Serum Neurofilament Light in Neurosyphilis: A Pilot Study

Background Lumbar puncture is recommended for individuals with syphilis who have neurological symptoms; however, symptoms have poor sensitivity for predicting symptomatic neurosyphilis. Neurofilament light chain (NfL) is a marker for neuroaxonal injury; cerebrospinal fluid concentrations are higher in symptomatic neurosyphilis than in uncomplicated syphilis or asymptomatic neurosyphilis. Methods Serum NfL was quantified in 20 individuals with uncomplicated syphilis, 10 with asymptomatic neurosyphilis and 10 with symptomatic neurosyphilis using an ultrasensitive single-molecule array assay; it was repeated a median of 12.5 months after neurosyphilis therapy. Serum NfL concentration was age-adjusted using a published formula. Results Age-adjusted serum NfL concentration was significantly higher in symptomatic neurosyphilis compared with each of the other 2 groups. It was above the highest value in uncomplicated syphilis in 1 of 10 participants with asymptomatic neurosyphilis and 3 of 10 with symptomatic neurosyphilis. Serum NfL concentration increased in 1 participant with asymptomatic neurosyphilis with possible treatment failure. Conclusions If confirmed in a larger study, serum NfL may be a useful adjunct for identifying central nervous system infection by Treponema pallidum .