Clinically isolated syndrome: diagnosis and risk of developing clinically definite multiple sclerosis

In most cases, multiple sclerosis (MS) initially presents as clinically isolated syndrome (CIS). Differentiating CIS from other acute or subacute neurological diseases and estimating the risk of progression to clinically definite MS is essential since presenting a second episode in a short time is associated with poorer long-term prognosis. We conducted a literature review to evaluate the usefulness of different variables in improving diagnostic accuracy and predicting progression from CIS to MS, including magnetic resonance imaging (MRI) and such biofluid markers as oligoclonal IgG and IgM bands, lipid-specific oligoclonal IgM bands in the CSF, CSF kappa free light-chain (KFLC) index, neurofilament light chain (NfL) in the CSF and serum, and chitinase 3-like protein 1 (CHI3L1) in the CSF and serum. Codetection of oligoclonal IgG bands and MRI lesions reduces diagnostic delays and suggests a high risk of CIS progression to MS. A KFLC index > 10.6 and CSF NfL concentrations > 1150 ng/L indicate that CIS is more likely to progress to MS within one year (40-50%); 90% of patients with CIS and serum CHI3L1 levels > 33 ng/mL and 100% of those with lipid-specific oligoclonal IgM bands present MS within one year of CIS onset.