What is the recommended lab workup for a patient presenting with neuropathy?

Laboratory Workup for Peripheral Neuropathy

The recommended laboratory workup for a patient presenting with neuropathy should include blood glucose, serum B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein immunofixation electrophoresis as these tests provide the highest yield of abnormality. 1

Initial Screening Tests

• Blood glucose (fasting blood glucose and/or hemoglobin A1c) to screen for diabetes mellitus, the most common cause of peripheral neuropathy 1, 2
• Serum B12 with metabolites (methylmalonic acid with or without homocysteine) to identify vitamin B12 deficiency, particularly important in patients taking metformin 1, 2
• Serum protein immunofixation electrophoresis to evaluate for monoclonal gammopathy 1, 2
• Thyroid-stimulating hormone (TSH) to assess for hypothyroidism 2, 3
• Complete blood count to evaluate for anemia or other hematologic abnormalities 3
• Comprehensive metabolic panel to assess renal and liver function 3
• Erythrocyte sedimentation rate to screen for inflammatory conditions 3

Additional Testing Based on Clinical Presentation

• If there is no definite evidence of diabetes mellitus by routine testing of blood glucose, testing for impaired glucose tolerance should be considered in distal symmetric sensory polyneuropathy 1
• HIV testing when clinically indicated 2
• Hepatitis B and C screening when clinically indicated 2
• Vasculitic and autoimmune screening panels in appropriate clinical contexts 2

Specialized Testing for Specific Neuropathy Types

• Anti-myelin-associated glycoprotein (anti-MAG) antibodies for patients with sensory peripheral neuropathies 1, 2
• Anti-ganglioside M1 antibodies for patients with motor neuropathy 1, 2
• Cryoglobulins and cold agglutinin titers when symptoms suggest these disorders 1
• 24-hour urine for total protein, creatinine clearance, urine protein electrophoresis, and urine immunofixation electrophoresis when appropriate 1

Diagnostic Procedures to Consider

• Electrodiagnostic studies (nerve conduction studies and electromyography) to differentiate between axonal and demyelinating neuropathies 4
• Neurological testing including temperature sensation, pinprick sensation, vibration perception, pressure sensation, and ankle reflexes for screening of distal symmetric polyneuropathy 1
• For primary care settings or epidemiologic surveys, 128-Hz tuning fork (for large fiber function) and 10-g monofilament testing are recommended to identify risk of foot ulcers and amputations 1
• Skin biopsy with intraepidermal nerve fiber density measurement for diagnosing small fiber neuropathy 4

Genetic Testing Considerations

• Genetic testing is established as useful for accurate diagnosis and classification of hereditary neuropathies 1
• Genetic testing may be considered in patients with cryptogenic polyneuropathy who exhibit a hereditary neuropathy phenotype 1
• Initial genetic testing should be guided by clinical phenotype, inheritance pattern, and electrodiagnostic features, focusing on the most common abnormalities (CMT1A duplication/HNPP deletion, Cx32, and MFN2 mutation screening) 1

Common Pitfalls to Avoid

• Failing to screen for diabetes in all patients with peripheral neuropathy, as it is the most common cause 2
• Overlooking non-diabetic causes of neuropathy in patients with diabetes 2
• Neglecting to test vitamin B12 levels in patients taking metformin 2
• Not evaluating for autonomic neuropathy symptoms, which can significantly impact morbidity and mortality 2
• Relying solely on serum viscosity results for intervention decisions in patients with Waldenström macroglobulinemia, as there can be long turnaround times and potential technical issues 1

Special Considerations

• For immune checkpoint inhibitor-related neuropathy, specific protocols including frequent neurologic evaluation should be followed 1
• For suspected Guillain-Barré syndrome, lumbar puncture with cerebrospinal fluid analysis may be helpful 5
• For patients with Waldenström macroglobulinemia and peripheral neuropathy, evaluation for antibodies against myelin-associated glycoprotein (MAG) or other glycoproteins should be considered 1