# Baseline neurofilament light chain and brain-derived neurotrophic factor levels predict development of aggressive multiple sclerosis

## TL;DR

This study finds that early cerebrospinal fluid levels of NFL and BDNF can predict aggressive multiple sclerosis, helping identify patients who need early treatment.

## Contribution

The study identifies NFL and BDNF as novel biomarkers for predicting aggressive MS in early disease stages.

## Key findings

- AMS patients had higher NFL and lower BDNF levels compared to non-AMS patients.
- NFL and BDNF levels correlated with disease progression markers like EDSS scores and MRI lesions.
- BDNF showed high specificity in predicting AMS conversion.

## Abstract

Patients with multiple sclerosis (MS) may present with a rapidly disabling clinical course in the first few years of disease. It is imperative to find biomarkers to predict patients with aggressive MS (AMS) and have an opportunity to prevent disability accumulation through appropriate treatment strategies. Our aim was to explore the prognostic value of neurofilament light chain (NFL) and brain-derived neurotrophic factor (BDNF) levels in cerebrospinal fluid (CSF) obtained in the early stages of MS.

Relapsing-remitting multiple sclerosis (RRMS) patients presenting with first-time attacks were screened, of which 26 fulfilled AMS criteria in the 3-year follow-up period. In addition, 27 age/sex-matched RRMS patients without AMS (non-AMS) were included. Baseline NFL and BDNF levels were measured in CSF obtained during the remission period following the first MS attack. Disease activity was monitored for 3 years by periodic expanded disability status scale (EDSS), cranial-spinal MRI assessments, and no evidence of disease activity (NEDA)-3 was determined.

AMS patients showed significantly higher attack numbers, EDSS scores, MRI lesions, and baseline NFL levels compared to non-AMS patients. Baseline BDNF levels were significantly lower than in non-AMS patients. NFL/BDNF levels were correlated with number of attacks and/or EDSS scores at the third year follow-up. Patients with NEDA-3 showed significantly lower baseline NFL and higher BDNF levels than those without NEDA-3. Receiver operating characteristic curve analysis showed the highest specificity for CSF BDNF measurements in predicting AMS conversion.

Baseline NFL and BDNF levels effectively predict the development of AMS emerging early in the course of MS. Combined use of these molecular markers with MRI results may enable early diagnosis and appropriate therapeutic intervention of AMS.