Initial Laboratory Workup for Peripheral Neuropathy
The initial laboratory workup for diagnosing peripheral neuropathy should include complete blood count, comprehensive metabolic panel, fasting blood glucose, HbA1c, vitamin B12, TSH, and erythrocyte sedimentation rate to identify the most common treatable causes. 1
Initial Diagnostic Approach
Step 1: Clinical Assessment
- Perform comprehensive foot examination including:
- 10-g monofilament testing (primary test)
- At least one additional test: pinprick sensation, temperature sensation, vibration testing using 128-Hz tuning fork, or ankle reflex assessment 2
- One or more abnormal tests suggests loss of protective sensation (LOPS)
- At least two normal tests (and no abnormal test) rules out LOPS 2
Step 2: Basic Laboratory Tests
- Complete blood count
- Comprehensive metabolic panel
- Fasting blood glucose and HbA1c
- Vitamin B12 level
- Thyroid-stimulating hormone (TSH) level
- Erythrocyte sedimentation rate (ESR) 1, 3
- Serum protein electrophoresis with immunofixation 3
Step 3: Additional Testing Based on Clinical Suspicion
- For suspected nutritional deficiencies:
- Folate level
- Vitamin B6 level 2
- For suspected inflammatory conditions:
- C-reactive protein (CRP)
- Antinuclear antibody (ANA) 2
- For suspected vasculitis:
- Anti-neutrophil cytoplasmic antibodies (ANCA) 2
- For suspected immune-mediated neuropathies:
- Anti-MAG antibodies
- Ganglioside antibodies (anti-GM1, anti-GQ1b)
- SSA/SSB antibodies 2
- For suspected heavy metal toxicity:
- Heavy metal screening (lead, mercury, arsenic) 1
- For suspected infectious causes:
- Hepatitis B or C panel
- HIV testing
- Lyme disease serology 1
Special Considerations
When to Consider Electrodiagnostic Studies
- When clinical features are atypical
- When diagnosis remains unclear after initial testing
- To differentiate between axonal and demyelinating neuropathy
- To assess severity and distribution of nerve involvement 2, 3
When to Consider Referral to Neurology
- Severe or rapidly progressive symptoms
- Asymmetric presentation
- Significant motor involvement
- Autonomic symptoms
- When initial workup is inconclusive 3, 4
Important Caveats
- Diabetes is the most common cause of peripheral neuropathy, affecting up to 50% of patients with diabetes, with many cases being asymptomatic 1
- In patients with severe or atypical neuropathy, causes other than diabetes should always be considered, including neurotoxic medications, heavy metal poisoning, alcohol abuse, renal disease, and inflammatory neuropathies 2
- Up to 25-46% of peripheral neuropathy cases remain idiopathic despite comprehensive evaluation 3
- Early identification of treatable causes is critical to prevent progression and improve quality of life 1
- Specialized testing should be guided by clinical presentation rather than performed as a screening battery for all patients 5
Remember that peripheral neuropathy often presents with sensory alterations in a "stocking and glove" distribution that may progress to include proximal numbness, distal weakness, or atrophy if left untreated 3.