Neuroinflammatory Cerebrospinal Fluid Biomarkers as Predictors of Disease Progression in Multiple Sclerosis: Evidence from the Netherlands

Abstract

Background: |Cerebrospinal fluid (CSF) contains neuroinflammatory biomarkers, which are molecules measured in central nervous system fluid to track immune activation (neuroinflammation) and glial response. The most significant forms of such markers are STREM tool microgel activity, YKL-40 estradiol activation, and GFAP (astrogliosis), as well as cytokines such as TNF-alpha and IL-6, which aid in the diagnosis of inflammatory disorders and neurodegenerative issues. Objectives: The research objectives for studying neuroinflammatory cerebrospinal fluid CSF biomarkers and multiple sclerosis (MS) focus on identifying objective indicators of axonal injury, disability worsening, and glial activation. Our key targets include neurofilament light chain (NfL) and clinical and subclinical disease progression. A study of 250 participants was conducted at the Leiden University Medical Center (LUMC), located at Albinusdreef 2, 2333 ZA Leiden, Netherlands. The LUMC is the university hospital affiliated with Leiden University, of which it forms the medical faculty. Methods: The researchers follow the conventional IMRaD structure while incorporating advanced methodological and translational components expected in high-impact neurology and neuroimmunology journals. The researchers integrated neuroinflammatory biomarkers (e.g., neurofilament light chain, CXCL13, GFAP, sTREM2, and cytokines) with clinical progression and precision medicine approaches. Furthermore, we quantified baseline CSF levels of neuroinflammatory and neurodegenerative molecules in early-stage and progressive MS cohorts. We then correlated specific CSF biomarker concentrations with longitudinal changes in clinical disability scores, such as the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSS). Lastly, the researchers differentiated biomarkers reflecting acute relapse-associated inflammation from those tracking silent Progression Independent of Relapse Activity (PIRA). Results: CSF neuroinflammatory biomarkers predict multiple cellular processes in MS progression by tracking distinct pathological processes. The researchers found elevated neurofilament light and heavy chains (NfL/NfH) and glial fibrillary acidic protein (GFAP), which strongly correlated with extraordinarily rapid external damage, non-relapsing disability progression, and worst severity scores, which were delinquent in nature. Conclusions: We found that CSF neuroinflammatory and neurodegenerative biomarkers effectively tracked and predicted multiple sclerosis disease severity and long-term disability progression. We found that biomarkers like neurofilaments and glial fibrillary acidic protein (GFAP), followed by chemokine ligands, bridge the gap between acute relapse activity and chronic smoldering pathology.