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

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.

Effect of ampicillin-sulbactam on clinical capillary zone electrophoresis of serum proteins.

BACKGROUND: Capillary zone electrophoresis (CZE) is a well-accepted automated method used to separate serum proteins and detect monoclonal components. CZE uses ultraviolet detection at 214 nm to directly quantify proteins via peptide bonds. Any substance that absorbs at 214 nm and is present in serum can potentially interfere with CZE analysis. This has been reported for radio-contrast media and antibiotics. METHODS: Here we describe a peak on the anode side of the alpha(2)-globulin fraction caused by the antibiotic ampicillin-sulbactam (Unacid). RESULTS AND CONCLUSIONS: Extra peaks that can be misinterpreted as monoclonal components can be present in almost all electrophoretic fractions of CZE. Immunosubtraction or immunofixation is always required to rule out these conditions.