Laboratory Workup for Peripheral Neuropathy

Initial Laboratory Evaluation

The American College of Physicians recommends 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 should be checked to identify deficiency, especially important in patients taking metformin 1
Thyroid-stimulating hormone (TSH) should be evaluated to assess for hypothyroidism 1, 2

Serum protein electrophoresis and immunofixation should be performed to evaluate for monoclonal gammopathy 3, 4
HIV testing should be considered when clinically indicated 2
Hepatitis B and C screening should be performed when clinically indicated 2
Vasculitic and autoimmune screening panels should be considered in appropriate clinical contexts 3, 4

Anti-myelin-associated glycoprotein (anti-MAG) antibodies should be tested for patients with sensory peripheral neuropathies 5, 2
Anti-ganglioside antibodies should be tested for suspected Guillain-Barré syndrome or motor neuropathies 6, 2
Anti-ganglioside M1 antibodies should be tested for patients with motor neuropathy 5
Cryoglobulins and cold agglutinin titers should be evaluated when symptoms suggest these disorders 5
24-hour urine for total protein, creatinine clearance, urine protein electrophoresis, and urine immunofixation electrophoresis should be performed when appropriate 5

Electrodiagnostic studies (nerve conduction studies and electromyography) should be performed to differentiate between axonal and demyelinating neuropathies 1
MRI of spine with or without contrast should be considered if radiculopathy or compressive lesion is suspected 3, 1
MRI of brain should be considered if cranial nerve involvement is present 3, 1
Lumbar puncture with CSF analysis should be performed for suspected inflammatory neuropathies 6

Failing to screen for diabetes in all patients with peripheral neuropathy, as it is the most common cause 1
Overlooking non-diabetic causes of neuropathy in patients with diabetes 1
Neglecting to test vitamin B12 levels in patients taking metformin 1
Not evaluating for autonomic neuropathy symptoms, which can significantly impact morbidity and mortality 1, 2

For immune checkpoint inhibitor-related neuropathy, specific protocols including frequent neurologic evaluation and pulmonary function assessment should be followed 7, 6
For suspected Guillain-Barré syndrome, immediate hospitalization and specialized testing are required 6, 1
For patients with Waldenström macroglobulinemia, additional testing for cryoglobulins and cold agglutinins should be performed 5