What tests should be ordered to diagnose neuropathy?

Diagnostic Testing for Neuropathy

For diagnosing neuropathy, order a comprehensive assessment that includes clinical examination, electrodiagnostic studies, and laboratory tests to identify the etiology and determine appropriate management. 1, 2

Clinical Neurological Examination

• Assess for distal symmetric polyneuropathy using temperature sensation, pinprick sensation, vibration perception (using 128-Hz tuning fork), pressure sensation (using 10-g monofilament), and ankle reflexes 1
• Evaluate for small-fiber function through temperature and pinprick sensation testing 1
• Test large-fiber function using vibration perception, 10-g monofilament testing, and ankle reflex assessment 1
• Document any autonomic symptoms including orthostatic dizziness, syncope, dry cracked skin, resting tachycardia, or peripheral dryness 1

Laboratory Tests

• Order fasting blood glucose and/or hemoglobin A1c to screen for diabetes mellitus, the most common cause of neuropathy 2
• Include serum B12 with metabolites (methylmalonic acid with or without homocysteine), particularly important in patients taking metformin 2
• Request serum protein immunofixation electrophoresis to evaluate for monoclonal gammopathy 2
• Consider glucose tolerance test if routine glucose testing is normal but distal symmetric sensory polyneuropathy is present 2
• Order HIV, hepatitis B and C screening when clinically indicated 2

Specialized Testing

• Order electrodiagnostic studies (nerve conduction studies and electromyography) to differentiate between axonal and demyelinating neuropathies 2, 3
• Consider anti-myelin-associated glycoprotein (anti-MAG) antibodies for patients with sensory peripheral neuropathies 2
• Request anti-ganglioside M1 antibodies for patients with motor neuropathy 2
• Order cryoglobulins and cold agglutinin titers when symptoms suggest these disorders 2
• Consider skin biopsy for intraepidermal nerve fiber density assessment if small-fiber neuropathy is suspected 4, 5

Autonomic Testing

• For suspected autonomic neuropathy, order heart rate variability testing, postural hypotension testing, and ambulatory blood pressure monitoring 1
• Consider quantitative sudomotor axon reflex test (QSART) to detect distal sudomotor loss with high sensitivity (75-90%) 1
• For gastrointestinal neuropathies, consider scintigraphy and electrogastrography 1
• For bladder dysfunction, order ultrasound to determine bladder volume and residual urine volume 1

Special Considerations

• Genetic testing should be considered in patients with cryptogenic polyneuropathy who exhibit a hereditary neuropathy phenotype 2
• For immune checkpoint inhibitor-related neuropathy, include frequent neurologic evaluation 2
• For patients with Waldenström macroglobulinemia and peripheral neuropathy, evaluate for antibodies against myelin-associated glycoprotein (MAG) 2

Common Pitfalls to Avoid

• Do not fail to screen for diabetes in all patients with peripheral neuropathy, as it is the most common cause 2
• Do not overlook non-diabetic causes of neuropathy in patients with diabetes 2
• Avoid neglecting to test vitamin B12 levels in patients taking metformin 2
• Remember that electrophysiological testing or referral to a neurologist is rarely needed, except when clinical features are atypical or diagnosis is unclear 1