The goal of this observational study is to learn about the role of kappa free light chains (KFLC) in cerebrospinal fluid (CSF) in the diagnosis of multiple sclerosis (MS) and clinically isolated syndrome (CIS). The main question it aims to answer is:

Are KFLC superior, inferior or equally useful in the diagnostic work-up of CSF of patients with MS and CIS?

In CSF and serum sample pairs of patients diagnosed with MS or CIS, KFLC are measured using a nephelometric assay and are compared with the gold standard, of CSF diagnostics, oligoclonal bands.

In this multicenter study, paired cerebrospinal fluid (CSF) and serum samples from patients with chronic inflammatory diseases of the central nervous system (multiple sclerosis (MS) / clinically isolated syndrome (CIS)) are investigated to evaluate the diagnostic utility of CSF-specific oligoclonal bands and kappa free light chains (KFLC). Both biomarkers have already demonstrated diagnostic relevance in this patient population, but comparative multicenter studies are still lacking. Another key challenge for the clinical implementation of KFLC is the absence of standardized reference values, as different cut-offs were proposed.

To address this gap, CSF-specific oligoclonal bands and KFLC are prospectively analyzed in a multicenter cohort of patients with MS / CIS. Samples and associated data are collected prospectively and partially retrospectively from participating centers. Included patients are followed longitudinally to determine whether conversion from CIS to clinical definite MS occurs and to monitor disease progression over time.

Inclusion Criteria:

• patients diagnosed with multiple sclerosis (MS) or clinically isolated syndrome (CIS) according to 2017-revised McDonald criteria for MS
• age between 18 and 70 years

Exclusion Criteria:

• no diagnosis of MS or CIS according to 2017-revised McDonald criteria for MS
• no available cerebrospinal fluid (CSF) and serum sample pairs

Patients being adult, diagnosed with multiple sclerosis (MS) or clinically isolated syndrome (CIS), receiving a cerebrospinal fluid (CSF) analysis as part of the clinical routine diagnostic work-up

Pseudonym, immunoglobulin (Ig) G serum (g/l), IgG cerebrospinal fluid (CSF) (mg/l), Q IgG, Albumin serum (g/l), Albumin CSF (mg/l), Q-Albumin

27.10.2022 beginning ending 10 years after publication

Individual participant data (IPD) will be stored and processed in pseudonymized form on the server of the computing center of Hannover Medical School (MHH) in compliance with data protection regulations, in particular the EU General Data Protection Regulation (GDPR). Access to the pseudonymized data and their processing will be restricted to authorized study team members who are bound by confidentiality obligations. Unused data will be deleted. Remaining data will be archived for ten years after study completion in accordance with good scientific practice guidelines and will be irreversibly deleted thereafter. No external parties will have access to the IPD or supporting information.