Advances in Multiple Sclerosis Diagnostic Criteria
This video was recorded prior to the release of the 2024 McDonald criteria1 in September 2025.
The 2024 McDonald criteria include CSF Kappa Free Light Chain Index measurements
"The κFLC-index is interchangeable with oligoclonal bands and consequently can substitute for oligoclonal bands for diagnosis"
Montalban Lancet Neurol 20251
"In some labs the determination of OCB is not so easy, it’s not a trivial procedure, so I think that will be a very helpful tool in some labs around the world.”
Prof. Xavier Montalban2, Chair of the International Advisory Committee on Clinical Trials in Multiple Sclerosis
Image of attendees at ECTRIMS 2024
The proposed revision of the diagnostic criteria was first presented at European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) conference 20243,4.
CSF Kappa Free Light Chain (FLC) measurements identify intrathecal immunoglobulin synthesis
Intrathecal immunoglobulin synthesis is a hallmark of MS5,6.
During inflammation in the central nervous system, plasma cells release immunoglobulins within CSF. This process is known as intrathecal immunoglobulin synthesis5.
When immunoglobulins are secreted, Kappa FLC, a portion of the immunoglobulin, are also secreted.
Impaired blood-to-CSF barriers can also cause immunoglobulins and Kappa FLC to appear in CSF, so their origin needs to be distinguished7.
Kappa Index is a calculation that includes albumin measurements. This helps confirm that the presence of CSF Kappa FLC is due to intrathecal immunoglobulin synthesis and Kappa FLC do not originate from serum7.
Increased Kappa Index is an indicator of a humoral immune response within the central nervous system.
A Kappa FLC Index result above 6.1 is defined as 'CSF positive'1.
Revision of diagnostic criteria for MS reflects advances in technology
The detection of CSF-restricted oligoclonal IgG bands (OCB) is the traditional approach for proving intrathecal immunoglobulin synthesis6.
The 2024 McDonald criteria recognize CSF Kappa FLC Index as interchangeable with OCB testing1.
Sensitivity range
|
Specificity range
|
||
|---|---|---|---|
32 studies concluded diagnostic sensitivity and specificity are very similar for Kappa Index and OCB7.These studies included 3,322 patients with Clinically Isolated Syndrome and Multiple Sclerosis, and 5,849 controls. |
Kappa Index |
52-100%
|
69-100%
|
OCB |
37-100%
|
74-100%
|
|
Mean difference |
+2% |
-4% |
Adapted from Hegen Mult Scler 20227
“Kappa Index has several advantages over oligoclonal band detection. […] its quantitative nature and its automated operator independent output, which makes results available within a few hours, is important and may be even crucial for treatment decisions for clinicians”.
Dr Diana Ferraro, Head of Multiple Sclerosis Center at Baggiovara Hospital, University Hospital of Modena
Listen to this exclusive interview with Dr Diana Ferraro
Dr Ferraro discusses how ordering CSF Kappa FLC in the MS workup has improved diagnostic accuracy and identified more MS patients:
This video was recorded prior to the release of the 2024 McDonald criteria1 in September 2025.
References
- Montalban X, et al. Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. Lancet Neurol 2025; 24:850-865. Available here
- ECTRIMS. The ECTRIM Podcast – Episode 26. 2024 [02/2025]; Available from: https://ectrims.eu/podcast/episode-26-efforts-towards-a-better-ms-diagnostic-criteria/.
- MS Trust. McDonald criteria. 2025 [02/2025]; Available from: https://mstrust.org.uk/a-z/mcdonald-criteria.
- ECTRIMS. McDonald Diagnostic Criteria. 2024 [02/2025]; Available from: https://ectrims.eu/mcdonald-diagnostic-criteria.
- Hegen H, et al. Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A consensus statement. Mult Scler 2022; 29:182-195
- Thompson AJ, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 2018; 17:162-173
- Hegen H, et al. Cerebrospinal fluid kappa free light chains for the diagnosis of multiple sclerosis: A systematic review and meta-analysis. Mult Scler 2022; 29:169-181