Prognostic value of serum neurofilaments in patients with clinically isolated syndromes

Abstract

Objective: To assess the prognostic role of serum neurofilament light chains (NfL) for clinically defined multiple sclerosis (CDMS) and McDonald 2017 multiple sclerosis (MS) in patients with clinically isolated syndromes (CIS).

Methods: We retrospectively analyzed data of patients admitted to our neurologic department between 2000 and 2015 for a first demyelinating event. We evaluated baseline serum NfL in addition to CSF, MRI, and clinical data.

Results: Among 222 patients who were enrolled (mean follow-up 100.6 months), 45 patients (20%) developed CDMS and 141 patients (63.5%) developed 2017 MS at 2 years. Serum NfL (median 22.0, interquartile range 11.6-40.4 pg/mL) was noticeably increased in patients with a recent relapse, with a high number of T2 and gadolinium-enhancing lesions at baseline MRI. Serum NfL was prognostic for both CDMS and McDonald 2017 MS, with a threefold and a twofold respective reduction in CDMS and 2017 MS risk in those patients with low and extremely low levels of NfL. The results remained unchanged subsequent to adjustment for such established MS prognostic factors as oligoclonal bands, Gd-enhancing lesions, and a high T2 lesion load at baseline MRI. NfL was associated with disability at baseline but not at follow-up.

Conclusions: Serum NfL have a prognostic value for CIS patient conversion to MS. NfL might play a twin role as biomarker in MS as peak level measurements can act as a quantitative marker of serious inflammatory activity, while steady-state levels can be a reflection of neurodegenerative and chronic inflammatory processes.

Figure 1. Baseline predictors of serum neurofilament levels

Figure 2. Smoothed plot of hazard ratios

Smoothed plot of hazard ratios for clinically definite multiple sclerosis (A) and McDonald 2017 multiple sclerosis (B) according to serum neurofilament light (NfL) levels.

Figure 3. Nomograms for predicting 2-year probabilities

Nomograms for predicting 2-year probabilities for clinically definite multiple sclerosis (MS) (A) and for McDonald 2017 MS (B) according to baseline neurofilament light (NfL), CSF, and brain MRI status.Categories for NfL: 0 (11.6–40.2 pg/mL), 1 (<11.6 pg/mL), 2 (>40.2 pg/mL). Categories for CSF oligoclonal bands (OCBs): 0 (absent), 1 (present). Categories for brain MRI T2 lesions: 0 (0 lesions), 1 (1–3 lesions), 2 (4–9 lesions), 3 (>9 lesions). To obtain the 2-year and 5-year survival probabilities, calculate trough use of the first row the points for every patient characteristic listed, then drop a vertical line from the total points row to the probabilities rows.