Relevance of KFLC quantification to differentiate clinically isolated syndrome from multiple sclerosis at clinical onset

Objective: The objective of the research was to evaluate diagnostic and predictive value for determination of KFLC in cerebrospinal fluid (CSF) compared to the qualitative procedure of OCB determination in patients with CIS who converted to MS during a two-year period.

Patients and methods: KFLC, total immunoglobulin G (IgG), serum albumin and CSF albumin were determined with an immunonephelometric method in 151 patients with suspected MS who were admitted to the Neurology Clinic while CSF/serum quotients (QKFLC, QIgG and QAlb) and indexes were calculated with regards to albumin (QCSF/Qserum). Presence of OCBs was determined by isoelectric focusing with immunofixation. Based on their clinical, OCB and magnetic resonance imaging (MRI) findings, 50 patients were classified as other neurological disorder patients (OND), and 101 patients were classified as CIS, 50 of which converted to MS during the two-year period. ROC analysis, ROC curve comparisons and comparison of median KFLC parameters were used to find optimal cut-off with regards to CIS diagnosis and conversion to MS.

Results: CSF KFLC median was 2,01 mg/L in MS group contrary to 0,68 mg/L and 0,17 mg/L in CIS and OND group, and KFLC index was 33,52 mg/L contrary to 9,68 mg/L and 3,71 mg/L (p < 0,0001). ROC analysis for accuracy of detection of intrathecal synthesis for QKFLC and KFLC index showed an AUC of 0,891 and 0,839 and the cut-off of 0,027 and 8,82, respectively (sensitivity 73,2% and 71,3%; specificity 96,0% and 98,0%; +PV 97,4% and 98,6%). The diagnostic accuracy of KFLC index for conversion from CIS to MS showed AUC of 0,840 and a cut-off of 9,092 (sensitivity 90,0%; specificity 73,3%; -PV 93,7%). Life age correlates significantly with serum KFLC (r = 0,34; p < 0,0001) and through aging process lower KFLC indexes can be expected, i.e. likelihood of false negative diagnoses.

Conclusion: KFLC index showed diagnostic value, although it is not more specific and more sensitive than OCB. Application of KFLC might serve as a screening method while OCB could be used in uninterpretted cases only. Patients who converted to MS have significantly higher KFLC which can contribute to an early diagnosis and prompt therapy with its predictive role.