Diagnostic value of the kappa free light chain index in multiple sclerosis under the 2024 CSF positivity criterion: a multicentre study in oligoclonal band-negative patients

Introduction: The kappa free light chain index (κ-FLC) has been established as an alternative to oligoclonal bands (OCB) for defining cerebrospinal fluid (CSF) positivity, which can contribute to a multiple sclerosis (MS) diagnosis by the 2024 revised MS diagnostic criteria. This study aimed to evaluate the contribution of the κ-FLC index to the diagnosis of MS, through the CSF positivity criterion, in OCB-negative patients. Methods: OCB-negative patients, diagnosed with MS at any time according to the 2017 McDonald criteria, were included in this multicentre retrospective study. CSF positivity was defined by a κ-FLC index ≥ 6.1. Results: Among 141 enrolled patients, 117(83%) patients had measurable CSF κ-FLC, with a median κ-FLC index of 7.2 (IQR: 4.5-12.7) and 61 patients (43%) had a positive (≥ 6.1) κ-FLC index. A MS diagnosis was met at the time of the lumbar puncture in 102 patients, through the fulfilment of both the 2017 dissemination in space (DIS) and time (DIT) criteria. Among the remaining 39 patients, MS diagnosis was met following a relapse in 11 (28%) and based on follow-up MRI findings in 28 patients (72%). Among the 34 patients meeting DIS but not DIT criteria, 16 (47%) had a κ-FLC index ≥ 6.1. Considering the contribution of the κ-FLC index to the CSF positivity criterion, a MS diagnosis could have been anticipated in these patients by a median of 4.9 months (IQR: 1.8-14.1). Conclusion: In the context of the CSF positivity criterion of the revised 2024 MS diagnostic criteria, the κ-FLC index may contribute to an earlier MS diagnosis in OCB-negative patients fulfilling the DIS but not the DIT criteria.