Clinical Utility of Serum Neurofilament Light Chain in Peripheral Neuropathy

The clinical utility of serum neurofilament light chain (sNfL) in the evaluation and management of peripheral neuropathy (PN) remains poorly defined. This study aimed to evaluate the utility of sNfL for diagnosing PN, assessing disease activity, and monitoring treatment response using a commercially available assay.

This was a retrospective cohort study at the University of Pennsylvania between June 2024 and March 2025. Patients with, or at risk for, PN who underwent sNfL testing were included. Demographics, PN etiology, clinical findings, and sNfL levels were analyzed.

One hundred and twenty-eight patients were included: 41 with chronic inflammatory demyelinating polyneuropathy (CIDP), 36 with transthyretin amyloidosis (ATTR), 13 with vasculitic PN, 13 with Charcot-Marie-Tooth disease (CMT), 6 with multifocal motor neuropathy (MMN), 4 with anti-MAG neuropathy, 4 with Guillain-Barré syndrome (GBS), and 11 with other PN types. Of these, 113 had definite large fiber PN; 14 were asymptomatic TTRv carriers, and one had small fiber neuropathy. Elevated sNfL levels were observed in 31 patients (24%). The odds ratio of having elevated sNfL in treatable vs. non-treatable PN was 28.33 (95% CI: 5.04-159.18). Among CIDP and ATTRv-PN patients, sNfL was most often elevated in treatment-naïve or refractory cases and decreased with treatment.

Routine sNfL testing is warranted in selected patients with PN, such as treatment-naïve or refractory CIDP, active vasculitic PN, and ATTRv-PN. Elevated sNfL in patients with PN should prompt evaluation for a potentially treatable cause and may offer useful adjunctive information to support clinical decision-making.