Neurofilament Light Chain Levels in a Large Idiopathic Peripheral Neuropathy Cohort

Neurofilament light chain (Nf-L) has been identified as a biomarker of neurodegeneration in many neuromuscular conditions, including several subtypes of polyneuropathies. The purpose of this research was to investigate whether Nf-L is also a promising biomarker for idiopathic peripheral neuropathy (IPN), the second most common subtype of axonal polyneuropathy. Nf-L levels were quantified using an ultrasensitive digital immunoassay SiMoA in plasma samples from 294 subjects. Participant inclusion required a diagnosis of IPN confirmed by electrodiagnostic testing, intraepidermal nerve fiber density (IENFD), and/or neuromuscular examination. Laboratory testing recommended by the American Academy of Neurology for the evaluation of polyneuropathy was normal in all subjects. In our cohort, the majority of participants (78.1%, N = 228) had Nf-L levels in the age-adjusted normal range. Those with elevated Nf-L levels had higher scores on two different neuropathy severity scores and were more likely to have abnormal electrodiagnostic testing, including reduced action potential amplitude in peroneal motor and sural sensory nerves. No differences in blood Nf-L levels were observed in those participants with a short duration (≤ 1.5 years) versus long duration (≥ 5 years) of disease. Nf-L levels were also not correlated with the presence of neuropathic pain, nor the location of paresthesia. Nf-L expression had the strongest correlation with age. In this cohort with IPN, Nf-L levels correlated with disease severity as assessed by clinical examination and electrophysiology. However, given that Nf-L was in the normal range for the majority of subjects in our cohort, its use as a biomarker for clinical trials evaluating new treatments for IPN will be limited.