Abstract
BackgroundThe analysis of cerebrospinal fluid (CSF) is usually done under steady-state conditions, when proteins (e.g., immunoglobulins) reach diffusion equilibrium between blood and CSF. However, little data has been published on CSF analysis under non-steady-state conditions after therapeutic apheresis. By reducing serum proteins (e.g., immunoglobulins), while leaving CSF unchanged, therapeutic apheresis might cause spuriously altered intrathecal immunoglobulin fractions.MethodsBased on the incidental finding of plasma exchange-induced increased intrathecal immunoglobulin fractions in a cohort of 12 unsystematically selected patients with various neurological disorders, we retrospectively investigated CSF results that had been raised during routine diagnostic work-up from 41 consecutive neurological patients (predominantly Guillain-Barré syndrome and autoimmune encephalitis) treated with plasmapheresis or immunoadsorption in a tertiary care university hospital in whom lumbar puncture (LP) was performed after a varying number of treatments of therapeutic apheresis.ResultsOnly when LP was performed 1 day after therapeutic apheresis, spurious quantitative intrathecal immunoglobulin (Ig) synthesis of at least one subclass (IgG, IgA and/or IgM) was found in 68.4 % of the patients, irrespective of the number of treatments, in all age groups and independent of other previous immunotherapies (e.g., steroids). This phenomenon occurred only transiently and was almost always accompanied by an elevation of the IgG index. In one patient, an elevated IgG index was noticed even 2 days after plasmapheresis. Neither quantitative Ig synthesis, nor elevated IgG index was observed when the LP was performed three or more days after therapeutic apheresis.ConclusionsSpurious quantitative intrathecal Ig synthesis and increased IgG index are common findings shortly after plasmapheresis or immunoadsorption due to altered serum immunoglobulin levels. Knowledge of this phenomenon is needed for clinicians to prevent false interpretations leading to unnecessary diagnostic and therapeutic procedures. Misdiagnoses can be avoided by considering the characteristic CSF constellation including absence of oligoclonal bands and the close temporal relation to therapeutic apheresis.
Highlights
The analysis of cerebrospinal fluid (CSF) is usually done under steady-state conditions, when proteins reach diffusion equilibrium between blood and CSF
Analysis before PE without increased intrathecal immunoglobulin fractions. In these six patients lumbar puncture (LP) showing increased intrathecal Ig fractions was performed after a median number of three apheresis treatments
The relevance of our findings is further illustrated by the fact that the misinterpretation of spurious intrathecal Ig synthesis 1 day after therapeutic apheresis resulted in further specific diagnostics and/or unnecessary treatments in some of our patients
Summary
The analysis of cerebrospinal fluid (CSF) is usually done under steady-state conditions, when proteins (e.g., immunoglobulins) reach diffusion equilibrium between blood and CSF. In some inflammatory neurological disorders of infectious or autoimmune origin (e.g., neuroborreliosis, other viral and bacterial infections, and multiple sclerosis), the disturbance of immunoglobulin (Ig) and albumin quotients leads to an increase of the quantitatively calculated intrathecal Ig fractions indicative of an intrathecal antibody production by local B-cells. In this regard, intrathecal Ig synthesis strongly suggests a neuroinflammatory process [3]. During or shortly after therapeutic apheresis, a follow-up CSF analysis becomes necessary for various reasons (e.g., control of CSF cell count or pathogenic antibodies) in clinical routine
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