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Autoimmune encephalitis is increasingly recognized as a cause of psychiatric symptoms. A wide spectrum of psychiatric manifestations have been described which may precede, follow or occur independently of neurologic features. Patients typically respond to immunotherapy, however diagnosis is challenging due to phenotypic heterogeneity. The aim of this review is to provide an overview of the psychiatric features associated with encephalitis mediated by autoantibodies targeting neuronal cell-surface antigens and describe indicators of potential immunopathology underlying psychiatric manifestations., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Purpose: Despite the rapid increase in research examining outcomes in autoimmune encephalitis (AE) patients, there are few cohort studies examining cognitive outcomes in this population. The current study aimed to characterise psychometric outcomes in this population, and explore variables that may predict psychometric outcomes., Methods: This retrospective observational study collected psychometric data from 59 patients across six secondary and tertiary referral centres in metropolitan hospitals in Victoria, Australia between January 2008 and July 2019. Frequency and pattern analysis were employed to define and characterize psychometric outcomes. Univariable logistic regression was performed to examine predictors of intact and pathological psychometric outcomes., Results: Deficits in psychometric markers of executive dysfunction were the most common finding in this cohort, followed by deficits on tasks sensitive to memory. A total of 54.2% of patients were classified as having psychometric impairments across at least two cognitive domains. Twenty-nine patterns were observed, suggesting outcomes in AE are complex. None of the demographic data, clinical features or auxiliary examination variables were predictors of psychometric outcome., Conclusions: Cognitive outcomes in AE are complex. Further detailed and standardized cognitive testing, in combination with magnetic resonance imaging volumetrics and serum/cerebrospinal fluid biomarkers, is required to provide rigorous assessments of disease outcomes., (© 2022 European Academy of Neurology.)

Paralleling advances with respect to more common antibody-mediated encephalitides, such as anti-N-methyl-D-aspartate receptor (NMDAR) and anti-leucine-rich glioma-inactivated 1 (LGI1) Ab-mediated encephalitis, the discovery and characterisation of novel antibody-mediated encephalitides accelerated over the past decade, adding further depth etiologically to the spectrum of antibody-mediated encephalitis. Herein, we review the major mechanistic, clinical features and management considerations with respect to anti-γ-aminobutyric acid B (GABA B )-, anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropinoic receptor- (AMPAR), anti-GABA A -, anti-dipeptidyl-peptidase-like protein-6 (DPPX) Ab-mediated encephalitides, delineate rarer subtypes and summarise findings to date regarding seronegative autoimmune encephalitis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To evaluate the utility of electroencephalography (EEG) changes as diagnostic and prognostic biomarkers in acute autoimmune encephalitis (AIE)., Methods: One hundred and thirty-one patients with AIE were recruited retrospectively across 7 hospitals. Clinical data were collected during admission and at 12 months. EEGs were reviewed using a standard reporting proforma. Associations between EEG biomarkers, AIE subtypes, and clinical outcomes were assessed using logistic regression modeling., Results: Presence of superimposed fast activity (OR 34.33; 95% CI 3.90, 4527.27; p < 0.001), fluctuating EEG abnormality (OR 6.60; 95% CI 1.60, 37.59; p = 0.008), and hemispheric focality (OR 28.48; 95% CI 3.14, 3773.14; p < 0.001) were significantly more common in N-methyl-d-aspartate receptor (NMDAR) antibody-associated patients with AIE compared to other AIE subtypes. Abnormal background rhythm was associated with a poor mRS (modified Rankin score) at discharge (OR 0.29; 95% CI 0.10, 0.75; p = 0.01) and improvement in mRS at 12 months compared with admission mRS (3.72; 95% CI 1.14, 15.23; p = 0.04)., Significance: We have identified EEG biomarkers that differentiate NMDAR AIE from other subtypes. We have also demonstrated EEG biomarkers that are associated with poor functional outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To examine the utility of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) as biomarkers of prognosis in seropositive autoimmune encephalitis (AE)., Methods: In this multicenter study, we retrospectively analyzed 57 cases of seropositive AE with hospital admissions between January 2008 and June 2019. The initial full blood examination was used to determine each patients' NLR and MLR. The modified Rankin Scale (mRS) was utilized to assess the patients' follow-up disability at 12 months and then at final follow-up. Primary outcomes were mortality and mRS, while secondary outcomes were failure of first line treatment, ICU admission, and clinical relapse. Univariate and multivariable regression analysis was performed., Results: During initial hospital admission 44.7% of patients had unsuccessful first line treatment. After a median follow-up of 700 days, 82.7% had good functional outcome (mRS ≤2) while five patients had died. On multivariable analysis, high NLR was associated with higher odds of first line treatment failure (OR 1.32, 95% CI 1.03-1.69, p = 0.029). Increased MLR was not associated with any short or long-term outcome., Conclusions: NLR on initial hospital admission blood tests may be provide important prognostic information for cases of seropositive AE. This study demonstrates the potential use of NLR as a prognostic marker in the clinical evaluation of patients with seropositive AE., Competing Interests: WD’S’s salary is part-funded by The University of Melbourne. He has received travel, investigator-initiated, scientific advisory board and speaker honoraria from UCB Pharma Australia & Global; investigator-initiated, scientific advisory board, travel and speaker honoraria from Eisai Australia & Global; advisory board honoraria from Liva Nova; educational grants from Novartis Pharmaceuticals, Pfizer Pharmaceuticals and Sanofi-Synthelabo; educational, travel and fellowship grants from GSK Neurology Australia, and honoraria from SciGen Pharmaceuticals. AB is on the editorial boards for Neurology and International Stroke Journal, and an Australian Scientific Advisory Board for Biogen. TK served on scientific advisory boards for Roche, Celgene, Sanofi-Genzyme, Novartis, Merck, and Biogen, steering committee for Brain Atrophy Initiative by Sanofi-Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi-Genzyme, Teva, BioCSL, and Merck and received research support from Biogen. HB’s institution receives funding from Biogen, Roche, Merck, and Novartis for speaker engagements, study steering and advisory committee service. He is on the editorial board of Multiple Sclerosis and Related Disorders and the Steering committee of the Brain Health Initiative (Oxford Health Policy Forum). TO’B receives research funding from Biogen, UCB Pharma, Eisai Pharma, Anavex Pharmaceuticals, Zynerba Pharmaceuticals, and serves on the scientific advisory boards for UCB Pharma, Eisai Pharmaceuticals, Zynerba Pharmaceuticals, ES Therapeutics, Seqirus Pharmaceuticals. MM’s institution receives funding from Merck. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Broadley, Wesselingh, Seneviratne, Kyndt, Beech, Buzzard, Nesbitt, D’Souza, Brodtmann, Kalincik, Butzkueven, O’Brien, Monif and Australian Autoimmune Encephalitis Consortium.)

Anti-Leucine Glioma Inactivated 1 (LGI-1) autoimmune encephalitis (AE) is a rare neuroinflammatory brain condition. Individuals afflicted with this condition can present with cognitive and psychological manifestations that can impact the individual's quality of life, day to day functioning, independence, return to work and interpersonal relationships. Our knowledge of the cognitive profiles and disease associated psychopathology is severely lacking. This review provides a comprehensive summary of the currently available literature, conceptualising our current understanding of the neuropsychological manifestations of anti LGI-1 AE and summarises methodological limitations of the current research to inform and improve future investigations. Key Terms: Autoimmune Diseases; Neuroimmunology; Autoimmune Encephalitis, Limbic Encephalitis; Anti-LGI1 Encephalitis, LGI1; Neuropsychology, Cognitive Assessment., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Epilepsy is a common neurological disorder that increases the risk of morbidity and mortality. Autoimmune epilepsy is a subset of epilepsy that occurs in the setting of autoimmunity, such as in autoimmune encephalitis (AIE). AIE is an autoimmune disorder characterized by immune-mediated neuroinflammation resulting in a variety of neurological symptoms, including psychiatric disturbance, cognitive dysfunction, and seizures. Seizures in AIE are thought to be a result of antibodies directed against neuronal cell-surface proteins involved in synaptic transmission. The role of blood-brain barrier dysfunction, myeloid cell infiltration, and the initiation of proinflammatory cascades in epileptogenesis has been shown to be important in animal models and human patients with epilepsy. Epileptogenesis in AIE is likely to arise from the synergistic effect of both innately driven neuroinflammation and antibody-induced hyperexcitability. Together, these processes produce persistent drug-resistant seizures that contribute to the morbidity seen in AIE. Understanding the proinflammatory pathways involved in this process may improve diagnostics and provide alternative treatment targets in AIE., (© 2020 International League Against Epilepsy.)

The autoimmune encephalitides are a group of autoimmune conditions targeting the central nervous system and causing severe clinical symptoms including drug-resistant seizures, cognitive dysfunction and psychiatric disturbance. Although these disorders appear to be antibody mediated, the role of innate immune responses needs further clarification. Infiltrating monocytes and microglial proliferation at the site of pathology could contribute to the pathogenesis of the disease with resultant blood brain barrier dysfunction, and subsequent activation of adaptive immune response. Both innate and adaptive immune cells can produce pro-inflammatory molecules which can perpetuate ongoing neuroinflammation and drive ongoing seizure activity. Ultimately neurodegenerative changes can ensue with resultant long-term neurological sequelae that can impact on ongoing patient morbidity and quality of life, providing a potential target for future translational research.

Objective: To perform a systematic review of the current scientific literature in order to identify variables associated with patient prognosis in autoimmune encephalitis., Methods: We performed a systematic literature search using MEDLINE, Embase, PubMed and PsychInfo databases. We selected studies that explored the correlation between early clinical and paraclinical findings, and patient outcomes. Data was extracted, analyzed and recorded in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines., Results: Forty four publications detailing 2823 subjects matched our inclusion criteria. There was considerable heterogeneity in methodology, patient profile, investigation results and clinical outcome measures. Findings were often discrepant for cases of anti-NMDAR encephalitis when compared with other causes of autoimmune encephalitis. Delay in immunotherapy contributed to a variety of worse outcomes for patients with different subsets of autoimmune encephalitis. Altered consciousness, ICU admission and no use of immunotherapy were variables associated with poor prognosis in anti-NMDAR encephalitis. Older age, sex, the presence of status epilepticus, CSF abnormalities and MRI changes were unlikely to have significant prognostic value. The influence of antibody titers, autonomic dysfunction and underlying malignancy was unclear., Conclusions: A number of variables were identified to have potential predictive value for outcomes in autoimmune encephalitis. Heterogeneous study design, size and quality were major limiting factors in this review., (Copyright © 2018 Elsevier Ltd. All rights reserved.)