Prognostic value of serum neurofilament light in multiple sclerosis

Abstract

Background Multiple sclerosis is a heterogenous, chronic, inflammatory-demyelinating disease affecting the central nervous system, with approximately 2.9 million cases worldwide and 13 500 in Austria as of 2020. It predominantly affects young female adults with a mean age at disease onset of 32 years and a 2:1 female to male ratio worldwide. In the early stages of the disease axons and neurons are mostly preserved, but as the disease progresses, there is gradual neuro-axonal loss, which can result in cognitive impairment and physical disability. Serum neurofilament light chain (sNfL) has shown to be a promising biomarker for assessing neuroaxonal injury in persons with multiple sclerosis (pwMS), supported by substantial evidence. In cross-sectional studies, sNfL has been associated with markers of disease activity such as relapses, structural brain magnetic resonance imaging (MRI) changes or clinical parameters of disability, e.g. the Expanded Disability Status Scale (EDSS). However, it is still unclear to which extent in particular high sNfL levels impact on subsequent disease evolution. Methods The presented thesis comprises a longitudinal study in 199 pwMS (median age 34.2 years, 64.3% female) and 49 controls from the neurological outpatient department at the Medical University of Graz, Austria. This study is part of the MarkMS study, which is registered at www.clinicaltrials.gov under NCT04892134. All pwMS underwent 3-Tesla MRI to assess global and compartmental normalized brain volumes, T2-lesion load and cortical mean thickness. In 144 pwMS a follow-up for clinical data, MRI data and serum samples was available (median follow-up time 3.8 years). Linear and binary logistic models were used to estimate the independent contribution of sNfL for changes in MRI measures and EDSS. Age-corrected sNfL z-scores from a normative database of healthy controls were used for sensitivity analyses. Results High sNfL levels at baseline were associated with atrophy measures of the whole brain (standardized beta coefficient β j= -0.352, p

Datum der Bewilligung	2025
Originalsprache	Englisch
Gradverleihende Hochschule	Medizinische Universität Graz
Betreuer/-in	Michael Khalil (Betreuer*in) & Christian Enzinger (Betreuer*in)