What is the initial workup for peripheral neuropathy?

Initial Workup for Peripheral Neuropathy

The initial workup for peripheral neuropathy should include a comprehensive neurological assessment with 10-g monofilament testing plus at least one other neurological assessment tool (pinprick, temperature perception, vibration with 128-Hz tuning fork, or ankle reflexes), followed by targeted laboratory testing including complete blood count, comprehensive metabolic profile, fasting blood glucose, HbA1c, vitamin B12, and thyroid-stimulating hormone levels. 1, 2

Clinical Assessment

History

• Onset and progression of symptoms (acute vs. chronic)
• Distribution pattern (stocking-glove, asymmetric, proximal)
• Symptom characteristics (pain, numbness, weakness)
• Medical history (diabetes, alcohol use, toxic exposures)
• Medication history (chemotherapy, other neurotoxic drugs)
• Family history of neuropathy

Physical Examination

• Small-fiber function assessment:

  • Pinprick sensation
  • Temperature sensation

• Large-fiber function assessment:

  • Vibration perception using 128-Hz tuning fork
  • 10-g monofilament testing (critical for identifying loss of protective sensation)

• Additional neurological assessment:

  • Muscle strength
  • Deep tendon reflexes
  • Proprioception
  • Assessment for foot deformities
  • Skin integrity examination

Laboratory Testing

First-line Laboratory Tests

1. Complete blood count (CBC)
2. Comprehensive metabolic profile
3. Fasting blood glucose and HbA1c
4. Vitamin B12 level
5. Thyroid-stimulating hormone (TSH)
6. Erythrocyte sedimentation rate (ESR)
7. Serum protein electrophoresis with immunofixation 2, 3

Second-line Laboratory Tests (Based on Clinical Suspicion)

• Hepatitis panel
• HIV testing
• Lyme disease serology
• Vitamin B6 level
• Folate level
• Antinuclear antibody (ANA)
• Rheumatoid factor
• Anti-ganglioside antibodies (if GBS suspected)
• Heavy metal screening
• Genetic testing (if hereditary neuropathy suspected) 2, 3, 4

Electrodiagnostic Studies

• Nerve conduction studies (NCS) and electromyography (EMG) should be considered when:
  • Initial laboratory workup is inconclusive
  • Atypical presentation or rapid progression
  • Need to differentiate between axonal and demyelinating neuropathy
  • Need to determine severity and distribution 3, 5

Additional Testing Based on Specific Scenarios

• Lumbar puncture and CSF analysis: Consider for suspected Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy 1
• Skin biopsy: For evaluation of small fiber neuropathy when other tests are normal 5
• Nerve biopsy: Reserved for select cases when diagnosis remains unclear despite extensive testing 5

Important Considerations

• Peripheral neuropathy is idiopathic in 25-46% of cases 3
• Diabetic neuropathy is a diagnosis of exclusion - other causes should be ruled out even in patients with diabetes 1
• Up to 50% of diabetic peripheral neuropathy may be asymptomatic but still places patients at risk for insensate injury 2
• Early identification of treatable causes is critical for preventing progression and improving outcomes

Common Pitfalls to Avoid

• Attributing neuropathy to diabetes without excluding other causes
• Focusing only on symptomatic treatment without identifying underlying etiology
• Delaying electrodiagnostic studies when the diagnosis is unclear
• Overlooking potentially reversible causes such as vitamin deficiencies, hypothyroidism, or toxic exposures
• Failing to perform regular screening in high-risk patients (e.g., those with diabetes)

By following this systematic approach to peripheral neuropathy workup, clinicians can efficiently identify the underlying cause and implement appropriate treatment strategies to improve patient outcomes.