Clinically Isolated Syndrome (CIS), Multiple Sclerosis
Conditions
Keywords
multiple sclerosis, clinically isolated syndrome, cerebrospinal fluid, kappa free light chains, oligoclonal bands, biomarker, diagnosis
Brief summary
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.
Detailed description
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.
Interventions
DIAGNOSTIC_TESTOligoclonal bands and kappa free light chains (KFLC)
Comparison of oligoclonal bands and kappa free light chains (KFLC) in patients with multiple sclerosis (MS) / clinically isolated syndrome (CIS)
Sponsors
Skripuletz, Thomas Prof. Dr.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Non-inferiority of diagnostic sensitivity of cerebrospinal fluid (CSF) kappa free light chains (KFLC) in multiple sclerosis (MS) and clinically isolated syndrome (CIS) compared to oligoclonal bands | From study inclusion to the final analysis of cerebrospinal fluid (CSF) oligoclonal bands and kappa free light chains (KFLC) at 12 months | Evidence of an intrathecal kappa free light chains (KFLC) synthesis is equally sensitive to assess for an intrathecal immunglobulin synthesis compared with oligoclonal bands |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Superiority of Reiber´s diagram for kappa free light chains (KFLC) compared to KFLC index of 6.1 to assess for an intrathecal KFLC synthesis in multiple sclerosis (MS) and clinically isolated syndrome (CIS) patients | From study inclusion to the final analysis of cerebrospinal fluid (CSF) oligoclonal bands and kappa free light chains (KFLC) at 12 months | The frequence of an intrathecal kappa free light chains (KFLC) synthesis as assessed by Reiber´s diagram is significantly higher as compared to the KFLC index of 6.1 as cut-off |
Countries
Germany
Outcome results
None listed