What are the laboratory tests for peripheral neuropathy (nerve damage)?

From the Guidelines

For evaluating neuropathy, I recommend a comprehensive laboratory workup including complete blood count (CBC), comprehensive metabolic panel (CMP), hemoglobin A1c, vitamin B12 level, folate level, thyroid function tests (TSH, free T4), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) as per the latest guidelines from the Diabetes Care journal 1.

Key Laboratory Tests

• Complete blood count (CBC)
• Comprehensive metabolic panel (CMP)
• Hemoglobin A1c
• Vitamin B12 level
• Folate level
• Thyroid function tests (TSH, free T4)
• Erythrocyte sedimentation rate (ESR)
• C-reactive protein (CRP) Additional specialized tests should include serum protein electrophoresis (SPEP) with immunofixation, vitamin B6 level, methylmalonic acid, homocysteine, and anti-nuclear antibody (ANA) testing.

Specialized Tests

• Serum protein electrophoresis (SPEP) with immunofixation
• Vitamin B6 level
• Methylmalonic acid
• Homocysteine
• Anti-nuclear antibody (ANA) testing For suspected inflammatory neuropathies, consider anti-ganglioside antibodies, anti-MAG antibodies, and anti-sulfatide antibodies. Heavy metal screening (lead, mercury, arsenic) may be warranted based on exposure history.

Inflammatory and Toxin-Related Tests

• Anti-ganglioside antibodies
• Anti-MAG antibodies
• Anti-sulfatide antibodies
• Heavy metal screening (lead, mercury, arsenic) These tests help identify common causes of neuropathy such as diabetes, vitamin deficiencies, thyroid dysfunction, inflammatory conditions, paraproteinemias, and toxin exposures. The results guide appropriate treatment by addressing the underlying cause rather than just managing symptoms. Testing should be tailored to the patient's clinical presentation, with more specialized tests added based on initial findings and specific symptoms such as autonomic involvement, rapid progression, or family history suggesting hereditary neuropathy.

Clinical Assessment

Annual assessment for diabetic peripheral neuropathy starting at diagnosis of type 2 diabetes and 5 years after the diagnosis of type 1 diabetes, including a careful history and assessment of either temperature or pinprick sensation (small fiber function) and vibration sensation using a 128-Hz tuning fork (for large-fiber function), and annual 10-g monofilament testing to identify feet at risk for ulceration and amputation 1.

From the Research

Laboratory Tests for Neuropathy

• Initial blood tests for neuropathy should include:
  • Complete blood count
  • Comprehensive metabolic profile
  • Measurement of erythrocyte sedimentation rate and fasting blood glucose
  • Vitamin B12 and thyroid-stimulating hormone levels 2, 3, 4
• Specialized tests should be ordered if clinically indicated, such as:
  • Serum protein electrophoresis with immunofixation 3
  • Electrodiagnostic studies, including nerve conduction studies and electromyography 2, 3
  • Nerve biopsy 2, 4
• Laboratory tests should be selected specifically according to the suspected type of neuropathy to avoid unnecessary tests and expenses 4

Diagnosis and Evaluation

• Diagnosis of peripheral neuropathy requires a comprehensive history, physical examination, and judicious laboratory testing 2, 3
• Early peripheral neuropathy may present as sensory alterations, including sensory loss, numbness, pain, or burning sensations in a "stocking and glove" distribution of the extremities 3
• Physical examination should include a comprehensive neurologic and musculoskeletal evaluation 3
• If the initial evaluation is inconclusive, referral to a neurologist for additional testing should be considered 3, 4

Treatment and Management

• Treatment of peripheral neuropathy focuses on managing the underlying etiology 3
• Several classes of medications, including gabapentinoids and antidepressants, can help alleviate neuropathic pain 3
• Correction of any nutritional deficiencies is also an important part of treatment 2