The K free light chain (K) index has been suggested as a reliable marker of intrathecal synthesis, despite the 2017 McDonald criteria for multiple sclerosis (MS) suggesting to “interpret with caution positive immunoglobulin G (IgG) index when testing for oligoclonal bands (OB) is negative or not performed”. The aim of this study was to compare the performance of K and IgG indexes for MS diagnosis and OB detection in a cohort of Italian patients. We enrolled 385 patients (127 MS, 258 non-MS) who had cerebrospinal fluid (CSF) analysis, including isoelectric focusing (IEF), to detect OB in the diagnostic work-up. Albumin, IgG and free light chains were measured by nephelometry and used to calculate IgG and K indexes. Although the two markers were highly related (r = 0.75, r² = 0.55, p < 0.0001), the K index showed greater sensitivity and negative predictive value (versus the IgG index) for OB detection (97% versus 48% and 97% versus 71%) and MS diagnosis (96% versus 50% and 98% versus 78%). These results support K index (and not IgG index) as a first-line marker for MS, followed by IEF, according to a sequential testing approach in CSF analysis.

Slowed information processing speed (IPS) is the hallmark and first cognitive domain to be altered in multiple sclerosis (MS) patients. Insufficient serum vitamin D was previously associated with disease development, relapses, and progression, but little is reported on cognition. However, vitamin D and cognitive impairment (CI) in other neurodegenerative diseases have already been linked. We explored the possible correlation between vitamin D and IPS at diagnosis and early disability at last follow-up in 81 MS patients. At diagnosis, we collected vitamin D levels and performed a Symbol Digit Modalities Test (SDMT). Raw scores were adjusted for age, gender, and educational level. Early disability was evaluated with MS severity score (MSSS) and age-related MSSS (ARMSS). A total of 71 patients (86.58%) showed hypovitaminosis D (19.71 ± 8.76 ng/mL) and 18 patients (21.95%) had CI. Patients with CI showed severe hypovitaminosis D (p = 0.004). No patients with sufficient vitamin D levels had CI. We found a positive correlation between vitamin D levels at diagnosis and (1) SDMT raw and z-score that persisted after correction for sunlight exposure and MRI baseline characteristics, and (2) EDSS, MSSS, and ARMSS after a mean 2 year follow-up. Low vitamin D levels may affect both cognition and early disability in newly diagnosed MS patients.

The kappa index (K-Index), calculated by dividing the cerebrospinal fluid (CSF)/serum kappa free light chain (KFLC) ratio by the CSF/serum albumin ratio, is gaining increasing interest as a marker of intrathecal immunoglobulin synthesis. However, data on inter-laboratory agreement of these measures is lacking. The aim was to assess the concordance of CSF and serum KFLC measurements, and of K-index values, across different laboratories. KFLC and albumin of 15 paired CSF and serum samples were analyzed by eight participating laboratories. Four centers used Binding Site instruments and assays (B), three used Siemens instruments and assays (S), and one center used a Siemens instrument with a Binding Site assay (mixed). Absolute individual agreement was calculated using a two-way mixed effects intraclass correlation coefficient (ICC). Cohen’s kappa coefficient (k) was used to measure agreement on positive (≥5.8) K-index values. There was an excellent agreement in CSF KFLC measurements across all laboratories (ICC (95% confidence interval): 0.93 (0.87–0.97)) and of serum KFLC across B and S laboratories (ICC: 0.91 (0.73–0.97)), while ICC decreased (to 0.81 (0.53–0.93)) when including the mixed laboratory in the analysis. Concordance for a positive K-Index was substantial across all laboratories (k = 0.77) and within S laboratories (k = 0.71), and very good (k = 0.89) within B laboratories, meaning that patients rarely get discordant results on K-index positivity notwithstanding the testing in different laboratories and the use of different platforms/assays.

Background: Kidney function in preterm newborns may be impaired by many factors. Methods: 71 newborns with gestational age (GA) < 32 weeks were enrolled. Serum creatinine (sCr), cystatin C (CysC), beta-trace protein (BTP) and urea were measured at T0 (3rd day of life) and T36 (GA 36 weeks), and estimated glomerular filtration rate (eGFR) was calculated according to different formulas at T36. Pre-natal and post-natal kidney injury risk scores were calculated. Results: Newborns with GA ≤ 28 weeks had higher sCr at T0, and lower sCr, BTP and higher urea levels at T36 (p = 0.007, p = 0.005 and p = 0.029, respectively). eGFR values were not different according to GA when calculated by the formulas using only CysC, but were higher in subjects with GA ≤ 28 weeks according to the other formulas. The post-natal score was positively correlated with eGFR according to sCr-based formulas, but the correlations did not persist when adjusted for urea levels and GA. Conclusions: CysC-based eGFR values are not influenced by GA. Post-natal score shows a direct correlation with eGFR according to sCr-based formulas, not persisting after adjustment for GA and urea levels, implying the importance of the nutritional status, since more premature subjects receive a more aggressive nutritional regimen, testified by higher urea levels.