Laboratory Workup for Peripheral Neuropathy
The recommended laboratory workup for a patient presenting with neuropathy should include screening for reversible causes with diabetic screen, vitamin B12, folate, TSH, and HIV testing, followed by consideration of serum protein electrophoresis and autoimmune screening. 1, 2
Initial Laboratory Evaluation
- Fasting blood glucose and hemoglobin A1c to screen for diabetes mellitus, one of the most common causes of peripheral neuropathy 1, 2
- Vitamin B12 level to identify deficiency, especially important in patients taking metformin 1, 3
- Thyroid-stimulating hormone (TSH) to evaluate for hypothyroidism 1, 2
- Complete blood count (CBC) to assess for anemia or other hematologic abnormalities 3
- Comprehensive metabolic profile to evaluate liver and kidney function 3
- Erythrocyte sedimentation rate to screen for inflammatory conditions 3
Additional Testing Based on Clinical Presentation
- Serum protein electrophoresis and immunofixation to evaluate for monoclonal gammopathy 4
- HIV testing when clinically indicated 2, 3
- Hepatitis B and C screening when clinically indicated 2
- Consider vasculitic and autoimmune screening panels in appropriate clinical contexts 4
Specialized Testing for Specific Neuropathy Types
- Anti-myelin-associated glycoprotein (anti-MAG) antibodies for patients with sensory peripheral neuropathies 4, 2
- Anti-ganglioside antibodies for suspected Guillain-Barré syndrome or motor neuropathies (e.g., anti-GQ1b for Miller Fisher variant) 4, 2
- Anti-ganglioside M1 antibodies for patients with motor neuropathy 4
- Cryoglobulins and cold agglutinin titers when symptoms suggest these disorders 4
- 24-hour urine for total protein, creatinine clearance, urine protein electrophoresis, and urine immunofixation electrophoresis when appropriate 4
Diagnostic Procedures to Consider
- Electrodiagnostic studies (nerve conduction studies and electromyography) to differentiate between axonal and demyelinating neuropathies 1, 5
- MRI of spine with or without contrast if radiculopathy or compressive lesion is suspected 4, 1
- MRI of brain if cranial nerve involvement is present 4, 1
- Lumbar puncture with CSF analysis for suspected inflammatory neuropathies (CSF typically shows elevated protein in Guillain-Barré syndrome) 4, 5
- Nerve biopsy in select cases when diagnosis remains unclear despite extensive testing 3, 5
- Skin biopsy to assess intraepidermal nerve fiber density if small-fiber neuropathy is suspected 5
Common Pitfalls to Avoid
- Failing to screen for diabetes in all patients with peripheral neuropathy, as it is the most common cause 1, 6
- Overlooking non-diabetic causes of neuropathy in patients with diabetes 1
- Neglecting to test vitamin B12 levels in patients taking metformin 1, 7
- Forgetting to consider toxic exposures, including alcohol and chemotherapeutics 8
- Not evaluating for autonomic neuropathy symptoms, which can significantly impact morbidity and mortality 1, 2
Special Considerations
- For immune checkpoint inhibitor-related neuropathy, follow specific protocols including frequent neurologic evaluation and pulmonary function assessment 4
- For suspected Guillain-Barré syndrome, immediate hospitalization and specialized testing are required 4, 1
- For patients with Waldenström macroglobulinemia, additional testing for cryoglobulins and cold agglutinins should be performed 4
By following this structured approach to laboratory workup for neuropathy, clinicians can efficiently identify treatable causes and develop appropriate management strategies to improve patient outcomes.