Up to date prognostic estimation in newly diagnosed patients is hardly possible while the differentiation between disabling versus more benign courses is of utmost relevance. Reliable blood-based biomarkers that are associated with diagnosis and prognosis of multiple sclerosis (MS) have not been established.
Can serum neurofilament light chain measurements serve as a reliable biomarker for diagnostic accuracy and prognosis for multiple sclerosis patients at the time point of diagnosis?
In a multicenter prospective longitudinal observational cohort, patients with a first diagnosis of multiple sclerosis (MS) or clinically isolated syndrome (CIS) were recruited between August 2010 and November 2015 in 22 centers and assessed yearly with a standardized protocol. Patients were offered standard immunotherapies according to national treatment guidelines. Serum NfL concentrations were measured using an ultrasensitive single-molecule array (Simoa).
A possible association between sNfL levels and clinical diagnosis, relapses, MRI parameters and treatment decisions was tested in 814 patients classified according to current (2017) and older (2010) McDonald criteria at time point of diagnosis and two years after study inclusion sNfL levels correlated with number of T2 and Gd+ lesions and clinical relapses. After reclassification of CIS patients with existing CSF analysis, according to 2017 criteria, sNfL levels were lower in CIS than RRMS patients (9.1 pg/ml, IQR 6.2-13.7 pg/ml, n = 45; 10.8 pg/ml, IQR 7.4-20.1 pg/ml, n = 213; p = 0.036) and increased accuracy of distinction between CIS and RRMS, when including ≥ 90th percentile of sNfL values. Patients receiving disease-modifying treatment (DMT) during the first two years had higher sNfl baseline levels (11.8 pg/ml, 7.5-20.9 pg/ml, n = 727) than patients never receiving DMT (9.5 pg/ml, IQR 6.4-14.1 pg/ml, n = 87, p = 0.002). Longitudinal sNfL levels reflected treatment decisions within the first four years.
sNfL is associated with diagnosis and prognosis of MS patients at the time point of first diagnosis and may be of use for initial treatment stratification.