“We split the population into those with a high intrathecal kappa free light chain synthesis and those with a low intrathecal kappa free light chain synthesis,” he said. “And in those patients with a high synthesis rate, there is basically no difference which parameter you use. But in patients with a lower kappa free light chain synthesis, the absolute kappa free light chain concentration in CSF is inferior compared with the kappa free light chain index.”
When comparing the κ-FLC index to oligoclonal banding, he said, it’s worth noting that OCBs detect an intrathecal IgG synthesis. The intrathecal κ-FLC index is increased in the case of an IgG synthesis but also in the case of an IgM and IgA synthesis.
Turning to the prognostic value of κ-FLC, Dr. Hegen cited a study in which he and coauthors investigated whether the κ-FLC index predicts MS disease activity independent of demographics, clinical characteristics, and MRI findings (Berek K, et al. Neurol Neuroimmunol Neuroinflamm. 2021;8[4]:e1005).
Ninety percent of patients with MS are positive for OCBs, and patients who are positive have a worse disease course, he noted. “Is it possible to use the kappa free light chain index to further stratify this big proportion of patients? Does it make a difference if a patient is positive with a low κ-FLC index or positive with a high κ-FLC index?” he asked.
Patients with early MS who had CSF and serum sampling at disease onset were followed for four years.
Their findings: Patients with a κ-FLC index greater than 100 at baseline had a twice as high probability for a second clinical attack within 12 months than patients with a low κ-FLC index. Within 24 months, the chance in patients with a high κ-FLC index was four times as high as in patients with a low κ-FLC index.
“This was also seen in the multivariate model,” Dr. Hegen said. “When adjusting for disease duration, for example, or for different MRI activity, the κ-FLC index remained an independent predictor of future disease activity—in this case of time to second clinical attack.”
In a study published last year, Dr. Hegen and coauthors found that the κ-FLC index predicts even long-term disease activity independently of other risk factors (Berek K, et al. Mult Scler. 2025;31[10]:1187–1194).
Also published last year was a study aimed at identifying prognostic risk factors at radiologically isolated syndrome diagnosis associated with the development of MS symptoms (Fissolo N, et al. JAMA Neurol. 2025;82[7]:722–733). “These are patients who have no clinical signs and symptoms of MS, but they have a brain MRI with lesions that look like MS,” said Dr. Hegen, a coauthor. “And some of them develop clinical symptoms and some of them develop clinically MS.” The authors reported that having a κ-FLC index of 6.1 or higher was strongly associated with developing MS symptoms.
Dr. Hegen closed with a case to illustrate the diagnostic difference the κ-FLC index can make.
A 30-year-old female patient presented with left-side optic neuritis with typical symptoms: blurred vision, pain on eye movement, and decreased color vision. A brain MRI scan showed a juxtacortical lesion and a periventricular lesion, both without contrast enhancement. The patient also received a lumbar puncture; CSF was normal and OCBs were negative.
The 2017 McDonald criteria were not fulfilled—there was no dissemination in time and no inflammatory CSF—and thus the diagnosis of MS could not be made.
However, the κ-FLC index was elevated at 9.1, and when the upcoming 2024 McDonald criteria were applied, he said, the criteria were met. In the new criteria, positive CSF means either positive OCBs or an elevated κ-FLC index. “In this case, we have the dissemination in space seen in the brain MRI plus a positive CSF shown by the elevated kappa free light chain index, and therefore we can make the diagnosis of MS.”
The six-month follow-up brain MRI results revealed the patient had developed new brain MRI lesions. “So this was a very clear case,” Dr. Hegen said.
Amy Carpenter is CAP TODAY senior editor.