36.3. Prognostic significance of CSF FLCs

Chapter 36

The prognostic value of IgG oligoclonal bands in predicting clinical outcomes in CIS is well established [935], and emerging data suggest that FLCs may have similar prognostic relevance [898][855][890][934]. Villar et al. [855] investigated whether κ FLC CSF concentrations in patients with CIS were predictive of conversion to MS. The study included 78 consecutive CIS patients and 25 controls (patients with non-inflammatory neurological diseases). A cut-off value of κ FLC CSF >0.53 mg/L (defined as the mean + 2 standard deviations for the control group) identified CIS patients with an increased probability of conversion to MS (p<0.0001). In a multivariate Cox regression analysis (adjusted for gender, age and basal MRI findings), the hazard ratio was 6.41 (p<0.003).

The prognostic value of κ FLC CSF concentrations was confirmed in a study of 77 CIS patients by Menendez Valladares et al. [890], using a cut-off of >0.38 mg/L to identify patients at increased risk of MS (p<0.0001). The same research group subsequently reported the predictive value of the κ FLC index to identify CIS patients at highest risk of conversion to MS, using a cut-off of 10.62 (defined by ROC analysis) [898]. CIS patients with a κ FLC index >10.62 had a 7.3-fold higher risk of progression compared with those with an index below this value (Figure 36.6, p<0.0001). On multivariate Cox regression analysis (that also included the patient’s age, sex, and the dissemination of lesions in space by MRI), the κ FLC index remained prognostic for conversion to MS.

Conversely, Presslauer et al. [853] did not find a significant difference in the κ FLC index values between stable CIS patients and those who underwent conversion to MS, but the number of patients was small (n=24). Therefore, the prognostic value of FLC CSF measurements warrants further investigation.


  1. Why should a κ FLC index be used in preference to κ FLC concentrations to identify intrathecal immunoglobulin synthesis?


  1. Because correcting CSF κ FLC values using albumin measurements provides an indicator of whether the FLCs were produced locally, or have diffused from the blood due to blood/brain barrier dysfunction (Section 36.1).