Biological Markers in Early Multiple Sclerosis: the Paved Way for Radiologically Isolated Syndrome

Abstract

Radiologically Isolated Syndrome (RIS) is characterized by MRI-typical brain lesions fulfilling the 2009 Okuda criteria, detected in patients without clinical conditions suggestive of MS. Half of all RIS patients convert to MS within 10 years. The individual course of the disease, however, is highly variable with 12% of RIS converting directly to progressive MS. Demographic and imaging markers have been associated with the risk of clinical MS in RIS: male sex, younger age, infra-tentorial, and spinal cord lesions on the index scan and gadolinium-enhancing lesions on index or follow-up scans. Although not considered as a distinct MS phenotype, RIS certainly shares common pathological features with early active and progressive MS. In this review, we specifically focus on biological markers that may help refine the risk stratification of clinical MS and disability for early treatment. Intrathecal B-cell activation with cerebrospinal fluid (CSF) oligoclonal bands, elevated kappa free light chains, and cytokine production is specific to MS, whereas neurofilament light chain (NfL) levels reflect disease activity associated with neuroaxonal injury. Specific microRNA profiles have been identified in RIS converters in both CSF and blood. CSF levels of chitinases and glial acidic fibrillary protein (GFAP) reflecting astrogliosis might help predict the evolution of RIS to progressive MS. Innovative genomic, proteomic, and metabolomic approaches have provided several new candidate biomarkers to be explored in RIS. Leveraging data from randomized controlled trials and large prospective RIS cohorts with extended follow-up to identify, as early as possible, biomarkers for predicting greater disease severity would be invaluable for counseling patients, managing treatment, and monitoring.

Plasma glial fibrillary acidic protein levels correlate with paramagnetic rim lesions in people with radiologically isolated syndrome

“…47 While markers like NfL and GFAP have gained traction, the search continues for other blood-based markers that can provide insights into disease activity and progression, including pro-inflammatory cytokines, chemokines and ribonucleic acids. 48…”

Gut Microbial Metabolome and Dysbiosis in Neurodegenerative Diseases: Psychobiotics and Fecal Microbiota Transplantation as a Therapeutic Approach—A Comprehensive Narrative Review

“…Metabolomic evaluation has shown lower levels of tryptophan in MS patients compared to controls [242,244]. Differences in tryptophan metabolism have also been found in progressive multiple sclerosis compared to controls or relapsing-remitting MS (RRMS) [243,247].…”

How Early Is Early Multiple Sclerosis?

“…In order to be able to identify these individuals early, the development of accurate biomarkers is absolutely crucial. Furthermore, the development of biomarkers will enrich our knowledge and understanding of MS pathology, and they will also provide potential targets for the development of novel therapies [ 60 ].…”