Morphometric MRI findings in patients with suspected autoimmune psychosis spectrum syndromes and association with EEG slowing, CSF changes, and psychometric/neuropsychological findings

IntroductionPatients 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 methodsIn 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.ResultsPatients 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.DiscussionAutoantibody-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

Brain Structural Correlates of EEG Network Hyperexcitability, Symptom Severity, Attention, and Memory in Borderline Personality Disorder

Introduction: Previous neuroimaging studies have reported structural brain alterations and local network hyperexcitability in terms of increased slow-wave electroencephalography (EEG) activity in patients with borderline personality disorder (BPD). In particular, intermittent rhythmic delta and theta activity (IRDA/IRTA) has drawn attention in mental health contexts due to its links with metabolic imbalances, neuronal stress, and emotional dysregulation—processes that are highly pertinent to BPD. These functional disturbances may be reflected in corresponding structural brain changes. The current study investigated cortical thickness and subcortical volumes in BPD and examined their associations with IRDA/IRTA events per minute, symptom severity, and neuropsychological measures. Methods: Seventy female BPD patients and 36 age-matched female healthy controls (HC) were included (for clinical EEG comparisons even 72 patients were available). IRDA/IRTA rates were assessed using an automatic independent component analyses (ICA) approach. T1-weighted MRI data were obtained using a MAGNETOM Prisma 3T system and analyzed with FreeSurfer (version 7.2) for subcortical structures and CAT12 for cortical thickness and global volume measurements. Psychometric assessments included questionnaires such as Borderline Symptom List (BSL-23) and Inventory of Personality Organization (IPO). Neuropsychological performance was evaluated with the Test for Attentional Performance (TAP), Culture Fair Intelligence Test (CFT-20-R), and Verbal Learning and Memory Test (VLMT). Results: Between-group comparisons exhibited no significant increase in IRDA/IRTA rates or structural abnormalities between the BPD and HC group. However, within the BPD group, cortical thickness of the right isthmus of the cingulate gyrus negatively correlated with the IRDA/IRTA difference (after minus before hyperventilation, HV; p < 0.001). Furthermore, BPD symptom severity (BSL-23) and IPO scores positively correlated with the thickness of the right rostral anterior cingulate cortex (p < 0.001), and IPO scores were associated with the thickness of the right temporal pole (p < 0.001). Intrinsic alertness (TAP) significantly correlated with relative cerebellar volume (p = 0.01). Discussion: While no group-level structural abnormalities were observed, correlations between EEG slowing, BPD symptom severity, and alertness with cortical thickness and/or subcortical volumes suggest a potential role of the anterior cingulate cortex, temporal pole, and cerebellum in emotion regulation and cognitive functioning in BPD. Future research employing multimodal EEG-MRI approaches may provide deeper insights into the neural mechanisms underlying BPD and guide personalized therapeutic strategies

Anti-MOG autoantibody-associated schizophreniform psychosis

AbstractObjectives: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 &lt; 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.</jats:sec

Spectrum of novel anti–central nervous system autoantibodies in the cerebrospinal fluid of 119 patients with schizophreniform and affective disorders

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.</p

Spectrum of Novel Anti-Central Nervous System Autoantibodies in the Cerebrospinal Fluid of 119 Patients With Schizopheniform and Affective Disorders

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. Conclusion: The study demonstrates five novel autoantibody-binding patterns on brain tissue of patiens with schizophreniform and affective syndromes. CSF yielded positive findings more frequently than scrum analysis. The frequency and spectrum of autoantibodies in these patient groups may be broader than previously thought