The analysis of cerebrospinal fluid (CSF) remains a valuable diagnostic tool in the evaluation of inflammatory and infectious conditions involving the brain, spinal cord, and meninges. Since many rheumatic inflammatory diseases can involve the central and peripheral nervous system, the aims of this narrative review were to summarize the latest evidence on the use of CSF analysis in the field of neuropsychiatric manifestations of rheumatic diseases. Routine CSF parameters were taken into consideration for this review: appearance; total protein and cellular content (pleocytosis); lactate and/or glucose; CSF/serum albumin quotient; intrathecal synthesis of IgG. Data regarding the role of CSF analysis in the clinical management of neuropsychiatric systemic lupus erythematosus, primary Sjogren’s syndrome, rheumatoid arthritis, and Behçet’s syndrome are presented. Although no disease-specific picture has been identified, CSF analysis remains a useful diagnostic tool to confirm the presence of a neuro-inflammatory state or, conversely, to exclude the concomitant presence of other inflammatory/infectious diseases affecting the CNS in the context of systemic rheumatologic conditions.

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.

(1) Background: The recent emphasis on sexual and gender diversity’s impact on human health underscores the need for tailored diagnostic and therapeutic approaches in neurology. The aim of this article is to conduct a narrative review of the available scientific literature on sex differences in cerebrospinal fluid analysis. (2) Methods: The literature search encompassed PubMed databases, focusing on cerebrospinal fluid analysis and sex differences, considering parameters like cerebrospinal fluid protein content, cell count, albumin quotient (QAlb) and intrathecal IgG synthesis. (3) Results: Nine articles from the past two decades were identified, revealing limited research in this area. Males consistently exhibited higher cerebrospinal fluid protein content and albumin quotient values across various pathologies and age groups. Consequently, males more frequently manifested blood–cerebrospinal fluid barrier dysfunction than females. No significant sex differences were observed in cerebrospinal fluid leukocyte count or intrathecal IgG synthesis. (4) Conclusions: This review highlights the dearth of research on sex differences in cerebrospinal fluid analysis, despite consistent findings of higher protein content and albumin quotient values in males. Revisiting current diagnostic thresholds based on sex is crucial for accurate prognosis and personalised treatment strategies in neurological disorders. Moving towards sex-specific approaches in clinical practice is imperative for advancing personalised medicine.

(1) Background: Cerebrospinal fluid (CSF)/serum albumin quotient (QAlb) and CSF total protein (TP) are more elevated in males than females, and this has been hypothesised to be due to anthropometric differences between the sexes. This study aimed to investigate QAlb and CSF TP as a function of body height, weight, and body mass index (BMI). (2) Methods: A total of 207 patients were included in the study and analysed blinded to clinical diagnosis. (3) Results: Multivariable linear regressions were run to predict log-transformed Qalb and log-transformed CSF TP value from age, sex, weight, and height (first model) or from age, sex, and BMI (second model). In both models, age (β = 0.004, 95% CI = 0.002 to 0.006) and sex (β = −0.095, 95% CI = −0.169 to −0.021, and β = −0.135, 95% CI = −0.191 to −0.079) were significant predictors for QAlb, but weight, height, and BMI were not. Similarly, age (β = 0.004, 95% CI = 0.003 to 0.006) and sex (β = −0.077, 95% CI = −0.142 to −0.013, and β = −0.109, 95% CI = −0.157 to −0.060) were significant predictors for CSF TP, while anthropometric characteristics were not. No differences in QAlb and CSF TP were found when grouping males and females by BMI status. (4) Conclusions: Our data suggest that anthropometric characteristics could not explain the sex-related differences in QAlb and CSF TP.

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/Objectives: Accurate measurement of total protein (TP) in cerebrospinal fluid (CSF) is crucial for diagnosing various neurological conditions. This study aims to evaluate the concordance between a routine colorimetric method and a recently introduced turbidimetric method for measuring CSF TP. Methods: We measured 161 CSF samples using both methods, analyzing the whole population and two subgroups: normal (≤500 mg/L) and pathological (>500 mg/L). Agreement was assessed using Lin’s Concordance Correlation Coefficient (CCC), Bland–Altman, and Deming regression, while clinical concordance was determined with Cohen’s Kappa. Results: The concentrations obtained from the two methods did not differ significantly and were well-correlated across the population and subgroups. The CCC for the entire dataset was 0.9881 (substantial agreement), while the Bland–Altman analysis showed a mean bias of 4.467 mg/L. For the “normal” subgroup (n = 97), the CCC was 0.8722 (poor agreement), with a mean bias of 7.668 mg/L. In the “pathological” subgroup (n = 64), the CCC was 0.9858 (substantial agreement) with a mean bias of −3.838 mg/L. Demin regression did not show statistically significant proportional or constant bias in the whole population. However, a stratified analysis revealed a significant negative constant bias in the “normal” subgroup in absence of significant bias in the “pathological” subgroup. Cohen’s kappa was 0.804, indicating substantial agreement. Conclusions: Both methods showed substantial agreement for quantifying CSF TP and clinical classification, supporting their potential interchangeability for diagnostic purposes. Nonetheless, laboratories should note the presence of bias, particularly for samples near the clinical cut-off value.