A modern approach to CSF analysis: pathophysiology, clinical application, proof of concept and laboratory reporting

Abstract

The CNS immune response often leads to characteristic interrelated biochemical changes in cerebrospinal fluid. Multiple analytes, i.e. cell count, cell differential, evaluation of barrier function and intrathecal IgG, IgA and IgM synthesis should be included in basic diagnostic workup. We describe the scientific background, laboratory investigations and characteristic patterns found with basic CSF analysis, based on the recommendations of the German cerebrospinal fluid society. The concept is substantiated by retrospectively analyzing data of 4026 paired CSF/serum samples. 53% of our samples presented with at least one or several combined abnormal findings. An intrathecal IgG, IgA or IgM immunoglobulin response (37%, n=1481) and a blood-CSF barrier dysfunction (37%; n=1473) were most frequent; followed by an elevated leukocyte cell count (25%; n=992). The immunoglobulin response showed an intrathecal production of IgG in 49% (n=731/1481), which was only detectable in isoelectric focusing in 27% (n=200/731). Intrathecal IgM (n=389) and IgA (n=361) synthesis presented with nearly equal frequency of 25% in samples with intrathecal immunoglobulin response. The immunoglobulin pattern showed a solitary one class reaction of IgG, IgA or IgM in 67%, a combined two class reaction of IgG/IgA, IgG/IgM or IgA/IgM synthesis in 16% and a combined three-class reaction of IgG, IgA and IgM in 17%. This approach generates valuable but numerous complex and interrelated biochemical data. We therefore developed a knowledge-based system combined with visual oriented laboratory output to transfer the information more effectively. This often uncovers typical patterns specific for distinct neurological diseases, is well accepted by our medical community documented by a 37% increase in external ordering.