CSF biomarkers in multiple sclerosis: beyond neuroinflammation

Abstract

For many years, quantifiable biomarkers in neurological diseases have represented a hot topic. In multiple sclerosis (MS), cerebrospinal fluid biomarkers have played a diagnostic role since the introduction of Poser's criteria in 1983, with IgG oligoclonal bands playing a supporting role in an epoch prior to magnetic resonance imaging and a complementary one after the introduction of McDonald criteria in 2001. Nowadays, that supporting role has turned into a main one in substituting for dissemination in time and defining the diagnosis of MS in patients with a first clinical event, according to the 2017 revised McDonald criteria. Possibly kappa free light chains, N-CAM, chitinase 3-like protein 1 and IgM oligoclonal bands, not yet implemented in clinical practice, could similarly gain importance in the near future. Furthermore, the increasing knowledge of molecular mechanisms leading to chronic inflammation has enhanced interest in looking for biomarkers of disease activity, better defining the MS phenotype and patients with highly active disease. Accordingly, myelin proteins, intermediate filaments, metalloproteinases and other molecules involved in the inflammatory cascade, are currently under investigation. Finally, it has long been known that axonal loss occurs from the early phases, leading to a progressive neurological deterioration. Since established criteria to assess treatment failure and transition to progressive forms are still lacking, both treatment response and prognostic biomarkers would be useful to predict MS course, and neurofilaments seem to have this potential. The purpose of this review article was to illustrate biomarkers that have been already validated or require further validation after proving to be useful in exploratory studies and potentially could prove useful in clinical practice in the coming years.

Digital Twins for Multiple Sclerosis

“…Taking the patient's history is traditionally the first important step in the evaluation of pwMS, which focuses on relapses and/or disease progression in the different neurological functional systems. Contextual parameters including lifestyle factors, comorbidities (122), psychological factors, emotions and sociodemographic factors (123)(124)(125) must also be recorded, assessed through the medical record and the conversation between physician and patient. There are attempts to standardize and quantitate MS relevant neurological history, such as e.g.…”

“…Implementing standard lab data from clinical practice into a comprehensive approach of DTMS can complete the fundamental quest of real world evidence for individually improved treatment decisions and balanced therapeutic risk assessment ( 140 , 141 ). As the MS disease process takes place in the CNS, analysis of cerebral spinal fluid is of high importance ( 123 , 124 ). In addition to emerging immunological and neurobiological biomarkers, new technologies could be used for data collection for the DTMS as it has been described by Meyer zu Hörste ( 136 ) and will be described among multi-omics approaches.…”

N-Glycomics of Cerebrospinal Fluid: Method Comparison

“…Molecules 2021, 26, x FOR PEER REVIEW 2 of 10 disease (AD), mild cognitive impairment (MCI), multiple sclerosis (MS), Parkinson's, and other related diseases [18][19][20][21]. However, it has long been known that in early, presenile, and atypical cases, and in the presence of comorbidities, the diagnostic accuracy of current biomarkers may drop substantially [16].…”

“…Its direct contact with the brain and spinal cord makes this fluid a reliable analytical sample for the identification of biochemical changes that occur during the progression of neurodegenerative diseases [ 10 , 16 , 17 ]. Currently, CSF is a source of biomarkers for diagnostic workups of Alzheimer’s disease (AD), mild cognitive impairment (MCI), multiple sclerosis (MS), Parkinson’s, and other related diseases [ 18 , 19 , 20 , 21 ]. However, it has long been known that in early, presenile, and atypical cases, and in the presence of comorbidities, the diagnostic accuracy of current biomarkers may drop substantially [ 16 ].…”

Potential Biomarkers Associated with Multiple Sclerosis Pathology

“…In recent years, several remarkable reviews have been published that highlight the importance of biomarkers in the prediction, diagnosis, and outcome of treatments in MS e.g., [ 15 , 16 , 17 , 18 ]. In this physically and mentally disabling disease, being able to make relevant information on the potential best biomarkers easily accessible to MS-clinicians is essential for daily practice.…”