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Updated: Aug 11, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
High levels of kappa free light chain synthesis predict cognitive decline in relapsing-remitting multiple sclerosis
Igal Rosenstein1, Markus Axelsson1, Lenka Novakova1
1Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Background:
Evolving evidence suggests that measurement of cerebrospinal fluid (CSF) kappa free light chain (KFLC) synthesis has high diagnostic sensitivity and specificity for multiple sclerosis (MS), but its prognostic ability is less investigated. The usefulness of KFLC in predicting cognitive impairment (CI) is still unknown.
Methods:
In a monocentric longitudinal retrospecitve cohort study, KFLC-index ([CSF KFLC/serum KFLC]/[CSF albumin/serum albumin]) measured by latex-enhanced immunonephelometry was prospectively determined as part of the diagnostic workup in patients with early relapsing-remitting MS (RRMS, n=77). The ability of KFLC-index to predict information processing speed (IPS) worsening as assessed with the symbol digit modalities test (SDMT) was investigated in univariable and multivariable models.
Results:
In patients with KFLC-index>100 (n=31), 11 subjects (35.5%) showed reduced SDMT scores by ≥8 points at follow-up (mean follow-up time 7.3 ± 2.6 years), compared with their baseline scores (p=0.01). Baseline KFLC-index>100 was strongly associated with a higher hazard of SDMT score reduction at follow-up (adjusted hazard ratio 10.5, 95% confidence interval 2.2-50.8, p=0.003; median time to SDMT reduction 7 years).
Conclusion:
Intrathecal KFLC synthesis has become an attractive diagnostic tool for MS. We show for the first time that in a real-world setting of early RRMS, KFLC-index predicted cognitive decline. Whether this predictive ability of KFLC-index also concerns other cognitive domains than IPS, warrants further investigations.
Insights
Cerebrospinal fluid kappa free light chain index predicts cognitive decline in early multiple sclerosis patients. Elevated levels indicate a higher risk of information processing speed worsening over time.
Area of Science:
- Neurology
- Immunology
- Biomarker Research
Background:
- Multiple sclerosis (MS) diagnosis increasingly utilizes cerebrospinal fluid (CSF) kappa free light chain (KFLC) synthesis.
- Prognostic value of KFLC for MS progression, particularly cognitive impairment, remains under-investigated.
Purpose of the Study:
- To evaluate the prognostic ability of KFLC-index in predicting cognitive impairment in early relapsing-remitting MS (RRMS).
- To assess the association between KFLC-index and worsening of information processing speed (IPS).
Main Methods:
- A monocentric, longitudinal, retrospective cohort study of 77 early RRMS patients.
- KFLC-index calculated using CSF and serum KFLC and albumin levels, measured via latex-enhanced immunonephelometry.
- Information processing speed assessed using the Symbol Digit Modalities Test (SDMT) at baseline and follow-up.
Main Results:
- Patients with KFLC-index > 100 showed a 35.5% rate of significant SDMT score reduction over a mean follow-up of 7.3 years.
- Baseline KFLC-index > 100 was a strong predictor of SDMT score reduction (adjusted hazard ratio 10.5, p=0.003).
- Median time to SDMT score reduction was 7 years in patients with elevated KFLC-index.
Conclusions:
- Intrathecal KFLC synthesis, indicated by KFLC-index, is a valuable diagnostic marker for MS.
- This study demonstrates for the first time that KFLC-index predicts cognitive decline in early RRMS in a real-world setting.
- Further research is needed to determine if KFLC-index predicts decline in other cognitive domains beyond IPS.
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