What is the clinical and laboratory evaluation approach for a new onset tremor?

Clinical Evaluation of New Onset Tremor

The evaluation of a new onset tremor requires focused assessment of tremor characteristics, associated neurological signs, and targeted laboratory testing to determine the underlying cause, with serum glucose and sodium testing being the most important initial laboratory investigations.

Tremor Characterization

Activation Conditions

• Rest tremor: Occurs when body part is relaxed and supported against gravity

  • Most commonly seen in Parkinson's disease (typically asymmetric) 1
  • Also seen in drug-induced parkinsonism and some metabolic disorders

• Action tremor: Occurs with voluntary muscle contraction 1

  • Postural tremor: When maintaining position against gravity
  • Kinetic tremor: During voluntary movement
  • Intention tremor: Worsens as approaching target (cerebellar)
  • Isometric tremor: During muscle contraction against stationary object

Topographic Distribution

• Upper extremities: Most common location (essential tremor, Parkinson's disease)
• Head/neck: Common in essential tremor, dystonic tremor
• Voice: May indicate essential tremor or spasmodic dysphonia
• Lower extremities: Less common, may indicate orthostatic tremor or Parkinson's disease
• Asymmetric vs. symmetric: Asymmetry suggests Parkinson's disease 2

Frequency Assessment

• Low frequency (3-5 Hz): Typical of Parkinson's disease
• Medium frequency (5-8 Hz): Common in essential tremor
• High frequency (>8 Hz): Physiologic tremor, enhanced physiologic tremor 3

Key Historical Features to Assess

1. Onset and progression: Sudden vs. gradual onset
2. Exacerbating/alleviating factors: Stress, caffeine, alcohol response
3. Family history: Essential tremor often has autosomal dominant inheritance 1
4. Medication review: Beta-agonists, lithium, valproate, SSRIs, stimulants
5. Substance use: Alcohol, caffeine, illicit drugs
6. Associated symptoms: Bradykinesia, rigidity, balance problems
7. Functional impact: Impact on activities of daily living

Physical Examination

1. Tremor observation:

   • At rest
   • With arms outstretched (postural)
   • During finger-to-nose testing (kinetic/intention)
   • During writing or drawing spirals

2. Associated neurological signs:

   • Bradykinesia, rigidity, postural instability (Parkinson's)
   • Dystonic posturing (dystonic tremor)
   • Cerebellar signs (ataxia, dysmetria)
   • Neuropathic signs (sensory loss, weakness)

Laboratory Investigations

First-line Laboratory Tests

• Serum glucose: Hypoglycemia can cause tremor 4, 5
• Serum sodium: Hyponatremia can cause tremor 4, 5
• Thyroid function tests: Hyperthyroidism commonly causes enhanced physiologic tremor
• Liver function tests: Hepatic encephalopathy can present with asterixis/tremor

Second-line Laboratory Tests (Based on Clinical Suspicion)

• Toxicology screen: When substance use is suspected 5
• Serum ceruloplasmin/copper: For Wilson's disease (in younger patients)
• Ethanol level: For alcohol-related tremor or withdrawal 5
• Acetaminophen level: If overdose is suspected 5
• Calcium, magnesium, phosphate: Not routinely recommended unless specific clinical indications 4

Imaging Studies

• Brain CT or MRI: Not routinely recommended for all tremor patients 4
  • Indicated for:
    • Sudden onset tremor
    • Asymmetric or unilateral tremor
    • Associated focal neurological deficits
    • Red flags (headache, altered mental status)
    • Tremor with atypical features

Special Considerations

Red Flags Requiring Urgent Evaluation

• Acute or subacute onset with rapid progression
• Associated headache, altered mental status
• Focal neurological deficits
• History of malignancy
• Fever or signs of infection

Common Pitfalls

1. Misdiagnosing essential tremor as Parkinson's disease: Essential tremor is an action tremor, while Parkinson's tremor is primarily a rest tremor
2. Missing drug-induced tremors: Always review all medications
3. Overlooking psychogenic tremor: Features include abrupt onset, spontaneous remissions, changing characteristics, and extinction with distraction 1
4. Failing to consider metabolic causes: Especially in acute onset tremors

Follow-up Recommendations

• Refer to a neurologist when:
  • Diagnosis is uncertain
  • Tremor is severe or disabling
  • First-line treatments are ineffective
  • Atypical features are present

Conclusion

A systematic approach to tremor evaluation involves careful characterization of tremor phenomenology, focused history and examination, and targeted laboratory testing. While most tremors are benign, proper evaluation is essential to identify treatable causes and guide appropriate management.