Breaking Barriers: Unveiling Sex-Related Differences in Cerebrospinal Fluid Analysis—A Narrative Review

Simple Summary In recent years, biomedical research has extensively explored gender and sex differences to achieve individualised care. These advancements are yielding new insights across various medical domains. Our review focuses on sex-related disparities in the field of neurological disorders, specifically examining differences observed in certain biomarkers routinely used in cerebrospinal fluid analysis for diagnostic purposes. Our bibliographical research initially indicates that a gender/sex-based approach to data analysis is still relatively uncommon in this field. However, our work highlights a strong consensus among studies thus far that male patients exhibit higher protein content compared to females, likely attributable to differing functionality of the structures responsible for isolating the central nervous system from the bloodstream. Our study aims to prompt the development of sex-specific guidelines for evaluating laboratory parameters of neurological interest, thereby mitigating the risk of overestimation in one sex and/or underestimation in the other. In the era of the search for cost-effective, personalised and precision medicine, these considerations could have a practical impact for the better management of patients with suspected neurological disorders.Abstract (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.