Autoimmune Encephalitis Patients Research Articles

Clinical features, cerebrospinal fluid changes, and prognosis in Chinese patients with autoimmune encephalitis.

Autoimmune encephalitis (AE) is a rare, treatable disease of the central nervous system (CNS) caused by an antibody-related immune response. This study is to investigate the correlation of clinical features, cerebrospinal fluid (CSF) characteristics, and prognosis in patients with AE. A total of 71 patients diagnosed with antibody-positive AE were retrospectively analyzed. The patients were divided into three groups: anti-NMDAR group, anti-LGI1 group, and other types. Clinical data were collected to analyze clinical features and CSF results, and prognosis was determined by modified Rankin Scale (mRS). There was statistical difference in the incidences of decreased consciousness level (P < 0.001), memory loss (P = 0.017), speech disorders (P = 0.035), and dyskinesia (P = 0.001) in different antibodies groups. Younger age (P = 0.018), elevated CSF chloride content (P = 0.006), and white blood cells > 50/mm3 (P = 0.026) were highly correlated with ICU admission. Anti-LGI1 encephalitis had a relatively small risk for ICU admission (P = 0.034), and a lower risk of poor functional recovery (P = 0.048) and recurrence (P = 0.041). Patients with first-line treatment failure (P = 0.021) had an increased risk of poor functional recovery. Delayed treatment (P = 0.011) would increase the risk of recurrence. There are differences in age, gender, clinical characteristics, and CSF results in different subtypes of AE. First-line therapy failure would have poor functional recovery, and delayed therapy would increase the risk of relapse. Chloride ion content and white blood cell count in cerebrospinal fluid are positively correlated with the patient's exacerbation and admission to ICU. These indicators have certain clinical value for the prognosis of AE patients.

Seizures as Initial Presentation and Enduring Predisposition to Seizures in Autoimmune Encephalitis

Purpose. This retrospective study is aimed at investigating the clinical characteristics of autoimmune encephalitis (AE) and long-term prognosis of patients who initially present with seizures as well as risk factors for enduring predisposition to seizures in AE. Methods. From January 1, 2013, to October 31, 2021, a total of 343 AE patients from a single center diagnosed with autoimmune encephalitis (AE) were enrolled in this study, including 198 antibody-positive AE and 145 antibody-negative but probable AE. According to initial symptoms, AE patients were divided into two groups: onset with seizure group and onset with nonseizure group. The clinical characteristics were retrospectively reviewed. Patients were clinically evaluated at onset and at 6, 12, and 24 months of follow-up. Modified Rankin Scale (MRS) score, Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score, and seizure-related information were assessed. Results. In AE, patients with seizures as the first presentation were younger, with a median-onset age of 28 years old. Compared with other types of antibody-positive AE, anti-GABABR AE more frequently began with seizures, while anti-CASPR2, anti-AMPAR, and anti-DPPX encephalitis usually began with symptoms other than seizures. The most common type of initial seizures in AE was focal to bilateral seizure (67.6%), with a significant prevalence in antibody-positive AE (P=0.001). In addition, compared with nonseizure group, patients with seizures as an initial presentation had higher MRS and CASE scores at 24 months of follow-up. Older age at onset and focal nonmotor seizure type were independent risk factors for an enduring predisposition to seizures in AE patients. Conclusion. The younger and anti-GABABR-positive AE patients are more prone to onset with seizures. AE patients who initially presented with seizures had worse long-term neurological recovery. Onset age and seizure type should be highly appreciated when formulating the strategy for therapy at post-AE status.

B-cell targeted therapies in autoimmune encephalitis: mechanisms, clinical applications, and therapeutic potential.

Autoimmune encephalitis (AE) broadly refers to inflammation of the brain parenchyma mediated by autoimmune mechanisms. In most patients with AE, autoantibodies against neuronal cell surface antigens are produced by B-cells and induce neuronal dysfunction through various mechanisms, ultimately leading to disease progression. In recent years, B-cell targeted therapies, including monoclonal antibody (mAb) therapy and chimeric antigen receptor T-cell (CAR-T) therapy, have been widely used in autoimmune diseases. These therapies decrease autoantibody levels in patients and have shown favorable results. This review summarizes the mechanisms underlying these two B-cell targeted therapies and discusses their clinical applications and therapeutic potential in AE. Our research provides clinicians with more treatment options for AE patients whose conventional treatments are not effective.

Quantitative brain 18F-FDG PET/CT analysis in seronegative autoimmune encephalitis.

Brain 18F-FDG PET/CT is a useful diagnostic in evaluating patients with suspected autoimmune encephalitis (AE). Specific patterns of brain dysmetabolism have been reported in anti-NMDAR and anti-LGI1 AE, and the degree of dysmetabolism may correlate with clinical functional status.18FDG-PET/CT abnormalities have not yet been described in seronegative AE. We conducted a cross-sectional analysis of brain18FDG-PET/CT data in people with seronegative AE treated at the Johns Hopkins Hospital. Utilizing NeuroQ™ software, the Z-scores of 47 brain regions were calculated relative to healthy controls, then visually and statistically compared for probable and possible AE per clinical consensus diagnostic criteria to previous data from anti-NMDAR and anti-LGI1 cohorts. Eight probable seronegative AE and nine possible seronegative AE were identified. The group only differed in frequency of abnormal brain MRI, which was seen in all of the probable seronegative AE patients. Both seronegative groups had similar overall patterns of brain dysmetabolism. A common pattern of frontal lobe hypometabolism and medial temporal lobe hypermetabolism was observed in patients with probable and possible seronegative AE, as well as anti-NMDAR and anti-LGI1 AE as part of their respective characteristic patterns of dysmetabolism. Four patients had multiple brain18FDG-PET/CT scans, with changes in number and severity of abnormal brain regions mirroring clinical status. A18FDG-PET/CT pattern of frontal lobe hypometabolism and medial temporal lobe hypermetabolism could represent a common potential biomarker of AE, which along with additional clinical data may facilitate earlier diagnosis and treatment.

Language impairments in seropositive and seronegative autoimmune encephalitis.

Autoimmune encephalitis (AE) is a rare neuroinflammatory disease affecting the central nervous system. To examine language functions in patients with different subsets of AE consisting of seropositive and seronegative groups. Fifty-two patients were recruited from neurology departments in Melbourne, Australia, who met clinical criteria for possible AE. Language tests include the Naming Test from the Sydney Language Battery (SydBat), the semantic fluency trial from the Controlled Oral Word Association Test (COWAT), and the Vocabulary and Similarities subtests of the Weschler Abbreviated Scale of Intelligence-Second Edition. The results were standardised with normative data. The mean age of our cohort was 52.5years old, with the average time from hospital admission to recruitment being 38.41months. At an aggregate level, none of the mean language test z-scores were below normative data. At the patient level, impairment rates were 18.37% for COWAT (animals), 28.57% for SydBat (naming), 4.65% for Similarities, and 4.55% for Vocabulary. Chi-squared goodness of fit tests indicated that observed performances were significantly below expected performances for the SydBat (naming) test (p < 0.0001) and COWAT (animals) (p = 0.004). While, on average, language functions were within normal limits in patients with AE, but a subgroup exhibited lower performance in semantic fluency and visual confrontation naming, with impairment rates below expected norms. To advance understanding of language in chronic AE patients, exploring the impact of seizure burden, antiseizure medication use, and the relationship of language functions with other cognitive functions is crucial.

Association between red blood cell distribution width-to-albumin ratio and the prognosis in patients with autoimmune encephalitis: a retrospective cohort study.

Red blood cell distribution width-to-albumin ratio (RAR) is a combined new indicator reflecting immunology and has been reported to predict the prognosis of inflammation-related diseases and brain diseases. However, the association and predictive value of RAR in the prognosis of patients with autoimmune encephalitis (AE) has not been reported. This was a retrospective cohort study, and data were collected from the Henan Provincial People's Hospital. RAR was categorized according to quartile. The prognosis was assessed using the modified Rankin Scale (mRS), and an mRS score of ≥3 was defined as a poor prognosis. The logistical regression model was used to explore the association between RAR and the prognosis, with results reported as odds ratio (OR) and 95% confidence interval (CI). The predictive value of RAR was evaluated by calculating the area under the receiving operating curve (AUC), sensitivity, specificity, and accuracy. A total of 175 eligible patients were included for analysis, and 51 patients were identified as having poor prognosis. After adjusting age, cancer, other diseases, histological subtype, antiepileptic therapy, anti-tumor treatment, ICU treatment, and length of stay, RAR in the highest quartile (Q4) was found to be significantly associated with the high odds of poor prognosis (OR = 5.63, 95%CI: 1.98-16.02) compared to RAR in the lowest quartile (Q1). In addition, RAR was identified as a predictor for the prognosis of AE patients (AUC = 0.660, 95%CI: 0.574-0.746). This study found the close association and predictive value of RAR for the prognosis of AE patients, indicating that RAR might help clinicians identify high-risk populations.

Criminality in patients with autoimmune encephalitis: A case series.

Despite it being an immunotherapy-responsive neurological syndrome, patients with autoimmune encephalitis (AE) frequently exhibit residual neurobehavioural features. Here, we report criminal behaviours as a serious and novel postencephalitic association. This retrospective cohort study included 301 AE patients. Five of who committed crimes underwent direct assessments and records review alongside autoantibody studies. Five of 301 patients (1.7%) with AE exhibited criminal behaviours, which included viewing child pornography (n = 3), repeated shoplifting, and conspiracy to commit murder. All five were adult males, with LGI1 autoantibodies (n = 3), CASPR2 autoantibodies, or seronegative AE. None had evidence of premorbid antisocial personality traits or psychiatric disorders. Criminal behaviours began a median of 18 months (range = 15 months-12 years) after encephalitis onset. At the time of crimes, two patients were immunotherapy-naïve, three had been administered late immunotherapies (at 5 weeks-4 months), many neurobehavioural features persisted, and new obsessive behaviours had appeared. However, cognition, seizure, and disability measures had improved, alongside reduced autoantibody levels. Criminal behaviours are a rare, novel, and stigmatizing residual neurobehavioural phenotype in AE, with significant social and legal implications. With caution towards overattribution, we suggest they occur as part of a postencephalitis limbic neurobehavioural syndrome.

Risk Prediction Models for Invasive Mechanical Ventilation in Patients with Autoimmune Encephalitis: A Retrospective Cohort Study

Background and Objectives. Timely identification of developing severe respiratory failure in patients with autoimmune encephalitis (AE) is crucial to ensure prompt treatment with invasive mechanical ventilation (IMV), which can potentially improve the outcome. We aimed to develop a nomogram for requiring IMV based on easily available clinical characteristics. Methods. A multivariate predictive nomogram model was developed using the risk factors identified by LASSO regression and assessed by receiver operator characteristics (ROC) curve, calibration curve, and decision curve analysis. Results. The risk factors predictive of severe respiratory failure were male gender, impaired hepatic function, elevated intracranial pressure, and higher neuron-specific enolase. The final nomogram achieved an AUC of 0.770. After validation by bootstrapping, a concordance index of 0.748 was achieved. Conclusions. Our nomogram accurately predicted the risk of developing respiratory failure needing IMV in AE patients and provide clinicians with a simple and effective tool to guide treatment interventions in the AE patients.

Antibody induced seizure susceptibility and impaired cognitive performance in a passive transfer rat model of autoimmune encephalitis.

Autoimmune encephalitis (AE) is a distinct neuro-immunological disorder associated with the production of autoantibodies against neuronal proteins responsible for pharmacoresistant seizures, cognitive decline and behavioral problems. To establish the causal link between leucine-rich glioma inactivated 1 (LGI1) antibody and seizures, we developed an in-vivo antibody-mediated AE rat model in which serum antibodies (IgG) obtained from blood samples of leucine-rich glioma inactivated 1 (LGI1) protein antibody (IgG) positive encephalitis patients were passively transferred into non-epileptic Wistar rats. Serum IgG of N-methyl-d-aspartate receptor (NMDAR) antibody positive patients were used as positive control since the pathogenicity of this antibody has been previously shown in animal models. Total IgG obtained from the pooled sera of NMDAR and LGI1-IgG positive patients with epileptic seizures and healthy subjects was applied chronically every other day for 11 days into the cerebral lateral ventricle. Spontaneous seizure development was followed by electroencephalography. Behavioral tests for memory and locomotor activity were applied before and after the antibody infusions. Then, pentylenetetrazol (PTZ) was administered intraperitoneally to evaluate seizure susceptibility. Immunohistochemistry processed for assessment of hippocampal astrocyte proliferation and expression intensity of target NMDAR and LGI1 antigens. No spontaneous activity was observed during the antibody infusions. PTZ-induced seizure stage was significantly higher in the NMDAR-IgG and LGI1-IgG groups compared to control. Besides, memory deficits were observed in the NMDAR and LGI1-IgG groups. We observed enhanced astrocyte proliferation in NMDAR- and LGI1-IgG groups and reduced hippocampal NMDAR expression in NMDAR-IgG group. These findings suggest that neuronal surface auto-antibody administration induces seizure susceptibility and disturbed cognitive performance in the passive transfer rat model of LGI1 AE, which could be a potential in-vivo model for understanding immune-mediated mechanisms underlying epileptogenesis and highlight the potential targets for immune-mediated seizures in AE patients.

Cerebral glucose hypometabolism and hypoperfusion of cingulate gyrus: an imaging biomarker of autoimmune encephalitis with psychiatric symptoms

BackgroundAbout 60% of autoimmune encephalitis (AE) patients present psychiatric symptoms, but the underlying mechanism remains unknown. This study examined the role of the cingulate cortex in such patients to identify predictive poor psychiatric factors.MethodsIn this study, 49 AE patients and 39 healthy controls were enrolled. AE patients were further divided into two groups based on the presence/absence of psychiatric symptoms. The ratio of the standardized uptake value (SUVR) and relative cerebral blood flow (rCBF) in different regions of the cingulate cortex were calculated through positron emission tomography–computed tomography (PET/CT) and arterial spin labeling (ASL) MRI, and the results were compared among the three groups. In addition, we followed-up on the psychiatric outcomes and identified the risk factors for poor psychiatric prognosis, focusing on the cingulate cortex.ResultsMore than half of the AE patients (27/49) exhibited psychiatric symptoms. Agitation and thought blocking were typical psychiatric phenotypes, except for anti-glutamic acid decarboxylase 65 (GAD65) encephalitis, which mainly presented with catatonia and a depressed mood. AE patients with psychiatric symptoms experienced reduced metabolism and perfusion of the anterior cingulate cortex (ACC), midcingulate cortex (MCC), and posterior cingulate cortex (PCC). The SUVR of ACC can be used as an independent risk factor of poor psychiatric outcomes, which had an area under the ROC curve (AUC) of 0.865.ConclusionImpaired cingulate cortex function in AE may be the potential mechanism of psychiatric symptoms. Hypometabolism of ACC is an independent prognostic factor predicting an unfavorable psychiatric prognosis in AE.

Antibody-Negative Autoimmune Encephalitis: A Single-Center Retrospective Analysis.

Autoimmune encephalitis (AE) refers to a heterogenous group of inflammatory CNS diseases. Subgroups with specified neural autoantibodies are more homogeneous in presentation, trigger factors, outcome, and response to therapy. However, a considerable fraction of patients has AE features but does not harbor detectable autoantibodies and is referred to as antibody-negative AE. Our aim was to describe clinical features, trigger factors, treatments, and outcome of a cohort of comprehensively tested antibody-negative AE patients. This retrospective monocentric study recruited adult patients whose serum and/or CSF was sent to our tertiary center for neural antibody testing between 2011 and 2020, who entered the diagnostic algorithm as possible antibody-negative AE and had the following: (1) probable antibody-negative AE, definite antibody-negative acute disseminated encephalomyelitis (ADEM), or definite autoimmune limbic encephalitis (LE) according to diagnostic criteria; (2) available data on MRI of the brain, CSF, and EEG; and (3) stored serum and/or CSF samples. These samples were reanalyzed using a comprehensive combination of cell-based and tissue-based assays. Of 2,250 patients tested, 33 (1.5%) were classified as possible antibody-negative AE. Of these, 5 were found to have antibodies by comprehensive testing, 5 fulfilled the criteria of probable AE (3F:2M, median age 67, range 42-67), 4 of definite autoimmune LE (2F:2M, median age 45.5, range 27-60 years), one of definite antibody-negative ADEM, 2 of Hashimoto encephalopathy, one had no samples available for additional testing, and 15 had no further categorization. Of 10 probable/definite AE/LE/ADEM, one had a malignancy and none of them received an alternative diagnosis until the end of follow-up (median 18 months). In total, 80% (8/10) of patients received immunotherapy including corticosteroids, and 6/10 (60%) patients received rituximab, azathioprine, cyclophosphamide, plasma exchange, or IV immunoglobulins. Five (50%) patients improved, one (10%) stabilized, one (10%) worsened, and 3 (30%) died. All deaths were considered to be related to encephalitis. We did not observe differences of immunotherapy-treated patients in likelihood of improvement with or without nonsteroidal immunotherapy (with 2/6, without 1/2). Antibody-negative AE should be diagnosed only after comprehensive testing. Diagnostic effort is important because many patients benefit from immunotherapy and some have malignancies.

Characterizing cognitive function in patients with autoimmune encephalitis: an Australian prospective study

ObjectiveThis study uses the Wechsler intelligence and memory scales to characterize the cognitive function of patients with autoimmune encephalitis (AE) in the chronic stage of the disease. AE is a group of neuroinflammatory disorders, and cognitive impairment is a significant source of chronic morbidity in these patients.MethodsFifty patients with an average disease duration of 3.2 years after diagnosis were prospectively recruited from four hospitals. They underwent a comprehensive cognitive examination using the Wechsler Abbreviated Scale of Intelligence (WASI-II), Wechsler Adult Intelligence Scale (WAIS-IV) and Wechsler Memory Scale (WMS-IV). Summary statistics were computed, and single-sample and independent-samples t tests were used to compare the cohort to normative data.ResultsThe results revealed significantly reduced performances in perceptual reasoning, processing speed, and working memory among AE patients. Seropositive AE patients exhibited below-norm processing speed, while the seronegative group showed reduced working memory and processing speed. Delayed memory performance was significantly below expectations only in seronegative patients. Pattern analysis indicated that intact cognition was the most observed outcome after AE, but significant heterogeneity was observed among the impaired patients.ConclusionsThe study identified deficits in perceptual reasoning, processing speed, and working memory among chronic AE patients. Pattern analysis highlighted positive long-term cognitive outcomes for many but varied outcomes for those with ongoing difficulties. Although severely cognitively impaired patients were not included, the findings apply to AE cohorts who attend outpatient clinical neuropsychology consultations emphasizing the need for thorough cognitive assessment. The results suggest a need for further research targeting other cognitive domains, including executive functions.

Heterogeneity of clinical features, EEG and brain imaging findings in anti-leucine-rich glioma-inactivated protein 1 autoimmune encephalitis: a retrospective case series study and review of the literature

BackgroundAnti-leucine-rich glioma-inactivated 1 (LGI-1) autoimmune encephalitis (AE), characterized by rapid decline of memory, seizures, and neuropsychiatric abnormalities, is a rare but devastating disorder. Early diagnosis and treatment are essential to prevent long-term sequelae. In this report, we provide a detailed description of clinical characteristics, laboratory test results, imaging, and electroencephalography (EEG) findings, as well as treatment responses of eight patients with anti-LGI-1 AE treated at our center.Case presentationAt the onset, all eight patients presented with confusion/memory deterioration, seizures (including faciobrachial dystonic seizures or other types of seizure), and behavioral changes such as hallucination, paranoia, and anxiety. Four patients were found with severe hyponatremia. Anti-LGI1 antibodies were detected in the cerebrospinal fluid and/or serum of all patients. For patients with faciobrachial dystonic seizures, no discernible scalp EEG change was detected, while EEG recording of patients experiencing other types of seizure showed focal slowing, focal epileptiform discharges, and focal onset seizures. All patients showed abnormal brain magnetic resonance imaging signals, mainly involving the mesial temporal lobe and the hippocampus. In addition, one patient also experienced fulminant cerebral edema during the acute phase of the illness. All patients received immunotherapy and anti-seizure medications and achieved good seizure control. Nevertheless, these patients continued to experience cognitive impairment during their long-term follow-ups.ConclusionsThe care of anti-LGI1 AE patients requires rapid evaluation, prompt initiation of immunotherapy, and long-term follow-up. The long-term presence of neurocognitive complications observed in these patients underline the importance of developing reliable biomarkers that can distinguish between different subtypes of this disease with heterogeneous clinico-electrographico-radiological features. Further research is needed to understand the molecular mechanisms underlying the heterogeneity, in order to facilitate development of more effective treatments for anti-LGI1 AE.

Gastrodin Improves Quality of Life and Outcome of Autoimmune Encephalitis Treatment with High-Dose Gamma Globulin and Collaborative Care

This study aims to elucidate the effectiveness of gastrodin in improving the outcome of autoimmune encephalitis patients receiving high-dose gamma globulin plus collaborative nursing care. Gastrodin led to higher post-treatment Mini-mental State Examination scores, CD3+, CD4+, IgA, IgG, and IgM than the control group, and lower inflammatory cytokine levels (P &lt; 0.05). To sum up, gastrodin administration to patients receiving high-dose gamma globulin and collaborative nursing care was highly effective in treating autoimmune encephalitis and can effectively improve patients’ quality of life.

Validating Prediction Tools for Autoimmune Encephalitis in Adult Taiwanese Patients: A Retrospective Study.

Autoimmune encephalitis (AE) is a neurological emergency. We aimed to analyze the application and effectiveness of the currently available prediction tools for AE patients in Taiwan. We retrospectively collected 27 AE patients between January 2008 and December 2019. Antibody Prevalence in Epilepsy (APE) score, Response to Immunotherapy in Epilepsy (RITE) score, and anti-NMDAR Encephalitis One Year Functional Status (NEOS) score were applied to validate their usability. Based on the defined cutoff values, the sensitivity and specificity of each score were calculated. A receiver operating characteristic (ROC) curve and the area under the curve (AUC) were generated for each scoring system. The AUC value of APE was 0.571. The AUC value of RITE was 0.550. The AUC values for the NEOS score at discharge and long-term follow-up were 0.645 and 0.796, respectively. The performance of APE and RITE scores was suboptimal in the Taiwanese cohort, probably due to the limitations of the small sample size and single ethnicity. On the other hand, the NEOS score performed better on long-term follow-up than at discharge.

The micro and macro interactions in acute autoimmune encephalitis: a study of resting-state EEG.

Early recognition of autoimmune encephalitis (AIE) is often difficult and time-consuming. Understanding how the micro-level (antibodies) and macro-level (EEG) couple with each other may help rapidly diagnose and appropriately treat AIE. However, limited studies focused on brain oscillations involving micro- and macro-interactions in AIE from a neuro-electrophysiological perspective. Here, we investigated brain network oscillations in AIE using Graph theoretical analysis of resting state EEG. AIE Patients (n = 67) were enrolled from June 2018 to June 2022. Each participant underwent a ca.2-hour 19-channel EEG examination. Five 10-second resting state EEG epochs with eyes closed were extracted for each participant. The functional networks based on the channels and Graph theory analysis were carried out. Compared with the HC group, significantly decreased FC across whole brain regions at alpha and beta bands were found in AIE patients. In addition, the local efficiency and clustering coefficient of the delta band was higher in AIE patients than in the HC group (P < 0.05). AIE patients had a smaller world index (P < 0.05) and higher shortest path length (P < 0.001) in the alpha band than those of the control group. Also, the AIE patients' global efficiency, local efficiency, and clustering coefficients decreased in the alpha band (P < 0.001). Different types of antibodies (antibodies against ion channels, antibodies against synaptic excitatory receptors, antibodies against synaptic inhibitory receptors, and multiple antibodies positive) showed distinct graph parameters. Moreover, the graph parameters differed in the subgroups by intracranial pressure. Correlation analysis revealed that magnetic resonance imaging abnormalities were related to global efficiency, local efficiency, and clustering coefficients in the theta, alpha, and beta bands, but negatively related to the shortest path length. These findings add to our understanding of how brain FC and graph parameters change and how the micro- (antibodies) scales interact with the macro- (scalp EEG) scale in acute AIE. The clinical traits and subtypes of AIE may be suggested by graph properties. Further longitudinal cohort studies are needed to explore the associations between these graph parameters and recovery status, and their possible applications in AIE rehabilitation.

Therapy response in seronegative versus seropositive autoimmune encephalitis.

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. An electronic database search retrospectively identified 150AE 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). 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. Since both, patients with seronegative and seropositive AE, substantially benefitted from immunotherapies, these should be considered in AE patients irrespective of their antibody results.

A novel classification model based on cerebral 18F-FDG uptake pattern facilitates the diagnosis of acute/subacute seropositive autoimmune encephalitis

PurposeTo explore the intrinsic alteration of cerebral 18F-FDG metabolism in acute/subacute seropositive autoimmune encephalitis (AE) and to propose a universal classification model based on 18F-FDG metabolic patterns to predict AE. MethodsCerebral 18F-FDG PET images of 42 acute/subacute seropositive AE patients and 45 healthy controls (HCs) were compared using voxelwise and region of interest (ROI)-based schemes. The mean standardized uptake value ratios (SUVRs) of 59 subregions according to a modified Automated Anatomical Labeling (AAL) atlas were compared using a t-test. Subjects were randomly divided into a training set (70%) and a testing set (30%). Logistic regression models were built based on the SUVRs and the models were evaluated by determining their predictive value in the training and testing sets. ResultsThe 18F-FDG uptake pattern in the AE group was characterized by increased SUVRs in the brainstem, cerebellum, basal ganglia, and temporal lobe, and decreased SUVRs in the occipital, and frontal regions with voxelwise analysis (false discovery rate [FDR] p<0.05). Utilizing ROI-based analysis, we identified 15 subareas that exhibited statistically significant changes in SUVRs among AE patients compared to HC (FDR p<0.05). Further, a logistic regression model incorporating SUVRs from the calcarine cortex, putamen, supramarginal gyrus, cerebelum_10, and hippocampus successfully enhanced the positive predictive value from 0.76 to 0.86 when compared to visual assessments. This model also demonstrated potent predictive ability, with AUC values of 0.94 and 0.91 observed for the training and testing sets, respectively. ConclusionsDuring the acute/subacute stages of seropositive AE, alterations in SUVRs appear to be concentrated within physiologically significant regions, ultimately defining the general cerebral metabolic pattern. By incorporating these key regions into a new classification model, we have improved the overall diagnostic efficiency of AE.

Cognitive Impairment is Associated with Longitudinal Disability in LGI-1-IgG Encephalitis (S22.007)

<h3>Objective:</h3> To determine predictors of longitudinal clinical outcomes in leucine-rich glioma inactivated-1 immunoglobulin G (LGI-1)-IgG autoimmune encephalitis (AE). <h3>Background:</h3> Longitudinal studies prognosticating outcomes in LGI-1-IgG AE are needed to identify key drivers of disability. We examine disability utilizing modified Rankin Scale (mRS) and an AE specific scale, the clinical assessment scale in AE (CASE). <h3>Design/Methods:</h3> A retrospective observational study of seropositive LGI-1-IgG AE patients was conducted between 2013–2022. Clinical predictors included demographics, clinical and paraclinical data, magnetic resonance imaging (MRI), and Montreal Cognitive Assessment (MoCA). Clinical outcomes included mRS and CASE scores. Logistic and linear regressions were used for modeling mRS and CASE, respectively. Baseline clinical characteristics were included as independent variables in the regression models. <h3>Results:</h3> Thirty patients (60% male, median age=69.5; IQR=63.0–76.0) were included, with a median follow-up time of 8.7 months (IQR=4.3–24.1). Seizures (29, [96.7%]), and cognitive impairment (CI) (30, [100%]) were present in the majority. Median initial MoCA was 23/30 (IQR=21.0–25.0). The majority received acute immunotherapy (27, [90%]), and maintenance immunotherapy, (26 [86.7%]). Baseline mRS (median=2.0, IQR=2.0–3.0) and CASE (mean=4.3, SD=3.7) correlated with each other (<i>r</i>=0.58, <i>P</i>&lt;.001) and with initial MoCA score (mRS <i>r</i>=−0.60, <i>P</i>=.009, CASE <i>r</i>=−0.51, <i>P</i>=.031). After 12 months from symptom onset, mRS (OR=0.88, [CI=0.82–0.94], <i>P</i>&lt;.001) and CASE (β=−0.03, [SE=0.01], <i>P</i>&lt;.001) decreased significantly. Temporal lobe(s) Fluid Attenuation Inversion Recovery (FLAIR) hyperintensity correlated with higher mRS longitudinally (OR=17.49, [CI=2.37, 129.05], <i>P</i>=.005). Higher initial MOCA was associated with lower mRS (OR=0.66, [CI=0.45–0.98], <i>P</i>=.04) and CASE (β=−0.24, [SE=0.13], <i>P</i>=.061) longitudinally. At last follow-up, most patients had ongoing cognitive symptoms (25, [83.3%]), while few had ongoing seizure activity (3, [10%]). <h3>Conclusions:</h3> CI is associated with disability at baseline and long-term follow up, underscoring cognition as an important determinant of disability outcomes in LGI-1-IgG AE. Severity of CI on baseline MoCA may offer prognostic information on long-term disability. <b>Disclosure:</b> Dr. Aboseif has a non-compensated relationship as a AAN Autoimmune Neurology Section -- Education Workgroup with AAN that is relevant to AAN interests or activities. Ms. Li has nothing to disclose. Dr. Amin has nothing to disclose. Brittany Lapin has received personal compensation for serving as an employee of Cleveland Clinic. Brittany Lapin has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Quality of Life Research. Brittany Lapin has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Anesthesia and Analgeisa. Dr. Abbatemarco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Abbatemarco has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Abbatemarco has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech . The institution of Dr. Abbatemarco has received research support from Horizon. Dr. Rae-Grant has received publishing royalties from a publication relating to health care. Dr. Rae-Grant has received publishing royalties from a publication relating to health care. Dr. Punia has nothing to disclose. Rachel Galioto has nothing to disclose. Dr. Kunchok has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Kunchok has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon therapeutics . Dr. Kunchok has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology.

Associations of Serum Neurofilament Light Chain with Outcomes in Children with Autoimmune Encephalitis (P4-5.009)

<h3>Objective:</h3> To examine associations between serum neurofilament light chain (sNfL) levels at disease onset with markers of clinical severity in children with autoimmune encephalitis (AE). <h3>Background:</h3> Despite significant advances in the diagnosis and treatment of AE, little is known about markers of disease severity and their associations with outcomes. sNfL, a marker of axonal destruction, may fill this gap. <h3>Design/Methods:</h3> This is a longitudinal prospective case-control study of children presenting to a single tertiary center with AE (n=48) vs. an age-matched healthy control population (HC) (n=88). Clinical data and modified Rankin Scale (mRS) scores were collected using a standard CRF at baseline and at follow-up, up to one year. sNfL levels in stored samples were measured by Single Molecule Array Immunoassay (SIMOA). Volumetric analyses of key anatomic structures of brain MRIs were performed using FreeSurfer. Diffusion weighted MRI was assessed for restricted diffusion. Following standard diagnostic criteria, children were classified into those with no biological marker (antibody or genetic) and those with. We further dichotomized children into high vs. low sNFL levels. Descriptive statistics, group differences, and correlational analyses were performed using JASP version 0.16.3. <h3>Results:</h3> Baseline sNfL levels were significantly higher in patients with AE (no Ab), AE (MOG), and ANEC vs. HCs (log₂ sNfL=4.3 AE(no Ab), 2.9 AE(NMDA), 5.6 AE(MOG), 6.3(ANEC), 2.4(HC), <i>p</i>&lt;0.001). AE patients in the high sNfL group were more likely to be admitted to the ICU (<i>p</i>=0.02) and had significantly higher mRS scores at nadir (<i>p</i>=0.04), compared to patients in the low sNfL group. However, there was no significant difference in mRS scores at follow-up between groups. Baseline sNfL correlated significantly with baseline restricted diffusion (r_s(43)=0.45, <i>p</i>=0.002) and thalamic volumes (r_s(31)=0.45, <i>p</i>=0.009). <h3>Conclusions:</h3> Baseline sNfL levels may serve as a marker of disease severity in patients with AE. Future studies are needed to evaluate their associations with long-term outcomes. <b>Disclosure:</b> Ms. Da Silva has nothing to disclose. Ms. Yea has nothing to disclose. Dr. AlYanbuaawy has nothing to disclose. Dr. Matt has nothing to disclose. Dr. Longoni has nothing to disclose. Helen Branson has nothing to disclose. Logi Vidarsson has nothing to disclose. An immediate family member of Dr. Ertl-Wagner has received personal compensation for serving as an employee of Siemens Healthineers. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for PRIME. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Dr. Yeh has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Yeh has received research support from Biogen. The institution of Dr. Yeh has received research support from Stem Cell Network. The institution of Dr. Yeh has received research support from CIHR. The institution of Dr. Yeh has received research support from Ontario Institute for Regenerative Medicine. The institution of Dr. Yeh has received research support from National MS Society. The institution of Dr. Yeh has received research support from NIH. The institution of Dr. Yeh has received research support from SickKids Foundation. The institution of Dr. Yeh has received research support from CMSC. The institution of Dr. Yeh has received research support from MSSC.