Role and Relevance of Cerebrospinal Fluid Cells in Diagnostics and Research: State-of-the-Art and Underutilized Opportunities

Cerebrospinal fluid (CSF) has recently experienced a revival in diagnostics and research. However, little progress has been made regarding CSF cell analysis. For almost a century, CSF cell count and cytomorphological examination have been central diagnostic parameters, with CSF pleocytosis as a hallmark finding of neuroinflammation and cytology offering valuable clues regarding infectious, autoimmune, and malignant aetiologies. A great deal of information, however, remains unattended as modern immune phenotyping technologies have not yet been broadly incorporated into routine CSF analysis. This is a serious deficit considering the central role of CSF cells as effectors in central nervous system (CNS) immune defence and autoimmune CNS processes, and the diagnostic challenges posed by clinically overlapping infectious and immune-mediated CNS diseases. Here, we summarize historical, specimen-intrinsic, methodological, and technical issues determining the state-of-the-art diagnostics of CSF cells and outline future perspectives for this underutilized window into meningeal and CNS immunity.

Automated summary

Cerebrospinal fluid (CSF) has seen a resurgence in diagnostics and research, but advancements in CSF cell analysis have been limited. While CSF cell count and cytology have been central in diagnosing CNS diseases, the lack of incorporation of modern immune phenotyping technologies has left valuable information unexplored. This gap is particularly concerning given the important role of CSF cells in CNS immune defense and autoimmune processes, as well as the diagnostic challenges posed by overlapping infectious and immune-mediated CNS diseases.