BACKGROUND:Glucocorticoids (GCs) are standard treatment for giant cell arteritis (GCA). Many patients experience relapses or GC-related toxicity. Secukinumab, a fully human monoclonal antibody that selectively inhibits interleukin-17A, is being studied as additional therapy for GCA. METHODS:GCAptAIN was a randomized, parallel-group, double-blind, placebo-controlled, multicenter phase 3 trial. Patients with new-onset or relapsing GCA were initially randomly assigned (2:1) to either 300 mg of secukinumab (SEC-300) or placebo for 52 weeks. After a protocol amendment, patients were randomly assigned (1:1:1) to either SEC-300, 150 mg of secukinumab (SEC-150), or placebo. Patients in the SEC-300 and SEC-150 groups received a 26-week GC taper. Patients in the placebo group received a 52-week GC taper. The primary outcome was the proportion of patients experiencing sustained remission in the SEC-300 versus placebo groups at week 52. Sustained remission in patients in the SEC-150 group versus patients in the placebo group enrolled after the protocol amendment was a secondary outcome. Adverse events (AEs) and serious AEs (SAEs) were assessed. RESULTS:A total of 140 patients in the SEC-300 group, 98 in the SEC-150 group, and 115 in the placebo group (19 patients were enrolled in the placebo group before and 96 after the protocol amendment) were analyzed for efficacy and safety. The proportion of patients achieving sustained remission at week 52 was 25.6% for SEC-300 versus 16.9% for placebo (marginal difference: 8.7 percentage points; 95% confidence interval [CI], -1.3 to 18.8; P=0.09) and 19.4% for SEC-150 versus 17.7% for placebo (marginal difference, 1.6 percentage points; 95% CI, -9.2 to 12.4). AEs occurred in 92.9%, 95.9%, and 97.4% of patients in the SEC-300, SEC-150, and placebo groups, respectively. SAEs occurred in 20.0%, 27.6%, and 32.2% of patients in the SEC-300, SEC-150, and placebo groups, respectively. Serious infections occurred in 5.0%, 9.2%, and 6.1% of patients in the SEC-300, SEC-150, and placebo groups, respectively. CONCLUSIONS:Sustained remission at week 52 did not differ significantly between patients with GCA randomly assigned to receive SEC-300 with a 26-week GC taper versus placebo with a 52-week GC taper. (Funded by Novartis Pharma; EudraCT number, 2020-004809-31; ClinicalTrials.gov number, NCT04930094.).

OBJECTIVES:Avacopan, an oral C5a receptor antagonist, is approved for treatment of severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in combination with rituximab or cyclophosphamide. This study evaluated its real-world efficacy, safety and glucocorticoid-sparing effects. METHODS:This retrospective single-centre study included 35 patients with new-onset or relapsing AAV treated with avacopan plus standard induction therapy (rituximab, cyclophosphamide or both). Outcomes were compared with 70 matched controls receiving standard therapy. Primary endpoints were remission (Birmingham Vasculitis Activity Score (BVAS)=0, prednisolone ≤5 mg/day) at 6 and 12 months. Secondary endpoints included relapse, renal function, glucocorticoid exposure and adverse events. RESULTS:Baseline characteristics were generally comparable, although median estimated glomerular filtration rate (eGFR) was lower in the avacopan group (24 vs 49 mL/min). Induction therapy included rituximab (28%), cyclophosphamide (11%) or combination therapy (61%), reflecting severe disease. Remission rates were similar at 6 months (69% vs 68%) but tended to be higher with avacopan at 12 months (86% vs 68%; p=0.11). Relapses occurred less frequently with avacopan (16% vs 51%, p=0.003), including after treatment discontinuation. Avacopan was associated with accelerated glucocorticoid tapering (≤5 mg/day; 102 vs 164 days, p<0.001), lower cumulative doses (3266 vs 4288 mg, p=0.008) and greater renal function improvement (ΔeGFR+18 vs +7 mL/min after 1 year). Nine patients (26%) discontinued avacopan due to adverse events. CONCLUSION:In a real-world practice, avacopan was effective with an acceptable safety profile, enabling steroid sparing, improved renal recovery and reduced relapse rates, including in patients receiving combined induction therapy. Benefits persisted beyond 12 months, but prospective confirmation of these presumed long-term benefits is needed.

Background: For giant cell arteritis (GCA), a north-south gradient in incidence and prevalence has been described, peaking in Scandinavia. Objective: This analysis aimed to obtain up-to-date, representative data on the prevalence and incidence of GCA in Germany, updating the old, regional information on low incidence and prevalence rates. Design: Cross-sectional analysis using a large German health insurance database. Methods: This study is based on a cross-sectional analysis of claims data from the InGef (Institute for Health Research Berlin GmbH) research database, which includes a representative sample of 4.8 million insured individuals. Individuals aged ⩾50 years with continuous insurance coverage for a 3-year baseline period and the subsequent 2 years for longitudinal analysis were included. Estimates were standardised and projected to the German population. Results: Each year from 2018 to 2021, 1.7 million insured individuals met the inclusion and exclusion criteria. Extrapolated to the German population ⩾50 years in 2021, the incidence was 24/100,000, and the prevalence was 146/100,000. Diagnosis was made predominantly in outpatient settings by general practitioners (GP, 31.9%) and internists (19.5%), followed by rheumatologists (13.1%) and ophthalmologists (5.7%). Within 2 years, 16.3% of incident patients were referred to rheumatologists for treatment after diagnosis. Treatment was most commonly initiated by GPs (45.8%), followed by rheumatologists (36.1%), and included glucocorticoids (88.2%), methotrexate (26.7%), and tocilizumab (14.1%). Most common comorbidities of prevalent patients comprised arterial hypertension (77.2%), dyslipidaemia (55.0%), diabetes mellitus (28.8%), osteoporosis (34.6%), and cataract (31.2%). Conclusion: Contrary to previous reports, Germany has higher incidence and prevalence rates of GCA than previously assumed. Only approximately one-third of the incident patients were initially treated by rheumatologists. Comorbidities such as diabetes or cardiovascular diseases were common.

OBJECTIVE:Eosinophilic granulomatosis with polyangiitis (EGPA) is a small vessel vasculitis characterized by eosinophilia, asthma, and ear, nose, and throat (ENT) involvement. Although glucocorticoids (GCs) are effective in controlling symptoms, relapses and GC dependence are common. The aim of this study was to develop predictive models for vasculitis relapse and GC-dependent asthma and/or ENT symptoms. METHODS:This multicenter European retrospective cohort study included patients with EGPA fulfilling the 2022 American College of Rheumatology/EULAR criteria. Using Fine-Gray and logistic regression, we developed two multivariable prediction models, one for vasculitis relapse and another for GC-dependent asthma and/or ENT symptoms at 2 Internal validation was performed using bootstrapping. RESULTS:A total of 809 patients were observed for a median of 72 months (interquartile range 37-115). Vasculitis relapse occurred in 228 patients with a 12-year cumulative incidence of 41.2% (95% confidence interval 36.3-46.8). GC-dependent asthma and/or ENT symptoms were observed in 66.4% at two years. Predictors of vasculitis relapse included age (nonlinear), GC-dependent asthma before EGPA diagnosis (hazard ratio [HR] 1.57), arthralgia (HR 1.27), myocarditis (HR 1.74), peripheral neuropathy (HR 1.39), myeloperoxidase-antineutrophil cytoplasmic antibody (HR 1.56), and baseline eosinophil count (nonlinear). Predictors of GC-dependent asthma and/or ENT symptoms included older age (odds ratio [OR] 0.98 per year), GC-dependent asthma at diagnosis (OR 1.50), chronic sinusitis (OR 1.78), and baseline eosinophil count (OR 0.70 per 109/L). CONCLUSION:Using a large cohort with EGPA, we developed predictive models for vasculitis relapse and GC-dependent asthma and/or ENT symptoms. These tools may help guide treatment decisions. Prospective external validation in the current therapeutic era is warranted.

Objective Axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) are overlapping yet distinct conditions within the SpA spectrum. As divergent immunophenotypes may influence disease course and therapeutic response, we compared immune cell subsets, cytokine profiles, and inflammatory mediators. Methods Peripheral blood mononuclear cells (PBMCs) from 179 patients (88 axSpA, 91 PsA) and 49 healthy donors were profiled using spectral flow cytometry, comprising 230 million acquired events and 55 million quality‐controlled cells. Immune subsets, activation‐ and differentiation‐associated markers, and cytokines were analyzed to define disease‐specific profiles. Results axSpA and PsA exhibited distinct immunophenotypic profiles. axSpA was characterized by expansion of double‐negative and γδ T cells, increased plasmablasts and CD21 low B cells, and higher expression of activation‐associated markers (CD80, CD86, CD95), consistent with dysregulated innate‐like immune activation. PsA showed increased dendritic cells and a higher frequency of IgM + IgD − memory B cells. Both diseases exhibited Th1 enrichment; however, axSpA showed additional Th17 skewing and increased expression of activation‐ and checkpoint‐associated markers (HLA‐DR, CD38, PD‐1), whereas PsA displayed more central memory CD4 + T cells and lower PD‐1 expression. Cytokine profiling revealed elevated inflammasome‐related and innate cytokines in axSpA, whereas PsA showed increased soluble interleukin‐2 (IL‐2) receptor, IL‐17A, soluble tumor necrosis factor receptor type I, and vascular‐associated inflammatory mediators. Regularized regression identified a stable immune signature distinguishing axSpA from PsA (cross‐validated area under the receiver operating characteristic curve 0.94). Conclusion axSpA and PsA share overlapping yet distinguishable immunophenotypic signatures. axSpA shows enrichment of innate‐associated and broadly activated immune features, whereas PsA is characterized by adaptive and memory‐associated immune responses. These findings may support biomarker‐guided stratification within the SpA spectrum. image

Introduction Obsessive-compulsive disorder (OCD) is associated with a dysfunction of the cortico-striato-thalamo-cortical loops and overarching functional networks as well as with disturbances in serotonin, dopamine, and glutamate neurotransmission. In rare individual cases, the underlying cause is an autoimmune OCD. Innovative multimodal diagnostic work-ups can support the identification of mild neuroinflammation in clinical practice as shown in the present paradigmatic case. Case study Susceptibility-weighted magnetic resonance imaging (MRI) of a 28-year-old female patient with severe OCD revealed a left thalamic microbleed. Subsequent diffusion tensor imaging tractography showed that the thalamus microbleed involved centro-thalamic and some fronto-thalamic fibers. A comparison of the patient's diffusion microstructure imaging (DMI) results with those of a matched healthy control group revealed widespread alterations in cerebral microstructure. Elevated free fluid in left temporal regions and relative cortical cellular loss were observed, compatible with an inflammatory process in terms of edematous changes. The frontal regions displayed an increase in the extracellular compartment accompanied by a decrease of the dendritic structures. [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) showed a slightly lower cortical FDG metabolism of the right hemisphere, most likely within the physiologic range. Electroencephalography identified electrophysiological abnormalities with intermittent rhythmic slowing, and a tissue-based assay on unfixed mouse brain slices found finely dotted binding of cerebrospinal fluid immunoglobulin G autoantibodies against nuclear antigens (ANAs). With guideline-compliant treatment and vitamin D supplementation, great clinical improvement and markedly reduced microstructural DMI alterations in MRI were achieved in the follow-up after about half a year. Discussion This case study illustrates how advanced multimodal diagnostics can contribute to a better pathophysiological understanding of OCD with a frontal disconnection and further mild neuroinflammatory changes. An underlying autoimmune cause was supported by the detection of intrathecal autoantibodies against nuclear antigens. ANA-associated diseases, such as neuropsychiatric lupus, have previously been associated with microbleeds. Deep clinical phenotyping approaches could assist in establishing precision medicine approaches for OCD.

BACKGROUND:Granulomatosis with polyangiitis (GPA) and eosinophilic granulomatosis with polyangiitis (EGPA) are distinct forms of antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). Increasing evidence suggests overlapping features, particularly in proteinase 3 (PR3)-ANCA-positive EGPA and GPA with eosinophilia. This study aimed to characterize overlapping EGPA/GPA forms and assess their clinical and therapeutic implications. METHODS:We conducted a European, multicenter, observational study, including 135 patients with overlapping EGPA/GPA features. Definitions were based on ACR/EULAR classification criteria and other clinical and biological findings. Clinical, biological, and histological characteristics were analyzed using unsupervised hierarchical clustering approach. Comparisons were made with established EGPA and GPA control cohorts. RESULTS:Three clusters emerged: Cluster 1, a hybrid phenotype (pulmonary nodules, PR3-ANCA positivity, high relapse rate); Cluster 2, a systemic inflammatory phenotype (constitutional symptoms, PR3-ANCA positivity, moderate renal involvement); and Cluster 3, a severe vasculitis form (severe renal disease, alveolar hemorrhage). Including typical EGPA and GPA control cohorts revealed two main clusters a posteriori: an EGPA cluster and a GPA cluster. Cluster 1 overlapped with both EGPA and GPA clusters, whereas Clusters 2 and 3 predominantly aligned with GPA. Kaplan-Meier analysis revealed that Cluster 1 and the typical EGPA cohort had the best overall survival, whereas Cluster 3 had the poorest survival. Relapse-free survival was highest in typical EGPA and poorest in Cluster 3 and typical GPA. CONCLUSION:This study delineates the heterogeneity of EGPA/GPA overlap and underscores the need for personalized treatment approaches. Future prospective studies should explore targeted therapies, including rituximab and IL-5 blockade, in these overlapping AAV subtypes.

INTRODUCTION:Complex mixed presentations of severe mental disorders (SMD) with treatment resistance pose major challenges in clinical practice. The role of novel neuronal antibodies in cerebrospinal fluid (CSF) is largely unexamined in this context. METHODS:A well-studied paradigmatic case of a 36-year-old female patient is reported. RESULTS:She presented with attention-deficit/hyperactivity disorder-like symptoms (including frequent sensory overload), severe pain (pre-diagnosed as fibromyalgia and somatoform pain disorder), and motor tics. In addition, she developed secondary depressive symptoms. Various psychopharmacological treatment attempts were unsuccessful or not tolerated. The diagnostic routine work-up with a wide range of blood tests, electroencephalography (EEG), routine magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analyses, and [18F]fluorodeoxyglucose positron emission tomography revealed no clear pathological findings. Tissue-based assays using CSF material found strong immunoglobulin G antibody staining specifically directed against a cell population in the thalamus. Neurotransmitter measurements detected low GABA, glutamate and serotonin concentrations as well as high dopamine levels in the CSF. Different MRI-based analyses indicated no neurostructural alterations in the thalamus; however, left mesiotemporal volume loss was identified. The independent component analysis of the EEG showed left temporal theta waves, partly resembling spike-wave-complexes. Immunotherapy using high-dose steroids resulted in a partial improvement with subjectively reduced stimulus overload, intermediate disappearance of pain, and fewer tics. The improvement could not be objectified psychometrically/neuropsychologically. The mesiotemporal volume loss was no longer present. There were no relevant changes in further research MRI measurements of the thalamus including arterial spin labeling, diffusion tensor imaging, and diffusion microstructure imaging from pre to post-immunotherapy. DISCUSSION:Novel antibodies against strategic brain structures, such as the thalamus, might be associated with some complex SMD. Further immunopsychiatric research in this direction holds promise for a better understanding of similar patients.

A 48-year-old patient underwent lung transplantation because of severe COVID-19, which aggravated his underlying interstitial lung disease, despite the presence of detectable SARS-CoV-2. Subsequently, the graft is re-infected early in the post-procedural phase, leading to viral persistence for more than five months. By analyzing viral evolution and effector immune response within the transplanted organ, we observe three main findings. First, virus evolution differs in the transplanted organ compared to that in the upper respiratory tract and is affected by monoclonal SARS-CoV-2-specific antibodies and molnupiravir. Second, we show the potential clinical relevance of T cell HLA restriction that may facilitate viral clearance in the upper respiratory tract compared to the ongoing viral replication in the HLA mismatch organ. Third, close monitoring and modulation of immunosuppressive and antiviral therapy enables viral clearance in a lung transplantation setting despite incomplete SARS-CoV-2 clearance prior to transplantation.

BACKGROUND:Giant cell arteritis (GCA) of the vertebral artery (VA) is a rare but serious cause of ischemic stroke, however, the long-term clinical and sonographic course of GCA patients with VA involvement (VA+) is poorly understood. METHODS:All patients with suspected GCA who were consecutively referred to our ultrasound (US) lab over a 12-year-period were analyzed. US examination (GCA-specific) of the cranial and cervical arteries was performed. Patients with a positive US diagnosis of GCA were identified, and further analysis was restricted to VA+ patients. Follow-up data were extracted from our hospital database. RESULTS:Among the 785 patients screened for GCA, 220 showed typical US-based findings for GCA, 74 (34 %) of whom were VA+. Fourteen VA+ patients (19 %) had vertebrobasilar ischemia at presentation (11 stroke, 3 TIA). Cerebral ischemia was more frequent in patients with severe compared to moderate VA occlusive disease (35 % vs 9 %; p = 0.0099, OR = 5.39, 95 % CI 1.50-9.42). Two patients died from severe initial stroke. Follow-up data were available for 34 VA+ patients (46 % of all VA+ patients; median period, 740 days), where 13 (38 %) displayed stable US alterations to the VA, 14 (41 %) a regression and 7 (21 %) a progression of stenosis. Four patients (12 %) had vertebrobasilar re-stroke, 3 of them within 30days of treatment initiation. CONCLUSION:One-third-of patients with cranial GCA were VA+, 19 % of whom had vertebrobasilar stroke, of which most had severe VA occlusive disease. Significant rates of stenosis progression and recurrent stroke therefore call for early intensive immunosuppressive treatment.

OBJECTIVES:Epidemiological data on polymyalgia rheumatica (PMR) in Germany is limited. Current national prevalence estimates are low by international standards. This study aimed to gain up-to-date data representative of Germany. METHODS:A cross-sectional analysis was conducted on a sample of 4.8 million insured individuals, representative of the German population, from the InGef (Institute for Health Research Berlin GmbH) research database. Inclusion criteria were age ≥50 years, continuous insurance status for a base period of 3 years and for the subsequent 2 years for longitudinal analysis. Results were additionally extrapolated to the German population. RESULTS:Each year from 2018 to 2021, around 1.7 million insured individuals were included in the study. Extrapolated to the German population in 2021, the incidence was 111/100 000 and the prevalence was 937/100 000. Diagnosis was made predominantly in outpatient settings (86.7%) most frequently by general practitioners (GP; 37.1%), internists (22.2%), rheumatologists (11.4%) and orthopaedists (10.2%). An additional 21% were referred to rheumatologists for treatment after diagnosis. Treatment was most commonly initiated by GPs, followed by rheumatologists, and included methotrexate in 19.8%. Most common comorbidities of prevalent patients comprised arterial hypertension (75.9%), dyslipidaemia (55.0%), diabetes mellitus (29.7%), osteoporosis (27.1%), coronary heart disease (23.4%) and cataract (24.3%). CONCLUSION:This analysis revealed that PMR occurs more frequently in individuals aged 50 or older in Germany than previously assumed. Diagnosis is primarily made in general practice settings, with about one-third of patients being treated by rheumatologists. Comorbidities such as diabetes mellitus or cardiovascular diseases are common in the prevalent population.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a prototypic autoimmune disease, with a subset of AAV patients manifesting anti-myeloperoxidase (MPO) IgG. Patients with AAV respond positively to B cell-targeting and complement-targeting therapies, but disease flares are not uncommon. Here, by comparing samples from healthy individuals and MPO+ AVV patients, we show that B cell autoreactivity against MPO in the circulation of patients is dominated by CD27+IgM+ B cells whereas MPO-specific IgG+ cells are infrequent. Additionally, while naive anti-MPO-IgM B cells are present in both patients and controls and produce anti-MPO IgM upon stimulation, anti-MPO-IgM memory B cells and serum anti-MPO IgM are features of patients. Our results thus hint that defective elimination of B cell reactivity to MPO in the human repertoire, the presence of activated IgM+ anti-MPO B cells in disease, and a dominant role for anti-MPO IgM in complement activation, may all contribute to MPO+ AAV etiology and thereby serve as potential target for therapy.

IntroductionAnti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a neuropsychiatric disorder with additional psychiatric features caused by NMDA-R immunoglobulin G (IgG) antibodies in cerebrospinal fluid (CSF). This report presents the follow-up of a patient in whom we assumed mild NMDA-R encephalitis in the first psychotic episode.Case studyA patient with a prior episode of an acute polymorphic psychotic syndrome relapsed five and a half years later following a severe COVID-19 infection. Serum NMDA-R antibodies were again detected with a titer of max. 1:320 using fixed-cell-based assays, but conventional magnetic resonance imaging (MRI), electroencephalography (EEG), and CSF findings were largely normal. NMDA-R antibody levels in serum decreased to 1:80 after approximately one month without immunotherapy. [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) still revealed pronounced metabolism of the association cortices (clearly more pronounced in the first episode with an encephalitis-like pattern at that time). Advanced MRI analyses including diffusion microstructure imaging (DMI) showed frontal and thalamic microstructural alterations compatible with edematization (but also far less accentuated than in the first episode). Further advanced antibody tests of CSF (approx. 1 month after symptom onset) using a live-cell-based and different tissue-based assays were negative for NMDA-R IgG antibodies. Research mass spectrometry of the CSF identified neurotransmitter-precursor shortages, increased turnover of tryptophan into quinolinic acid, and low-glucose/lactate levels. Immunotherapy (performed after the initial assumption of an autoimmune cause) with steroids led to clinical improvement of residual symptoms. After approximately three months, NMDA-R IgG serum antibodies were no longer detectable; however, FDG-PET/DMI follow-up revealed no relevant changes.DiscussionThe international consensus criteria for a probable/definite diagnosis of NMDA-R encephalitis or autoimmune psychosis were not fulfilled, especially as no NMDA-R IgG antibodies were identified in CSF using different antibody assays and EEG/CSF routine findings were inconspicuous. NMDA-R encephalitis was therefore not diagnosed (as initially suspected). Independent of the NMDA-R IgG antibodies, there were possible signs of an autoimmune process. For a better understanding of similar patients, multimodal diagnostic approaches including complementary antibody tests could be promising.

Introduction: Autoimmune social anxiety disorders have not yet been described in the literature. Methods: Therefore, this case of a patient with possible autoimmune-mediated social anxiety disorder is presented. Due to treatment resistance and high serum streptococcal antibody levels, a comprehensive diagnostic work-up was performed. Results: The 19-year-old female patient presented with predominant social anxiety disorder and secondary depression. Testing for all known characterized neuronal and glial IgG antibodies identified slightly positive (“+”) recoverin IgG antibodies only in the serum (using an immunoassay). Cerebrospinal fluid (CSF) analysis using a tissue-based assay on unfixed mouse brain slices revealed moderate immunoglobulin G (IgG) anti-nuclear binding and a specific strong IgG binding against cell nuclei of the Bergmann glia in the cerebellum. No clear pathology was noted in conventional magnetic resonance imaging (MRI), voxel-based morphometry, and cerebral blood flow. Diffusion microstructure imaging (DMI) revealed a substantial reduction of the intraneurite volume fraction in the cerebellar gray and white matter. This was accompanied by a compensatory increase in free fluid and the extra-neurite volume fraction. Alterations in the striatum were also observed with DMI. Electroencephalography (EEG) showed intermittent generalized slowing with underlying left frontal, right temporal, and left temporo-occipital components (detected via independent component analysis of the EEG). The [18F]fluorodeoxyglucose positron emission tomography of the whole body detected a slight polyserositis and no malignant tumor. Discussion: This is the first description of a case with evidence of a possible antibody-mediated cerebellar dysfunction associated with social anxiety disorder. The testing for all characterized neuronal/glial antibodies showed only weakly positive recoverin antibodies in the serum, which, however, were not detectable in the CSF. Therefore, novel CSF antibodies directed against cell nuclei of the Bergmann glia in the cerebellum could be assumed. DMI alterations in the cerebellum were in principle compatible with neuroinflammation with edematization and cellular activation. In addition, the further DMI alterations in the striatum and the fronto-temporal generators of EEG slowing suggest an involvement of the “anxiety network”. Further immunopsychiatric research in anxiety disorders might contribute to identifying an autoimmune subtype and potentially immunomodulatory treatment options.

Introduction:Patients with autoimmune encephalitis - who often have accompanying psychiatric symptoms - frequently have electroencephalography (EEG) changes and normal conventional magnetic resonance imaging (MRI) findings. The aim of this paper was to analyze automated EEG and morphometric MRI findings in psychiatric patients with suspected autoimmune psychosis (AP) spectrum syndromes versus controls and the correlation of MRI measures with EEG, cerebrospinal fluid (CSF), and psychometric/neuropsychological findings. Participants and methods:In total, forty patients were included. Suspected AP spectrum syndromes were defined broadly based on the autoimmune psychiatric syndrome concept. All patients showed signs of an autoimmune process. That is, upon further diagnostic testing, they tested at least positive for well-characterized neuronal antibodies, novel central nervous system antibodies, or well-characterized systemic antibodies with brain involvement. For EEG, thirty-seven matched patient-control pairs, and for structural MRI, thirty-five patients and matched controls, were available. EEG analysis for intermittent rhythmic delta/theta activity (IRDA/IRTA) was performed using independent component analysis. MRI scans were analyzed using FreeSurfer (7.2) for the subcortical measures and CAT12 for cortical thickness and global volumes. Results:Patients did not show significantly increased IRDA/IRTA rates. Regarding brain volumes, there was a significant decrease in grey matter volume/total intracranial volume (TIV) (p=0.027) and a significant increase in CSF/TIV (p=0.027), which remained significant after correction for multiple comparisons. Further differences with lower white matter volume/TIV, reduced cortical thickness in the left parahippocampal and transversotemporal gyri and an increase in the volume of the left lateral ventricle of patients did not remain significant after correcting for multiple testing. White blood cell counts in the CSF of the whole patient group correlated positively with increased hippocampal volumes. Brain volumes did not correlate with psychometric scales, but with several neuropsychological scores. Discussion:Autoantibody-associated suspected AP spectrum syndromes seem to be associated with slight global grey matter volume reductions and secondary increased CSF volumes. Associations between hippocampal volume increases and inflammatory CSF markers could, in contrast, reflect edematous swelling within the limbic system. Further multimodal imaging studies of more homogeneous AP groups might be promising to detect morphometric correlates.

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic necrotising vasculitis characterised by tissue and blood hypereosinophilia. Cardiac involvement has previously been identified as the most significant predictor of mortality.Objective To identify and characterise previously untreated patients with EGPA and their cardiac manifestations at disease onset.Methods A retrospective monocentre study was conducted on 103 patients. Upon patient presentation, detailed multidisciplinary physical evaluations and laboratory diagnostics were performed. Cardiac events were defined as EGPA-related abnormalities in ECG, echocardiography, cardiac MRI, invasive coronary angiography or cardiac histopathology.Results Cardiac manifestations were diagnosed in 36 of 103 patients with EGPA (35%). Patients with EGPA with cardiac involvement (EGPA-CI) exhibited typical symptoms of EGPA concomitant with elevated cardiac biomarkers. Pericarditis (77%), cardiomyopathy with cardiac failure (55%) and definite myocarditis (36%) were the most common diagnoses, which in some cases resulted in cardiogenic shock (14%) or cardiac arrest (6%). Vasospastic coronary arteries causing myocardial infarctions were identified as a life-threatening cardiac manifestation in 8% of patients with EGPA-CI. Overall, patients with EGPA-CI presented with significantly higher disease activity and worse prognosis, with elevated median eosinophilic count and C-reactive protein levels.Conclusions Cardiac involvement is a common initial manifestation of EGPA and is associated with elevated systemic disease activity. In addition to pericarditis and myocarditis, coronary vasospasms were identified as a rare and severe manifestation of EGPA that may mimic myocardial infarction. Consequently, at the early stage of disease, patients may present with advanced cardiac impairment, emphasising the necessity of prompt diagnostic and therapeutic intervention to positively affect prognosis.