ABSTRACT
OBJECTIVES: Oligoclonal bands (OCB) analysis is the reference standard for detecting an intrathecal IgG synthesis. Alongside OCB, free light chains kappa (FLCκ) are considered an additional sensitive biomarker for determining patterns 2 or 3, indicating intrathecal Ig synthesis. However, kFLC IF is not suitable for detecting a monoclonal pattern 5. The primary aim of this study was to evaluate the impact of incorporating FLCκ analysis into routine cerebrospinal fluid (CSF) diagnostics instead of OCB testing on the rate of missed monoclonal IgG detection. METHODS: A two-center retrospective biomarker study was conducted. OCB were identified using isoelectric focusing in polyacrylamide gels followed by silver staining or in agarose gels followed by immunofixation. FLCκ were quantified using nephelometry and FLCκ assay (Siemens). RESULTS: Out of a combined total of 17,755 OCB analyses conducted between 2011 and 2021, a subset of 269 cases (1.5â¯%) exhibited pattern 5. 98 samples (36â¯%), which included 18 samples with intrathecal inflammation as determined by additional OCB pattern 2 were included in the FLCκ analysis. Of those, 16 (89â¯%) had intrathecal FLCκ synthesis. CONCLUSIONS: While FLCκ offers a promising avenue for detecting an intrathecal inflammation, the pattern 5, though rare, remains a valuable additional finding of OCB analysis. A combined approach of FLCκ and OCB analysis is recommended for a comprehensive assessment of the humoral intrathecal immune response.
ABSTRACT
BACKGROUND: The determination of kappa free light chains (KFLC) in cerebrospinal fluid (CSF) is an upcoming biomarker for the detection of an intrathecal immunoglobulin synthesis. Since renal function impairment leads to altered serum KFLC and albumin concentrations, interpretation of KFLC in CSF may be influenced by these parameters. METHODS: In this two-center study, the influence of renal function (according to the CKD-EPI creatinine equation) on KFLC and albumin concentrations was investigated in patients with "physiological" (n = 139), "non-inflammatory" (n = 146), and "inflammatory" (n = 172) CSF profiles in respect to the KFLC index and the evaluation in quotient diagrams in reference to the hyperbolic reference range (KFLC IF). RESULTS: All sample groups displayed declining KFLC indices and KFLC IF values with decreasing renal function (P-values between <.0001 and .0209). In "inflammatory" CSF profile samples, 15% of the patients presented a KFLC index <5.9 while 10% showed an intrathecal KFLC fraction below QKappa(lim), suggesting possible false negative KFLC results. CONCLUSIONS: The influence of renal function should be considered while interpreting KFLC results in patients with neuroinflammatory diseases. The interpretation of KFLC in quotient diagrams is less susceptible to renal function impairment than the KFLC index and should be preferentially used.
ABSTRACT
BACKGROUND: This observational study was done to develop a score based on clinical predictors that enables a guided decision for the necessity of cerebrospinal fluid (CSF) analysis after first unprovoked epileptic seizures and to validate this score in a retrospective patient cohort. METHODS: Clinical predictors were identified by two panels of epilepsy experts and selected according to content validity ratios. Based on these predictors a score was created and applied to a cohort of patients with first epileptic seizures. RESULTS: The "IDEAL score" consists of 9 items (fever, prolonged disturbance of consciousness, headache, imaging results, cognitive dysfunction, status epilepticus, malignancy, autoimmune encephalitis symptoms) that are collected at two different time points (< 3 h [A-score]; > 3 h [B-score] after hospital admittance). A CSF analysis is recommended, if at least one clinical finding is present, either one of the items evaluated during the acute phase (A-score) or later in the diagnostic process (B-score). In 41 patients (13%) CSF analysis provided essential clues to the cause of the seizure. The combined IDEAL score reached a sensitivity of 98%, a specificity of 53%, a positive predictive value of 24% and a negative predictive value of 99% in this patient cohort. CONCLUSIONS: A CSF analysis after first epileptic seizures provided decisive etiological findings in only 13% of all investigated patients. The IDEAL score offers clinicians a simple and easy-to-implement algorithm to assess the necessity of a CSF analysis, and to prevent unnecessary diagnostic procedures.
