Michele Laudisi

Background: The triglyceride glucose index (TyG-i), a biomarker of insulin resistance, has been associated with adverse vascular outcomes and risk stratification in several cardiovascular and cerebrovascular phenotypes. However, data on TyG-i as a prognostic marker in spontaneous intracerebral hemorrhage (ICH) remain limited. Objective: To explore the association between TyG-i and 90-day functional outcome in patients with ICH. Methods: A retrospective analysis of adult patients admitted for non-traumatic small vessel disease-related ICH at three Italian neurological institutions was conducted. TyG-i was calculated on admission as Ln[(fast triglycerides (mg/dL) × fast glucose (mg/dL))]/2. Functional outcome was measured with the modified Rankin Scale (mRS) at 90 days from the index event. TyG-i was analyzed as a continuous variable and categorized in quintiles (Q1 to Q5). Predictors of poor outcome (mRS 4–6) were investigated with multivariable logistic regression. Results: A total of 463 patients were included, of whom 197 (42.5%) had poor outcome at 90 days. TyG-i analyzed as a continuous variable was not associated with unfavorable prognosis. TyG-i analyzed as a categorical variable stratified by quintiles showed a non-linear U-shaped relationship with functional outcome; patients in Q4 had the lowest risk of poor outcome (Q1 reference, OR 0.44, 95% CI 0.22–0.87, p = 0.019). Discussion: We found a potential non-linear relationship between TyG-i and ICH outcome, with higher odds of good prognosis in patients with intermediate values. Conclusions: TyG-i may represent a promising, low-cost and widely available biomarker that might improve prognostication in clinical practice, but further studies are needed.

Background Kappa free light chains (KFLC) in cerebrospinal fluid (CSF) have emerged as quantitative biomarkers of intrathecal humoral immune activity and are now included in diagnostic criteria for multiple sclerosis (MS). The aim of this study was to evaluate the relationship between quantitative and qualitative KFLC parameters and intrathecal immunoglobulin synthesis in MS. Methods In this retrospective monocentric study, paired CSF and serum samples from 242 neurological patients, 171 with MS, were analyzed. KFLC, IgG and IgM concentrations were measured by turbidimetry and intrathecal synthesis was assessed using established linear and nonlinear indices. IgG and KFLC oligoclonal bands (OCB) were detected by isoelectric focusing followed by immunoblotting. Alternative K-index thresholds were explored and the independent contribution of IgG and IgM intrathecal fractions was assessed using multivariable regression models. Results K-index positivity showed a strong association with intrathecal IgG synthesis and IgG OCB in MS patients (all p < 0.0001) and was independent of age and sex. Multivariable analysis demonstrated that the K-index was independently associated with IgG (p < 0.0001), but not IgM (p = 0.738) intrathecal synthesis. Qualitative KFLC oligoclonality was frequently observed in patients with IgG OCB (89.19%). Conclusions KFLC are confirmed as a valuable complementary biomarker to IgG OCB in MS. K-index values should be evaluated in conjunction with clinical features, imaging data, and ongoing or prior treatments, as KFLC levels may be dynamic and treatment sensitive, with a potential risk of misclassification in diagnostically borderline cases.

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) are a hallmark of MS and reflect intrathecal IgG synthesis and inflammation. This study aims to analyze the temporal distribution of IgG OCBs in the CSF of patients with a definitive diagnosis of MS. Methods: This retrospective study included 500 patients with diagnosed MS. Patients were divided into four groups according to diagnostic epochs: Group 1 (Pre-2001 or Pre-McDonald), Group 2 (2001–2010 or McDonald 2001-Polman 2010), Group 3 (2010–2018 or Polman 2010), and Group 4 (Post-2018 or Thompson 2017). Statistical analyses examined temporal and sex differences in OCB positivity rates. Results: OCB positivity was lower in Group 4 (69.2%) compared to Group 1 (85.4%) in the overall population (p = 0.0022). A decrease in OCB positivity was observed in Groups 3 (62.5%) and 4 (71.8%) compared to Group 1 (92.5%) among males (p = 0.0117 and p = 0.0198, respectively) and in Group 4 (68.1%) compared to Group 1 (82.5%) among females (p = 0.0274). Conclusions: The present study provides valuable insights into temporal trends in CSF positivity among patients diagnosed with MS. There was an overall decrease in OCB positivity rates over the years, particularly in the post-2018 period.

Background: Kappa free light chains (KFLCs) are emerging as promising biomarkers for intrathecal B cell activity for diagnosing multiple sclerosis (MS) through cerebrospinal fluid (CSF) analysis. In this study, we evaluated the ability of KFLC formulas to identify the presence of MS and their agreement with the ‘gold standard’ of CSF IgG oligoclonal bands (OCBs). Methods: A total of 233 patients were included in this study: 149, comprising 43 males and 106 females, had MS, and the remainder, 40 males and 44 females, had other neurological diseases (ONDs). We evaluated the potential of KFLCs in terms of sensitivity, specificity, and accordance. All analyses were conducted using a sex-disaggregated approach. Results: KFLCs showed a high sensitivity for both sexes with respect to the diagnosis of MS, with values between 74.42% and 93.03%. The specificity of the various formulas was much lower for females when compared to males, with values between 45.45% and 59.09%, with a significant difference between the two sexes for the K Index > 5.9 (p = 0.0451). Cohen’s kappa showed substantial agreement for men and moderate agreement for women between the KFLC indices and OCB. Conclusions: This study highlights the potential of KFLCs as a biomarker for MS but emphasises the need for sex-specific thresholds to improve diagnostic accuracy.