Shows decreased dopamine transporter uptake in striatum 9

• Levodopa trial: Robust response supports Parkinson disease; poor response suggests atypical parkinsonism 3

Treatment Approach by Tremor Type

Essential Tremor

• First-line pharmacotherapy: Propranolol 80-240 mg/day (avoid in COPD, bradycardia, CHF) 5, 8
• Alternative beta-blockers: Nadolol, metoprolol, atenolol 5
• Second-line: Primidone (start low, titrate slowly due to side effects) 8
• Refractory cases: Deep brain stimulation of ventral intermediate nucleus of thalamus 5, 8
• Head/voice tremor: Botulinum toxin injections 6, 8

Parkinsonian Tremor

• Levodopa/carbidopa: First-line for Parkinson disease 3
• Dopamine agonists: Alternative or adjunctive therapy 10
• Refractory tremor: Deep brain stimulation of subthalamic nucleus or globus pallidus interna 8

Enhanced Physiologic Tremor

• Non-pharmacologic: Avoid caffeine, reduce stress, avoid strenuous exercise before precision tasks 5
• Pharmacologic: Propranolol 80-240 mg/day if lifestyle modifications insufficient 5

Cerebellar Tremor

• Limited pharmacologic options: Propranolol, clonazepam may provide modest benefit 6
• Weighted utensils and adaptive devices: Help with functional tasks 6
• Severe cases: Deep brain stimulation may be considered 6

Common Pitfalls to Avoid

• Do not assume all tremors in young patients are benign essential tremor—Wilson disease must be excluded 3
• Do not overlook medication-induced tremor—review all medications, supplements, and caffeine intake 3, 1
• Do not confuse akathisia (restlessness from antipsychotics) with tremor—akathisia manifests as pacing and inability to sit still 3
• Do not use beta-blockers in elderly patients without careful consideration—risk of excessive heart rate reduction and serious adverse events 5
• Do not diagnose psychogenic tremor as exclusion—positive clinical signs (variability, distractibility, entrainment) must be demonstrated 6
• Do not miss serotonin syndrome in patients on multiple serotonergic medications—look for tremor with hyperreflexia, clonus, autonomic instability 9