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Background: Autoimmune encephalitis (AE) is an increasingly recognized neuroinflammatory disease entity in which early detection and treatment leads to the best clinical outcomes. Movement disorders occur in AE but their characteristics are not well defined. Objectives: To identify the frequency, classification, and prognostic significance of movement disorders in AE. Methods: We conducted a systematic review and random-effects meta-analysis of movement disorders in cell surface antibody mediated AE. The frequency of any movement disorder as well as the classification of movement disorders in AE serotypes was determined. We looked at adults 18 years and older and included publications that described at least 10 cases. We used the following four electronic databases: Medline (Ovid), EMBASE (Ovid), APA Psychinfo, and Cochrane library. Results: A total of 1,192 titles and abstracts were reviewed. Thirty-seven studies were included in the final meta-analysis. At least one kind of movement disorder was present in 40% of the entire AE cohort, 53% with anti-NMDA receptor antibodies, 33% with anti-CASPR2 antibodies, 30% with anti-LGI1 antibodies and 13% with anti-GABA receptor antibodies. Dyskinesia was the commonest movement disorder in anti-NMDA antibody mediated AE and faciobrachial dystonic seizures were most frequent in anti-LGI1 antibody mediated AE. Patients with amovement disorder tended to have a highermortality. The risk of bias in the included studies was mostly moderate or high. Conclusion: Movement disorders are common in AE and their identification, in conjunction with other clinical and paraclinical features, may facilitate earlier diagnosis. The prognostic implications of movement disorders in AE warrant further dedicated study. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Anti-N-methyl-D-aspartate (NMDA) receptor antibody (anti-NMDAR Ab)-mediated encephalitis is an autoimmune disorder involving the production of antibodies against NMDARs in the central nervous system that leads to neurological or psychiatric dysfunction. Initially described as a paraneoplastic syndrome in young women with teratomas, increased testing has found it to be a heterogeneous condition that affects both the sexes with varying clinical manifestations, severity, and aetiology. This case report describes a 67-year-old man with a 40-year history of relapsing, severe, treatment-refractory schizophrenia. Due to the worsening of his condition during a prolonged inpatient admission for presumed relapse of psychosis, a revisit of the original diagnosis was considered with extensive investigations performed including an autoimmune panel. This revealed anti-NMDAR Abs in both the serum and cerebrospinal fluid on two occasions. Following treatment with intravenous immunoglobulin and methylprednisolone, he demonstrated rapid symptom improvement. This is a rare case of a long-standing psychiatric presentation with a preexisting diagnosis of schizophrenia subsequently found to have anti-NMDAR Ab-mediated encephalitis. Whether the case is one of initial NMDAR encephalitis vs. overlap syndrome is unknown. Most importantly, this case highlights the need for vigilance and balanced consideration for treatment in cases of long-standing psychiatric presentation where the case remains treatment refractory to antipsychotics or when atypical features including seizures and autonomic dysfunction or focal neurology are observed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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. Highlights • This review examines predictive variables of prognosis in autoimmune encephalitis. • Delayed immunotherapy is associated with a wide variety of poor outcomes. • Some variables had clear associations with outcomes only in anti-NMDAR encephalitis. • The associations of several other variables with outcomes are unclear. [ABSTRACT FROM AUTHOR]

Autoimmune encephalitis (AE) is an inflammatory disease of the central nervous system which can result in long-term seizures and cognitive dysfunction despite treatment with immunotherapy. The role of the innate immune system in AE is not well established. To investigate the contribution of innate immunity to AE and its long-term outcomes we evaluated peripheral monocytes and serum cytokines in the periphery of patients with AE. We recruited 40 patients with previously diagnosed AE and 28 healthy volunteers to our cross-sectional observation study and evaluated their peripheral blood monocytes via flow cytometry and serum cytokines (CCL-2, CCL-17, G-CSF, GM-CSF, IFNγ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, TNFα) via ELISA.Compared with controls the AE cohort had expansion of the 'pro-inflammatory' CD14+CD16+ monocyte sub-population (7.13% vs 5.46%, p < 0.01) with higher levels of serum IL-6 (2.34 pg/mL vs 0.54 pg/mL, p < 0.001). These changes were most significant in anti -LGI-1 antibody mediated AE, an AE subtype with poor long-term cognitive outcomes. Expansion of the peripheral CD14+CD16+ monocyte population and increased serum IL-6 in AE is reflective of changes seen in other systemic inflammatory and neurodegenerative conditions. These changes may indicate a persistent pro-inflammatory state in AE and may contribute to poor long-term outcomes. • Pro-inflammatory peripheral monocytes are increased in autoimmune encephalitis. • IL-6 is also elevated in the serum despite treatment with immunotherapy. • Changes in inflammatory biomarkers are most marked in the LGI-1 autoimmune encephalitis subset. [ABSTRACT FROM AUTHOR]

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. • Autoimmune encephalitis (AE) can manifest with a wide spectrum of psychiatric presentations developing over days to months. • Accompanying neurologic symptoms may develop simultaneously, sequentially or after a prolonged period of psychiatric symptoms. • The pathophysiology of AE and brain regional inflammation can explain some of the psychiatric manifestations. • For early disease identification, understanding red flags which may indicate an autoimmune process is imperative. • The overlap between psychiatry and neurology in autoimmune encephalitis requires a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

• The prevalence of drug-resistant epilepsy (DRE) in autoimmune encephalitis (AIE) is 16%. • Status epilepticus is a significant risk factor for the development of DRE. • Abnormalities on the EEG are highly prevalent in patients with AIE who develop DRE. • The presence of periodic discharges and temporal lobe abnormalities on EEG can predict the onset of DRE in AIE. To evaluate the prevalence and biomarkers of drug-resistant epilepsy (DRE) in patients with autoimmune encephalitis (AIE). Sixty-nine patients with AIE were recruited retrospectively and electroencephalographies (EEGs) were reviewed using a standard reporting proforma. Associations between EEG biomarkers and DRE development at 12 months were examined using logistic regression modeling and were utilized to create a DRE risk score. Sixteen percent of patients with AIE developed DRE at 12-month follow-up. The presence of status epilepticus (SE) (OR 11.50, 95% CI [2.81, 51.86], p -value <0.001), temporal lobe focality (OR 9.90, 95% CI [2.60, 50.71], p -value 0.001) and periodic discharges (OR 19.12, 95% CI [3.79, 191.10], p -value 0.001) on the admission EEG were associated with the development of DRE at 12 months. These variables were utilized to create a clinically applicable risk score for the prediction of DRE development. Drug-resistant epilepsy is an infrequent complication of AIE. Electroencephalography changes during the acute illness can predict the risk of DRE at 12 months post-acute AIE. The identified EEG biomarkers provide the basis to generate a clinically applicable prediction tool which could be used to inform treatment, prognosis, and select patients for acute treatment trials. [ABSTRACT FROM AUTHOR]

• Autoimmune encephalitis is a rare illness that commonly presents with seizures. • Electroencephalography can provide diagnostic and prognostic information in AIE. • Different AIE subtypes show unique characteristics on EEG to aid early diagnosis. • Abnormal EEG background was associated with outcome at discharge and 12 months. To evaluate the utility of electroencephalography (EEG) changes as diagnostic and prognostic biomarkers in acute autoimmune encephalitis (AIE). 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. 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). 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. [ABSTRACT FROM AUTHOR]

To examine the prognostic value of CSF abnormalities in seropositive autoimmune encephalitis (AE). We retrospectively studied 57 cases of seropositive AE. Primary outcomes were mortality and modified Rankin Scale, while secondary outcomes were first line treatment failure, ICU admission and relapse. Regression analysis was performed. CSF white cell count (WCC) was higher in the NMDAR group, while elevated protein was more common amongst other subtypes. We found an association between WCC >5 cells/mm3 and treatment failure (OR 16.0, p = 0.006)), and between WCC >20 cells/mm3 and ICU admission (OR 19.3, p = 0.026). Different subsets of AE have characteristic CSF abnormalities, which may aid recognition during early evaluation. CSF WCC had prognostic significance in our study. [Display omitted] • CSF analysis is a critical diagnostic step in evaluation of autoimmune encephalitis. • CSF abnormalities are characteristic for different seropositive subtypes. • CSF pleocytosis was associated with ICU admission and treatment failure. [ABSTRACT FROM AUTHOR]