Laboratory Workup for Peripheral Neuropathy

Initial Screening Tests

The American Academy of Physical Medicine and Rehabilitation recommends blood glucose (fasting blood glucose and/or hemoglobin A1c) to screen for diabetes mellitus, the most common cause of peripheral neuropathy 1
Serum B12 with metabolites (methylmalonic acid with or without homocysteine) is recommended to identify vitamin B12 deficiency, particularly important in patients taking metformin 1
Serum protein immunofixation electrophoresis is used to evaluate for monoclonal gammopathy 1

Testing for impaired glucose tolerance should be considered in distal symmetric sensory polyneuropathy if there is no definite evidence of diabetes mellitus by routine testing of blood glucose 1
HIV testing is recommended when clinically indicated 2
Hepatitis B and C screening is recommended when clinically indicated 2

Anti-myelin-associated glycoprotein (anti-MAG) antibodies are recommended for patients with sensory peripheral neuropathies 3
Anti-ganglioside M1 antibodies are recommended for patients with motor neuropathy 3
Cryoglobulins and cold agglutinin titers are recommended when symptoms suggest these disorders 3

Electrodiagnostic studies (nerve conduction studies and electromyography) are recommended to differentiate between axonal and demyelinating neuropathies 4
Neurological testing including temperature sensation, pinprick sensation, vibration perception, pressure sensation, and ankle reflexes is recommended for screening of distal symmetric polyneuropathy 5
The American Diabetes Association recommends 128-Hz tuning fork (for large fiber function) and 10-g monofilament testing to identify risk of foot ulcers and amputations 5, 6

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

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

For immune checkpoint inhibitor-related neuropathy, specific protocols including frequent neurologic evaluation should be followed 7
For patients with Waldenström macroglobulinemia and peripheral neuropathy, evaluation for antibodies against myelin-associated glycoprotein (MAG) or other glycoproteins should be considered 3