Background Autoimmune encephalitis (AE) might be seropositive or seronegative, depending on whether antibodies targeting well-characterized neuronal antigens can be detected or not. Since data on treatment efficacy in seronegative cases, are scarce, the main rationale of this study was to evaluate immunotherapy response in seronegative AE in comparison to seropositive cases. Methods An electronic database search retrospectively identified 150 AE patients, treated in our tertiary care university hospital between 2010 and 2020 with an AE. Therapy response was measured using both general impression and the modified Rankin Scale (mRS). Results Seventy-four AE patients (49.3%) were seronegative and 76 (50.7%) seropositive. These cases were followed up for a mean of 15.3 (standard deviation, SD, 24.9) and 24.3 months (SD 28.1), respectively. Both groups were largely similar on the basis of numerous clinical and paraclinical findings including cerebrospinal fluid, electroencephalography, magnetic resonance imaging, and 18-F-fluor-desoxy-glucose-positron-emmission-tomography pathologies. The majority of patients (80.4%) received at least one immunotherapy, which were glucocorticoids in most cases (76.4%). Therapy response on general impression was high with 49 (92.5%) of treated seronegative, and 57 (86.4%) of treated seropositive AE cases showing improvement following immunotherapies and not significantly different between both groups. Notably, the proportion of patients with a favorable neurological deficit (mRS 0-2) was twice as high during long-term follow-up as compared to baseline in both groups. Conclusion Since both, patients with seronegative and seropositive AE, substantially benefitted from immunotherapies, these should be considered in AE patients irrespective of their antibody results.

Patients with myasthenia gravis (MG) are potentially prone for a severe COVID-19 course, but there are limited real-world data available on the risk associated with COVID-19 for patients with MG. Here, we investigate whether current immunosuppressive therapy (IST) influences the risk of SARS-CoV-2 infection and COVID-19 severity. Data from the German myasthenia gravis registry were analyzed from May 2020 until June 2021 and included patient demographics, MG disease duration, comorbidities, current IST use, COVID-19 characteristics, and outcomes. Propensity score matching was employed to match MG patients with IST to those without, and multivariable binary logistic regression models were used to determine associations between IST with (1) symptomatic SARS-CoV-2 infection and (2) severe COVID-19 course, as measured by hospitalization or death. Of 1379 patients with MG, 95 (7%) patients (mean age 58 (standard deviation [SD] 18) presented with COVID-19, of which 76 (80%) received IST at time of infection. 32 patients (34%) were hospitalized due to COVID-19; a total of 11 patients (12%) died. IST was a risk factor for hospitalization or death in the group of COVID-19-affected MG patients (odds ratio [OR] 3.04, 95% confidence interval [CI] = 1.02–9.06, p = 0.046), but current IST was not associated with a higher risk for SARS-CoV-2 infection itself. In this national MG cohort study, current IST use was a risk factor for a severe disease course of COVID-19 but not for SARS-CoV-2 infection itself. These data support the consequent implementation of effective strategies to prevent COVID-19 in this high-risk group. German clinical trial registry ( https://www.drks.de ), DRKS00024099, first patient enrolled: February 4th, 2019.

Autoimmune-mediated obsessive-compulsive disorder (OCD) during childhood has long been established in the context of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection ( 1 Swedo S.E. Leonard H.L. Mittleman B.B. Allen A.J. Rapoport J.L. Dow S.P. et al. Identification of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections by a marker associated with rheumatic fever. Am J Psychiatry. 1997; 154: 110-112 Crossref PubMed Google Scholar ). In adult psychiatry, the topic has increasingly gained interest in light of new developments regarding autoimmune encephalitis and autoimmune psychosis ( 2 Prüss H. Autoantibodies in neurological disease. Nat Rev Immunol. 2021; 21: 798-813 Crossref PubMed Scopus (86) Google Scholar , 3 Pollak T.A. Lennox B.R. Müller S. Benros M.E. Prüss H. Tebartz van Elst L. et al. Autoimmune psychosis: An international consensus on an approach to the diagnosis and management of psychosis of suspected autoimmune origin. Lancet Psychiatry. 2020; 7: 93-108 Abstract Full Text Full Text PDF PubMed Scopus (190) Google Scholar ). Hence, diagnostic criteria for autoimmune OCD in adulthood have been proposed recently, and the first respective cases were reported ( 4 Endres D. Pollak T.A. Bechter K. Denzel D. Pitsch K. Nickel K. et al. Immunological causes of obsessive-compulsive disorder: Is it time for the concept of an "autoimmune OCD" subtype?. Transl Psychiatry. 2022; 12: 5 Crossref PubMed Scopus (22) Google Scholar , 5 Endres D. Mertens L. Berger B. Reisert M. Runge K. Nickel K. et al. Autoimmune obsessive-compulsive disorder with novel anti-basal ganglia antibodies. Psychother Psychosom. 2022; 91: 214-216 Crossref PubMed Scopus (8) Google Scholar ). For the detection of neuroinflammatory processes, cerebrospinal fluid (CSF) analysis (besides the far more invasive brain biopsy) is considered the most sensitive diagnostic tool ( 6 Pankratz B. von Zedtwitz K. Runge K. Denzel D. Nickel K. Schlump A. et al. Cerebrospinal fluid findings in adult patients. World J Biol Psychiatry. 2023; 24: 292-302 Crossref Scopus (4) Google Scholar ). Here, we present 2 paradigmatic OCD patients with inflammatory CSF signals including antinuclear antibody staining in CSF and magnetic resonance imaging (MRI)/electroencephalography (EEG) findings compatible with OCD.

Objective Myasthenia gravis (MG) is the most common autoimmune disorder affecting the neuromuscular junction. However, evidence shaping treatment decisions, particularly for treatment-refractory cases, is sparse. Both rituximab and eculizumab may be considered as therapeutic options for refractory MG after insufficient symptom control by standard immunosuppressive therapies. Methods In this retrospective observational study, we included 57 rituximab-treated and 20 eculizumab-treated patients with MG to compare the efficacy of treatment agents in generalised, therapy-refractory anti-acetylcholine receptor antibody (anti-AChR-ab)-mediated MG with an observation period of 24 months. Change in the quantitative myasthenia gravis (QMG) score was defined as the primary outcome parameter. Differences between groups were determined in an optimal full propensity score matching model. Results Both groups were comparable in terms of clinical and demographic characteristics. Eculizumab was associated with a better outcome compared with rituximab, as measured by the change of the QMG score at 12 and 24 months of treatment. Minimal manifestation of disease was more frequently achieved in eculizumab-treated patients than rituximab-treated patients at 12 and 24 months after baseline. However, the risk of myasthenic crisis (MC) was not ameliorated in either group. Interpretation This retrospective, observational study provides the first real-world evidence supporting the use of eculizumab for the treatment of refractory, anti-AChR-ab positive MG. Nonetheless, the risk of MC remained high and prompts the need for intensified monitoring and further research effort aimed at this vulnerable patient cohort.

Introduction: Autoimmune obsessive-compulsive disorder (OCD) in the context of pediatric autoimmune neuro-psychiatric disorder associated with streptococcal infections (PANDAS) has been observed for decades. The first cases of autoimmune OCD in adulthood were recently described. An association between obsessive-compulsive symptoms (OCS) and systemic autoimmune diseases in the form of connective tissue disease has also been re-ported. However, whether an association exists between OCD and sarcoidosis is unknown.Case study: Here, the authors present an end 20-year-old female patient with symptoms of OCD in whom an advanced diagnostic work-up revealed inflammatory cerebrospinal fluid (CSF) changes (elevated IgG index, CSF-specific oligoclonal bands, intrathecal IgG synthesis, and a positive MRZ reaction). In tissue-based assays using unfixed mouse brain sections, both serum and CSF showed a distinct antinuclear antibody pattern with peri-nuclear staining. Electroencephalography identified frontocentral theta spindles. Upon endobronchial-guided lymph node biopsy demonstrating non-caseating lymph nodes in further work-up, sarcoidosis was diagnosed. Levels of the sarcoidosis parameters IL-2-R and neopterin were increased. Under immunotherapy for sarcoidosis, the OCS seemed to improve.Discussion: This case study is paradigmatic, as an association between sarcoidosis and OCD has not been pre-viously reported. After exclusion of alternative causes, the inflammatory CSF changes would be compatible with an inflammatory brain involvement of sarcoidosis. Autoimmune OCD may occur more frequently than is thought, probably also in the context of neurosarcoidosis. This could open up new opportunities through immunother-apies in rare cases with OCD.

Myasthenia gravis (MG) is a rare, long‐term autoimmune disorder that causes muscle weakness; the condition typically has phases when it remits and phases when it relapses. Even though treatment response with regards to immunosuppressive therapies in MG patients is classically monitored by clinical scores, identification of a serological biomarker that monitors treatment response could be helpful. Here, the authors explore the correlation between acetylcholine receptor (AChR) antibody titers with changes in clinical severity in patients with MG and discuss the implications for clinical practice.

BACKGROUND: Autoimmune psychosis may be caused by well-characterized anti-neuronal autoantibodies, such as those against the NMDA receptor. However, the presence of additional anti-central nervous system (CNS) autoantibodies in these patients has not been systematically assessed. METHODS: Serum and cerebrospinal fluid (CSF) from patients with schizophreniform and affective syndromes were analyzed for immunoglobulin G anti-CNS autoantibodies using tissue-based assays with indirect immunofluorescence on unfixed murine brain tissue as part of an extended routine clinical practice. After an initial assessment of patients with red flags for autoimmune psychosis (n = 30), tissue-based testing was extended to a routine procedure (n = 89). RESULTS: Based on the findings from all 119 patients, anti-CNS immunoglobulin G autoantibodies against brain tissue were detected in 18% (n = 22) of patients (serum 9%, CSF 18%) following five principal patterns: 1) against vascular structures, most likely endothelial cells (serum 3%, CSF 8%); 2) against granule cells in the cerebellum and/or hippocampus (serum 4%, CSF 6%); 3) against myelinated fibers (serum 2%, CSF 2%); 4) against cerebellar Purkinje cells (serum 0%, CSF 2%); and 5) against astrocytes (serum 1%, CSF 1%). The patients with novel anti-CNS autoantibodies showed increased albumin quotients (p =.026) and white matter changes (p =.020) more frequently than those who tested negative for autoantibodies. CONCLUSIONS: The study demonstrates five novel autoantibody-binding patterns on brain tissue of patients with schizophreniform and affective syndromes. CSF yielded positive findings more frequently than serum analysis. The frequency and spectrum of autoantibodies in these patient groups may be broader than previously thought.

BACKGROUND:Myasthenic crisis (MC) requiring mechanical ventilation (MV) is a rare and serious complication of myasthenia gravis. Here we analyzed the frequency of performed tracheostomies, risk factors correlating with a tracheostomy, as well as the impact of an early tracheostomy on ventilation time and ICU length of stay (LOS) in MC.METHODS:Retrospective chart review on patients treated for MC in 12 German neurological departments between 2006 and 2015 to assess demographic/diagnostic data, rates and timing of tracheostomy and outcome.RESULTS:In 107 out of 215 MC (49.8%), a tracheostomy was performed. Patients without tracheostomy were more likely to have an early-onset myasthenia gravis (27 [25.2%] vs 12 [11.5%], p = 0.01). Patients receiving a tracheostomy, however, were more frequently suffering from multiple comorbidities (20 [18.7%] vs 9 [8.3%], p = 0.03) and also the ventilation time (34.4 days ± 27.7 versus 7.9 ± 7.8, p < 0.0001) and ICU-LOS (34.8 days ± 25.5 versus 12.1 ± 8.0, p < 0.0001) was significantly longer than in non-tracheostomized patients. Demographics and characteristics of the course of the disease up to the crisis were not significantly different between patients with an early (within 10 days) compared to a late tracheostomy. However, an early tracheostomy correlated with a shorter duration of MV at ICU (26.2 days ± 18.1 versus 42.0 ± 33.1, p = 0.006), and ICU-LOS (26.2 days ± 14.6 versus 42.3 ± 33.0, p = 0.003).CONCLUSION:Half of the ventilated patients with MC required a tracheostomy. Poorer health condition before the crisis and late-onset MG were associated with a tracheostomy. An early tracheostomy (≤ day 10), however, was associated with a shorter duration of MV and ICU-LOS by 2 weeks.

Abstract Background Myasthenic crisis (MC) and disease exacerbation in myasthenia gravis (MG) are associated with significant lethality and continue to impose a high disease burden on affected patients. Therefore, we sought to determine potential predictors for MC and exacerbation as well as to identify factors affecting outcome. Methods We examined a retrospective, observational cohort study of patients diagnosed with MG between 2000 and 2021 with a mean follow-up of 62.6 months after diagnosis from eight tertiary hospitals in Germany. A multivariate Cox regression model with follow-up duration as the time variable was used to determine independent risk factors for MC and disease exacerbation. Results 815 patients diagnosed with MG according to national guidelines were included. Disease severity at diagnosis (quantitative MG score or Myasthenia Gravis Foundation of America class), the presence of thymoma and anti-muscle specific tyrosine kinase-antibodies were independent predictors of MC or disease exacerbation. Patients with minimal manifestation status 12 months after diagnosis had a lower risk of MC and disease exacerbation than those without. The timespan between diagnosis and the start of immunosuppressive therapy did not affect risk. Patients with a worse outcome of MC were older, had higher MGFA class before MC and at admission, and had lower vital capacity before and at admission. The number of comorbidities, requirement for intubation, prolonged mechanical ventilation, and MC triggered by infection were associated with worse outcome. No differences between outcomes were observed comparing treatments with IVIG (intravenous immunoglobulin) vs. plasma exchange vs. IVIG together with plasma exchange. Conclusions MC and disease exacerbations inflict a substantial burden of disease on MG patients. Disease severity at diagnosis and antibody status predicted the occurrence of MC and disease exacerbation. Intensified monitoring with emphasis on the prevention of infectious complications could be of value to prevent uncontrolled disease in MG patients. Graphical Abstract

Myasthenic crisis (MC) is a life-threatening condition for patients with myasthenia gravis (MG). Seronegative patients represent around 10–15% of MG, but data on outcome of seronegative MCs are lacking. We performed a subgroup analysis of patients who presented with MC with either acetylcholine-receptor-antibody-positive MG (AChR-MG) or seronegative MG between 2006 and 2015 in a retrospective German multicenter study. We identified 15 seronegative MG patients with 17 MCs and 142 AChR-MG with 159 MCs. Seronegative MCs were younger (54.3 ± 14.5 vs 66.5 ± 16.3 years; p = 0.0037), had a higher rate of thymus hyperplasia (29.4% vs 3.1%; p = 0.0009), and were more likely to be female (58.8% vs 37.7%; p = 0.12) compared to AChR-MCs. Time between diagnosis of MG and MC was significantly longer in seronegative patients (8.2 ± 7.6 vs 3.1 ± 4.4 years; p < 0.0001). We found no differences in duration of mechanical ventilation (16.2 ± 15.8 vs 16.5 ± 15.9 days; p = 0.94) and length of stay at intensive care unit (17.6 ± 15.2 vs 17.8 ± 15.4 days; p = 0.96), or in-hospital mortality (11.8% vs. 10.1%; p = 0.69). We conclude that MC in seronegative MG affects younger patients after a longer period of disease, but that crisis treatment efficacy and outcome do not differ compared to AChR-MCs.

Autoimmune obsessive–compulsive disorder (OCD) is rare. The case presented here is that of a female patient in her mid-thirties who developed postpartum OCD. Magnetic resonance imaging showed multiple juxtacortical hyperintensities that may have been post-inflammatory in origin. In tissue-based assays using mouse brain slices, the patient’s cerebrospinal fluid (CSF) showed novel anti-nucleoli autoantibodies in cerebellar Purkinje cells and cortical neurons. The CSF dopamine and glutamate concentrations were dysregulated. The clinical course and diagnostic findings were compatible with possible autoimmune OCD with postpartum onset.

aDepartment of Psychiatry and Psychotherapy, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; bClinic of Neurology and Neurophysiology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; cDepartment for Neurology, Helios Clinic Pforzheim, Pforzheim, Germany; dDepartment of Diagnostic and Interventional Radiology, Medical Physics, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; eDepartment of Stereotactic and Functional Neurosurgery, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburgy, Freiburg, Germany; fCenter for Basics in Neuromodulation, Faculty of Medicine, University of Freiburg, Freiburg, Germany; gDepartment of Neuroradiology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; hDepartment of Rheumatology and Clinical Immunology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; iDepartment of Neurology and Experimental Neurology, Charité – Universitätsmedizin Berlin, Berlin, Germany; jGerman Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany Received: December 3, 2021 Accepted: January 20, 2022 Published online: March 21, 2022

Objectives There is an emerging role of autoimmune causes related to severe mental disorders (SMD). The clinical approach in patients with chronic SMD and novel anti-central nervous system antibodies is complex.Methods Two corresponding cumulative cases are presented. Cerebrospinal fluid (CSF) and serum were investigated using tissue-based assays.Results Both patients suffered from chronic SMD and were negative for well-characterized neuronal antibodies. Patient 1 suffered from a dysexecutive and neurocognitive syndrome with mild abnormalities in automated electroencephalography analysis, elevated CSF protein levels, several serum autoantibodies (including antibodies against endothelial cells), and novel antibodies with a “dotted/scalloped” binding against cytoplasmic structures in CSF. Patient 2 with obsessive-compulsive disorder had left temporal abnormalities on automated magnetic resonance imaging analysis, an elevated CSF/serum albumin quotient, and novel atypical cytoplasmic “spotted” antibody staining in the serum. Patient 1 improved with immunotherapy using high-dose steroids, but patient 2 did not improve under the same treatment.Conclusions The detection of autoantibodies in CSF of chronic SMD may be beneficial in selecting some patients for immunotherapy. The possible impact of novel anti-cytoplasmic antibodies in this context is critically discussed. Further research is needed to establish the underlying pathophysiological processes as well as their diagnostic and therapeutic implications.

A recent publication by del Campo and colleagues (2022) summarized the current evidence of cerebrospinal fluid (CSF) biomarkers in frontotemporal dementia (FTD).1 In addition to the established CSF biomarkers of neurodegeneration,1 autoimmune mechanisms could be associated with FTD.2,3 Underlying autoimmune encephalitis or autoimmune psychosis can be treated with immunotherapies.3,4 The present article illustrates a paradigmatic case study in which routine diagnostic findings revealed the presence of neurodegenerative FTD5 and novel neuronal autoantibodies leading to the conclusion of possibly autoimmune-modulated neurodegenerative FTD. The 57-year-old male developed cognitive deficits, including substantial memory impairment, over 5 months, followed by a first acute severe psychotic decompensation, including auditory hallucinations, disorganized thinking, and suicidality due to the stress of hearing his own thoughts. His productive psychotic symptomatology regressed under treatment with aripiprazole (15 mg). Mirtazapine (30 mg) led to normalization of his sleep disturbances. However, the patient still suffered from concentration deficits, memory problems, anxiety, flat affect, and reduced energy levels. Neuropsychological testing revealed deficits in reaction time with or without sound and deficits in verbal learning andmemory abilities. Further diagnostic work-up resulted in findings reminiscent of neurodegenerative FTD. Magnetic resonance imaging (MRI) demonstrated right-sided anterior temporal lobe atrophy. [18F]Fluorodeoxyglucose positron emission tomography (FDG-PET) of the brain revealed right-ward asymmetric temporal polar hypometabolism compatible with right temporal variant of FTD (rtvFTD).6 CSF showed blood–CSF barrier disturbance and tauopathy. All well-characterized neuronal autoantibodies were negative. However, in tissue-based assays,7 a strong autoantibody staining against axon initial segments (AIS) was identified in the CSF (+++) and also weaker in serum. Thebinding patternwas reminiscent of anti-tripartite motif-containing protein 46 (TRIM46) autoantibodies, a marker of paraneoplastic neurological syndromes.8 However, testing for TRIM46 autoantibodies remained negative using a cell-based assay. Therefore, novel autoantibodies against another AIS antigen can be assumed to exist. After a multidisciplinary case discussion, immunotherapy with plasmapheresis (five sessions across 5 days) followed by azathioprine (up to 150 mg per day) was initiated. After plasmapheresis, mood and concentration improved (the patient felt “more receptive”), and anxi-

BACKGROUND AND PURPOSE:Acute hepatitis E virus (HEV) infections have been associated with various neurological disorders, including individual cases with Bell's palsy. Nonetheless, systematic studies in the latter are lacking. Therefore, this retrospective study systematically screened a cohort of patients with Bell's palsy for an acute HEV infection.METHODS:Overall, 104 patients with Bell's palsy treated in our clinic between 2008 and 2018 were identified. Serum samples were analyzed for anti-HEV immunoglobulin (Ig)M and IgG antibodies by enzyme-linked immunosorbent assay. Additionally, serum samples were tested for HEV RNA by polymerase chain reaction in 92 of these 104 patients presenting within the first 7 days from symptom onset. A large group of 263 healthy individuals served as controls.RESULTS:None of the patients with Bell's palsy but two healthy controls (0.8%) had an acute HEV infection. Anti-HEV IgG seroprevalence indicating previous infection was unexpectedly high in patients with Bell's palsy (34%) and revealed an age-dependent increase.CONCLUSIONS:In this first systematic study, no cases of Bell's palsy in association with an acute HEV infection were identified. However, based on previous case descriptions, rare associations cannot be excluded. Therefore, large prospective multicenter studies will be necessary for conclusions that are more definitive.

Introduction: The role of immunological mechanisms in the pathophysiology of mental disorders has been discussed with increasing frequency. In this context, especially schizophrenia has become the focus of attention after the discovery of autoimmune encephalitis, which might present with psychotic symptoms. Furthermore, multiple studies have identified associations between infections or autoimmune diseases and schizophreniform disorders. Cerebrospinal fluid (CSF) analysis plays a central role in identifying potential inflammatory processes in the central nervous system. Therefore, the rationale of this retrospective study was the analysis of different cytokines, including interleukin-8 (IL-8) levels, in the CSF of patients with schizophrenia spectrum disorders. Methods: The authors examined the CSF of 40 patients with schizophrenia spectrum disorders, in comparison to the CSF of a mentally healthy control group of 39 patients with idiopathic intracranial hypertension (IIH). Magnetic bead multiplexing immunoassay was used to retrospectively determine different cytokines in the participants' CSF. Results: Participants with schizophrenia spectrum disorders had significantly higher IL-8 levels in their CSF than controls (mean +/- SD: 41.83 +/- 17.50 pg/ml versus 21.40 +/- 7.96 pg/ml; p < 0.001). Conclusion: The main finding of this study is the presence of significantly higher IL-8 concentrations in the CSF of patients with schizophrenia spectrum disorders when compared to the control group. This supports the hypothesis that immunological processes may be involved in the pathophysiology of a subgroup of patients with schizophrenia spectrum disorders. However, the study's results are limited by the retrospective design, methodological aspects, and the control group with IIH. (c) 2021 Elsevier B.V. All rights reserved.

Background: Neuralgic amyotrophy (NA) has been described as a possible extrahepatic manifestation of hepatitis E virus (HEV) infection. Usually, HEV-associated NA occurs bilaterally. The clinical characteristics determining the course of HEV-associated NA have still not been defined. Methods: In this retrospective multicentric case series, 16 patients with HEV-associated NA were studied and compared to 176 HEV patients without NA in terms of their age, sex, and ALT levels. Results: Neither gender distribution (75% vs. 67% male) nor age (47 vs. 48 years median) differed significantly between the NA patients and controls. Eight NA patients (50%) presented with bilateral involvement-seven of these had right-side dominance and one had left-side dominance. Thirteen cases (81%) were hospitalized. Eight of these patients stayed in hospital for five to seven days, and five patients stayed for up to two weeks. The time from the onset of NA to the HEV diagnosis, as well as the diagnostic and therapeutic proceedings, showed a large variability. In total, 13 (81%) patients received treatment: 1/13 (8%) received intravenous immunoglobulins, 8/13 (62%) received glucocorticoids, 3/13 (23%) received ribavirin, and 6/13 (46%) received pregabalin/gabapentin. Patients with ages above the median (47 years) were more likely to be treated (p = 0.001). Conclusion: HEV-associated NA causes a relevant morbidity. In our case series neither the type of treatment nor the time of initiation of therapy had a significant effect on the duration of hospitalization or the course of the disease. The clinical presentation, the common diagnostic and therapeutic procedures, and the patients' characteristics showed large variability, demonstrating the necessity of standardized protocols for this rare but relevant disease.

Objectives:Autoimmune mechanisms are related to disease development in a subgroup of patients with psychosis. The contribution of immunoglobulin G (IgG) antibodies against myelin oligodendrocyte glycoprotein (MOG) is mainly unclear in this context. Methods:Therefore, two patients with psychosis and anti-MOG antibodies - detected in fixed cell-based and live cell-based assays - are presented. Results:Patient 1 suffered from late-onset psychosis with singular white matter lesions in magnetic resonance imaging (MRI) and intermittent electroencephalography (EEG) slowing. Patient 2 suffered from a chronic paranoid-hallucinatory disorder with intermittent confusional states, non-specific white matter alterations on MRI, a disorganised alpha rhythm on EEG, and elevated cerebrospinal fluid protein. Both patients had anti-MOG antibody titres of 1 : 320 in serum (reference < 1 : 20). Conclusions:The arguments for and against a causal role for anti-MOG antibodies are discussed. The antibodies could be relevant, but due to moderate titres, they may have caused a rather 'subtle clinical picture' consisting of psychosis instead of 'classical' MOG encephalomyelitis.

Immunological explanatory approaches are becoming increasingly important in schizophrenia research. In this context, the function of the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) plays an essential role. Different adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), are key elements in sustaining the integrity of the BBB and BCSFB. The objectives of this study were to (1) compare the levels of different cell adhesion molecules in the CSF of patients with schizophrenia spectrum disorders to those of patients with unipolar depression and (2) analyze their association with the established markers of the BBB/BCSFB function (CSF total protein and albumin quotient (AQ)). Therefore, a total of 40 patients with schizophrenia spectrum disorder and 39 age- and sex-matched control patients with unipolar depression were analyzed. The levels of soluble ICAM-1 (s-ICAM-1), soluble VCAM-1 (s-VCAM-1), and plasminogen activator inhibitor 1 (PAI-1) in the CSF were measured using a magnetic bead multiplexing immunoassay. The levels of sICAM-1 (p < 0.001), sVCAM-1 (p < 0.001), and PAI-1 (p < 0.001) in the CSF were significantly higher in patients with schizophrenia spectrum disorder than in patients with unipolar depression. In addition, a significant correlation of sVCAM-1 levels with total protein concentrations (r = 0.454, p = 0.003) and AQ levels (r = 0.512, p = 0.001) in patients with schizophrenia spectrum disorders was observed. The results revealed that sICAM-1 and sVCAM-1 levels in the CSF were higher in patients with schizophrenia spectrum disorder than in those with depression. These circulating signaling molecules may indicate endothelial dysfunction causing impaired BBB/BCSFB function in patients with schizophrenia spectrum disorders. Consistent with this view, a highly significant correlation of sVCAM-1 with CSF protein and AQs was detected. Upregulation of these cell adhesion molecules might be indicative of a proinflammatory immune response underlying the BBB/BCSFB disturbance in a subgroup of patients with schizophrenia spectrum disorders. The significance of the study is limited by its retrospective research design and by the absence of a healthy control group. The assay used was not previously established for the measurement of CSF. Further translational and controlled studies of the role of different cell adhesion molecules in schizophrenia are needed.