Abstract
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.
Highlights
Cerebrospinal fluid (CSF) is a clear colourless liquid that surrounds the brain and spinal cord and plays a vital role in central nervous system (CNS) homeostasis [1]
In addition to specimen-intrinsic factors relating to the instability and paucity of CSF cells, clinical implementation of flow cytometry for CSF cells has suffered from: (i) low CSF collection volumes, (ii) lack of consensus protocols for preanalytics, processing, antibody panels, and gating strategies, and (iii) outsourcing of CSF diagnostics from specialized neuroimmunological to large central laboratories ob
In addition to specimen-intrinsic factors relating to the instability and paucity of CSF cells, clinical implementation of flow cytometry for CSF cells has suffered from: (i) low CSF collection volumes, (ii) lack of consensus protocols for preanalytics, processing, antibody panels, and gating strategies, and (iii) outsourcing of CSF diagnostics from specialized neuroimmunological to large central laboratories observable at least in German speaking European countries
Summary
Cerebrospinal fluid (CSF) is a clear colourless liquid that surrounds the brain and spinal cord and plays a vital role in central nervous system (CNS) homeostasis [1]. Cerebrospinal fluid is a highly important immune interface between the meninges, CNS, and periphery It steadily flows through the subarachnoid space in direct touch with resident dendritic cells and long-lived pial macrophages. While advances in laboratory techniques have broadened the indications and significance of CSF diagnostics by allowing investigating, for instance, an increasing repertoire of neuronal autoantibodies in suspected autoimmune encephalitis (AIE) and biomarkers of neurodegenerative diseases [20], little progress has been made regarding CSF cells This is astonishing considering their central role in CNS immune surveillance as effectors and drivers of CNS immune defence as well as autoimmune CNS processes, in particular humoral adaptive immune activities, such as intrathecal antibody synthesis [21]. Why is this so? Here, in the quest for an answer, we outline the historical and stateof-the art methods of investigating CSF cells for diagnostic purposes and summarize technologically available yet underutilized opportunities for enhancing our understanding of meningeal CNS immunity
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