Diagnosis of neuroborreliosis – Improved knowledge base for qualified antibody analysis and cerebrospinal fluid data pattern related interpretations

Abstract

Recent guidelines do not specify inflammatory CSF pattern, ignore IgM analysis, use unsuitable cut offs and miss the polyspecific immune response for intrathecal antibody interpretation. Insufficient quality of antibody assays together with insensitive evaluations contribute to false positive and false negative interpretations.To improve diagnostic sensitivity and specificity antibody assays are analyzed with external quality assessment (INSTAND survey) and interpretation problems are documented by new CSF statistics. Patient groupsdefinite neuroborreliosis (N=29), multiple sclerosis (N=35), seropositives without neuroborreliosis (N=16) and seropositives with other neurological diseases (N=36). In acute neuroborreliosis intrathecal immunoglobulin classes IgG/IgA/IgM had a statistical frequency of 59%/41%/100% correspondingly. Predominant intrathecal IgM had a diagnostic sensitivity of 93% and the blood-CSF barrier dysfunction 86%. Sensitivity of Bb-antibodies was 100% (IgG) and 83% (IgM) by corrected borrelia-AI and cut off Bb-AI≥1.5. CSF pattern clearly discriminates borrelia- and VZV-caused facial nerve palsy. 47% of Bb-seropositive MS patients had an intrathecal Bb antibody synthesis. CSF Bb-antibodies without serum antibodies were not found (N=680). In the neuroborreliosis-survey among 150 participating laboratories we got 4–80% outliers (±30% success-interval) and method-dependent differences between median AI values of a factor three due to different antigen coating.Antigen coating and evaluation by corrected AI is crucial for sensitivity of antibody assays. Specificity depends on a complete CSF data pattern including IgM. The post lyme disease is discussed regarding deficits in analysis, wrong clinical diagnosis, or borrelia as an unspecific trigger of a chronic disease with a multitude of possible causes.