A new study reports that obtaining neurofilament-light chain levels in patients with a first demyelinating event is useful to identify those at risk of developing multiple sclerosis (Cornabella et al. Neurol Neuroimmunol Neuroinflamm 2025;12:e200370).

The retrospective study analysed data for 181 patients (mean age 35 years) presenting with clinically isolated syndrome (CIS) over an 18-year period. Patients were assessed for dissemination in space (DIS), defined as >1 typical MS lesion in >2 topographies; and dissemination in time (DIT), defined as >1 gadolinium-enhancing lesions coexisting with non-enhancing lesions. MS was diagnosed when there was new disease activity, defined as >1 relapses and/or >1 MRI lesion. The study objective was to determine the prognostic value of sNfL in patients with DIS but not DIT (OCB-positive vs. OCB-negative) and no DIS or DIT. At the start of the study, 51.9% met DIS/DIT criteria, 34.3% had DIS/noDIT, and 13.8% had noDIS/noDIT. A total of 79% were OCB-positive.

sNfL was obtained a median of 1.5 months after CIS diagnosis. sNfL z-scores and EBNA1-specific IgG levels were significantly higher in patients who were OCB-positive. Baseline sNfL z-scores were significantly elevated in CIS patients with DIS + DIT compared to the DIS/noDIT and noDIS/noDIT groups.

Baseline sNfL levels were also significantly higher in the 40% of noDIS/noDIT patients who were subsequently diagnosed with MS after a median of eight years. An sNfL z-score of 1.64 was identified as the cutoff for differentiating patients with vs. without disease activity during follow-up (positive predictive value 87.5%, negative predictive value 82.4%). A cutoff z-score of 1.64 had a PPV of 100% for the subgroup of patients presenting with optic neuritis, the most common presenting symptom.

In the subgroup of OCB-negative patients, serum glial fibrillary acidic protein (GFAP) was more useful than sNfL in differentiating patients who subsequently had disease activity; the optimal cutoff value was 68.69 pg/mL (PPV 83.3%, NPV 100%). However, the combination of GFAP level >68.69 pg/mL and sNfL z-score >1.28 increased the PPV to 100%.

The authors noted that all patients with elevated sNfL and GFAP at baseline subsequently developed disease activity, underscoring the usefulness of both of these measures in the early evaluation of patients. They further noted that sNfL is a reasonable, less invasive alternative to OCBs.