University Medical Center of the Johannes Gutenberg University Mainz
Department of Neurology

Author Of 2 Presentations

Biomarkers and Bioinformatics Poster Presentation

P0159 - Serum NfL predicts disability progression in MS in a six year longitudinal cohort study (ID 1196)

Speakers
Presentation Number
P0159
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Immunomodulatory therapies are effective in controlling disability progression in patients with multiple sclerosis (MS). Nonetheless, markers are needed to predict disease progression and transition into secondary progressive MS (SPMS) in order to guide individual treatment regimens.

Objectives

Evaluating the temporal evolution of neurofilament light chain (NfL) in patients with relapsing-remitting MS (RRMS) and its ability for forecasting EDSS progression and SPMS conversion within the prospective Neurofilament and long-term outcome in MS (NaloMS) cohort.

Methods

196 patients (median age 35.0 years (interquartile range (IQR) 27.2-43.1), 69.9% (n=137) female) with relapsing-remitting MS (RRMS) or clinically isolated syndrome were followed for median six years (IQR 4-8). Serum was collected at baseline and follow-up (FU); serum NfL (sNfL) levels were measured by single molecule array.

Results

During the study period, 34 of 196 patients (17%) suffered from relapse-free EDSS-progression (RFP) one year prior to FU and 27 of 196 patients (14%) converted to SPMS at FU. sNfL at Baseline was increased in patients with RFP, which remained significant after multivariate correction. Baseline sNfL levels ≥ 7.3 pg/ml were associated with increased probability of RFP in Kaplan-Meier analysis. In addition, sNfL levels at FU were increased in SPMS-converters and temporal NfL increases were more frequent in patients transitioning to SPMS than in non-converters.

Conclusions

sNfL levels at baseline predict disability progression at median six year follow-up in a prospective longitudinal cohort study. Moreover, sNfL levels are more frequently increased at follow-up compared to baseline in patients transitioning to SPMS. Therefore, temporal evolution of sNfL might thus be an ancillary tool facilitating timely SPMS diagnosis.

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Diagnostic Criteria and Differential Diagnosis Poster Presentation

P0263 - Serum neurofilament predicts clinical progression and increases diagnostic accuracy in patients with early multiple sclerosis (ID 1336)

Abstract

Background

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.

Objectives

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?

Methods

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).

Results

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[2010] patients with existing CSF analysis, according to 2017 criteria, sNfL levels were lower in CIS[2017] than RRMS[2017] 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.

Conclusions

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.

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