Peripheral Neuropathy: A Review.
Level 5 - mechanism / opinion, no new human data
Narrative clinical review without systematic search methodology or meta-analytic pooling
PubMed 41247746 · doi:10.1001/jama.2025.19400
What was done
This narrative clinical review summarized the epidemiology, causes, clinical presentation, initial diagnostic evaluation, and medical management of peripheral neuropathy in adults based on published literature.
What was found
Peripheral neuropathy affects approximately 1% of adults globally, with diabetes causing more than 50% of cases in Western populations and affecting roughly 206 million individuals worldwide. Up to 27% of adult neuropathy cases have no identifiable etiology after diagnostic workup. Recommended initial diagnostic testing includes blood glucose, serum vitamin B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein electrophoresis with immunofixation. First-line pharmacologic agents for neuropathic pain include alpha-2-delta calcium channel subunit ligands (gabapentin, pregabalin), SNRIs (duloxetine, venlafaxine), and tricyclic antidepressants (amitriptyline, nortriptyline). In patients with painful diabetic peripheral neuropathy, 38% receiving 1200 mg daily of gabapentin achieved at least a 50% reduction in pain. Complete reversal of nerve damage is uncommon.
Why it matters
This review outlines an evidence-based approach to diagnosing and managing peripheral neuropathy across hundreds of potential causes, setting clear diagnostic testing priorities and realistic efficacy expectations for neuropathic pain relief.
Limits
As a narrative review, the synthesis does not follow formal systematic review or meta-analytic screening protocols. The abstract provides quantitative response rates for only one drug and dose (gabapentin 1200 mg) and does not report effect sizes, sample sizes, or comparative efficacy metrics for alternative first-line agents or non-pharmacologic interventions.
Cited by
- supports Diabetes is the leading cause of peripheral neuropathy in the United States.