Abstract
The central role played by cerebrospinal-fluid (CSF) examinations including antineuronal autoantibody (Ab) testing is increasingly recognized in psychiatry. The rationale of this study was to present a multimodally investigated group of patients. In total, 992 patients were analyzed for CSF alterations: 456 patients with schizophreniform and 536 with affective syndromes. Ab measurement included testing for established antineuronal IgG-Abs against intracellular antigens in serum (Yo/Hu/Ri/cv2[CRMP5]/Ma1/Ma2/SOX1/TR[DNER]/Zic4/amphiphysin/GAD65) and for cell surface antigens in the CSF (NMDAR/AMPA-1/2-R/GABA-B-R/LGI1/CASPR2/DPPX). In 30 patients with “red flags” for autoimmune psychosis, “tissue tests” were performed. Additional diagnostics included MRI and EEG analyses. CSF white-blood-cell counts were increased in 4% and IgG indices in 2%; CSF-specific oligoclonal bands were detected in 4%; overall, 8% displayed signs of neuroinflammation. In addition, 18% revealed increased albumin quotients. Antineuronal Abs against intracellular antigens were detected in serum in 0.6%. Antineuronal Abs against established cell surface antigens were detected in serum of 1% and in the CSF of 0.3% (CSF samples were only questionably positive). Abnormal IgG binding in “tissue tests” was detected in serum of 23% and in CSF of 27%. In total, 92% of the Ab-positive patients demonstrated at least one sign of brain involvement in additional diagnostics using CSF, MRI, EEG, and FDG-PET. In summary, CSF basic analyses revealed signs of blood–brain-barrier dysfunction and neuroinflammation in relevant subgroups of patients. Established antineuronal IgG-Abs were rare in serum and even rarer in the CSF. “Tissue tests” revealed frequent occurrences of Ab-binding; therefore, novel antineuronal Abs could play a relevant role in psychiatry.
Highlights
In the last decade, the study of autoimmune encephalitis (AE) and autoimmune psychosis (AP) has rapidly developed[1,2], largely due to the discovery of anti-N-methylD-aspartate receptor (NMDAR) encephalitis in 2007
Since 2007, the importance of AE has increased in the field of psychiatry with the recognition that antiNMDAR encephalitis often manifests with psychotic symptoms and that these patients are usually seen initially by psychiatrists[4,5,6,7]
The aim of the present study was to conduct a retrospective evaluation of a large cohort of patients with schizophreniform and affective syndromes who underwent multimodal examinations consisting of cerebrospinal fluid (CSF) analyses, antineuronal Ab testing in serum/CSF, EEG, and magnetic resonance imaging (MRI)
Summary
The study of autoimmune encephalitis (AE) and autoimmune psychosis (AP) has rapidly developed[1,2], largely due to the discovery of anti-N-methylD-aspartate receptor (NMDAR) encephalitis in 2007. CSF diagnostics play a central role in the context of antineuronal Abs, since low antigen-specific immunoglobulin (Ig) G Ab titers can be detected even rarely in the serum of healthy individuals[11,12,13]. This finding emphasizes the necessity of evaluating the pathophysiological relevance of these Abs by CSF analyses[2,7,16]. According to recently published international consensus criteria for AP, a diagnosis of “probable AP” requires typical CSF, MRI, or EEG findings, while confirmation of a diagnosis of “definite AP” requires the detection of IgG antineuronal Abs in the CSF2
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