Cerebrospinal fluid, antineuronal autoantibody, EEG, and MRI findings from 992 patients with schizophreniform and affective psychosis

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.

Immunotherapy in Autoantibody-Associated Psychiatric Syndromes in Adults

“…In line with the aforementioned studies ( 19 , 23 ), we recommend immunotherapy ( Figure 1 and Table 1 ) for patients presenting probable or definitive autoimmune-based psychiatric syndromes according to this therapeutic pathway ( Figure 1 and Table 1 ): first-line immunotherapy should include steroids (i.v. or oral), IVIGs, immunoadsorption and/or PLEX.…”

“…Thirteen of 24 antibody-positive patients in this large cohort received immunotherapy, and 87% exhibited a good response to immunotherapy which had azathioprine, methotrexate, mycofenolat mofetil, and rituximab. Taken together, these large observational studies ( 19 , 23 ) deliver a low, but consistent evidence level that in those patients with psychiatric syndromes and proven autoantibodies, immunotherapy succeeded in 87–94% of patients ( n = 139). The evidence from these large retrospective case studies supports the usefulness of immunotherapy ( Table 1 ).…”

“…Immunotherapy was more beneficial in those patients with autoantibody-associated psychiatric syndromes who presented with autoantibodies against membrane-surface antigens [77 of 80 patients (88%)] compared to those with autoantibodies against intracellular antigens [6/15 patients (40%)] ( 19 ) resembling the findings on patients with autoimmune encephalitis ( 20 – 22 ). Another large cohort study from the same working group ( 23 ) investigated the occurrence of autoantibody-associated psychiatric disease in patients with schizophrenic and affective psychosis. Thirteen of 24 antibody-positive patients in this large cohort received immunotherapy, and 87% exhibited a good response to immunotherapy which had azathioprine, methotrexate, mycofenolat mofetil, and rituximab.…”

Upregulation of sICAM-1 and sVCAM-1 Levels in the Cerebrospinal Fluid of Patients with Schizophrenia Spectrum Disorders

“…The routine CSF analysis included the determination of white blood cell (WBC) count, protein concentration, AQ, immunoglobulin (Ig)G index, and oligoclonal bands (OCBs) according to an established methodology (c.f. Endres et al, 2015Endres et al, , 2020. The measurements were carried out in the CSF laboratory of the University Hospital Freiburg (https://www.uniklinikfreiburg.de/neurologie/klinik/diagnostische-einrichtungen/liquor-labor.html).…”

“…Schizophrenia spectrum disorders were interpreted by several authors as complex neuropsychiatric disorders involving an activated in ammatory response leading to mild neuroin ammation (Bechter, 2013;Muller, 2019;Müller et al, 2013;Nguyen et al, 2018;Stefanovic et al, 2016). In this context, the functions of the blood-brain barrier (BBB) and the blood-cerebrospinal uid (CSF) barrier (BCSFB) play a central role (Pollak et al, 2018), and a number of clinical studies showed alterations in biomarkers associated with the BBB/BCSFB (Endres et al, 2020;Endres et al, 2015;Najjar et al, 2017;Najjar et al, 2013;Orlovska-Waast et al, 2019). The central nervous system (CNS) is surrounded by the dynamic and metabolically active CSF and is separated from the peripheral circulation by several barriers, the most prominent are the BBB and the BCSFB (Banks et al, 2010;Deisenhammer et al, 2006;Tumani et al, 2017;Wildemann et al, 2010).…”