Cerebrospinal fluid neurofilament light chain predicts disease activity after the first demyelinating event suggestive of multiple sclerosis

Background: The prediction of disease activity in patients with a first demyelinating event suggestive of multiple sclerosis (MS) is of high clinical relevance. Cerebrospinal fluid (CSF) neurofilament light chain (NfL) has shown to have prognostic value in MS patients. In this work, we measured CSF NfL in patients at the first demyelinating event in order to find a cut-off value able to discriminate patients who will have disease activity from those who will remain stable during the follow-up. Methods: We included CSF samples collected within 30 days after the onset of the first demyelinating event from 32 patients followed-up for 3.8 ± 2.5 years. CSF NfL was measured with a newly developed in-house enzyme linked immunosorbent assay (ELISA). Results: At the first demyelinating event, patients with subsequent disease activity had significantly higher baseline CSF NfL values compared to clinically and radiologically stable patients (median 812.5 pg/mL, range 205–2359 pg/mL vs 329.5 pg/mL, range 156–3492 pg/mL, p = 0.002). A CSF NfL cut-off value of 500 pg/mL significantly discriminated these two groups of patients with a 90% sensitivity and an 83.3% specificity. Conclusion: Our results confirm that CSF NfL is a prognostic marker in the very early phases of MS. The validation of a cut-off value of 500 pg/mL could provide clinicians with a dichotomous variable that can simplify the prognostic assessment of patients at the first demyelinating event.