Type Of Autoimmune Encephalitis Research Articles

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.

Genetic predisposition to autoimmune encephalitis and paraneoplastic neurological syndromes.

We summarize the recent discoveries on genetic predisposition to autoimmune encephalitis and paraneoplastic neurological syndromes (PNS), emphasizing clinical and pathophysiological implications. The human leukocyte antigen (HLA) is the most studied genetic factor in autoimmune encephalitis and PNS. The HLA haplotype 8.1, which is widely known to be related to systemic autoimmunity, has been only weakly associated with a few types of autoimmune encephalitis and PNS. However, the strongest and most specific associations have been reported in a subgroup of autoimmune encephalitis that comprises antileucine-rich glioma-inactivated 1 (LGI1) limbic encephalitis, associated with DRB1∗07 : 01 , anticontactin-associated protein-like 2 (CASPR2) limbic encephalitis, associated with DRB1∗11 : 01 , and anti-IgLON5 disease, associated with DRB1∗10 : 01∼DQA1∗01∼DQB1∗05 . Non-HLA genes have been poorly investigated so far in autoimmune encephalitis, mainly in those lacking HLA associations such as anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, with only a few genome-wide association studies (GWAS) reporting equivocal results principally limited by small sample size. Genetic predisposition seems to be driven mostly by HLA in a group of autoimmune encephalitis characterized by being nonparaneoplastic and having predominantly IgG4 autoantibodies. The contribution of non-HLA genes, especially in those diseases lacking known or strong HLA associations, will require large cohorts enabling GWAS to be powerful enough to render meaningful results.

Red flags and symptom overlap in anti‐IgLON5 disease and dementia with Lewy bodies – a systematic review

AbstractBackgroundAnti‐IgLON5 disease is a rare but potentially reversible cause of cognitive impairment, sleep disturbances, dysautonomia, and movement disorders. It is a type of autoimmune encephalitis (AE) but unlike other AEs anti‐IgLON5 disease has an insidious onset and prominent tau pathology. Anti‐IgLON5 disease mimics neurodegenerative disorders and multiple symptoms overlap with the second most common cause of neurodegenerative dementia, Dementia with Lewy bodies (DLB). The purpose of this review was to assess the overlap in features between anti‐IgLON5 disease and DLB and to identify potential red flags for anti‐IgLON5 disease in patients undergoing diagnostic evaluation for DLB.MethodWe conducted a systematic review of reports on features of anti‐IgLON5 disease from full‐text articles in MEDLINE, Web of Science, and Embase. The reviewed data was compared to consensus criteria for DLB.ResultWe included 57 studies with a total of 125 cases of anti‐IgLON5 disease. The median age was 61 years at diagnosis, with a median symptom duration of 3.5 years. Ten % (13/113 cases) presented with cognitive dysfunction. REM‐sleep disorder was diagnosed in 43% (17/39 cases), and movement disorders were present in 73% (80/110 cases) of which parkinsonism was identified in 21% (18/85 cases). In 47% (25/59 cases), psychiatric disturbances were reported, and hallucinations were observed in 37% (11/30 cases). Dysautonomia was reported in 56% (42/75 cases). Regarding red flags for anti‐IgLON5 disease, bulbar symptoms were observed in 75% (82/109 cases) and respiratory insufficiency was in 60% (32/66 cases). Brain MRI was normal in 56% (40/72 cases) and routine cerebrospinal fluid examination was normal in 63% (36/57 cases). Anti‐IgLON5 antibodies were positive in serum in all cases, where serum was tested and positive in cerebrospinal fluid in 96% (71/75 cases).ConclusionWe found a significant overlap between symptoms in anti‐IgLON5 disease and DLB including cognitive dysfunction, REM‐sleep disorders, parkinsonism, and an insidious onset over several years. We propose that anti‐IgLON5 disease should be considered in atypical DLB cases with bulbar or respiratory symptoms. Our study contributes to the emerging knowledge on symptoms and biomarkers in anti‐IgLON5 disease.

Validation of different predictive scoring scales in patients with new-onset epileptic seizures or epilepsy related to neuronal surface antibody-mediated autoimmune encephalitis

ObjectiveTo validate the different predictive scoring scales in the Chinese population with new-onset epileptic seizures or epilepsy of unknown etiology related to neuronal surface antibody (Ab)-mediated autoimmune encephalitis (AE). MethodsWe retrospectively reviewed the charts of 174 consecutive patients from October 2018 to December 2022, whose serum and cerebrospinal fluid samples were tested for neuronal surface Abs. The antibody prevalence in epilepsy and encephalopathy (APE2), antibodies contributing to focal epilepsy signs and symptoms (ACES), “obvious” indications for neural antibody testing in epilepsy or seizures (ONES) checklist, and the combinations were used to validate the predictive models of neuronal surface Ab-mediated AE. ResultsA total of 139 patients with new-onset epileptic seizures or epilepsy of unknown etiology were enrolled. Abs were detected in 37 patients (26.6%). The APE2/ONES reflex score had the highest sensitivity (89.2%) and lowest specificity (41.7%). The ACES score had the lowest sensitivity (67.5%) and highest specificity (64.7%). Variations in the performance were observed in the different types of AE.100% of patients with anti-γ-aminobutyric acid B-B receptor encephalitis were predicted by ONES, APE2/ONES reflex, and ACES/ONES reflex scores. Only 75% of patients with anti-N-methyl-D-aspartate receptor encephalitis were predicted by the APE2/ONES and ACES/ONES reflex scores. ConclusionOur study was the first to validate various predictive scoring scales in the Chinese cohort of patients with new-onset epileptic seizures or epilepsy of unknown etiology related to neuronal surface Ab-mediated AE. Based upon clinical suspicion, more than one scoring scale should be performed to predict the chance of AE in those patients.

Autoimmune processes in neurological patients are much more common than presently suspected

Autoimmune encephalitides are seldom diseases. How rare they actually are, however, is not known. The low incidence combined with the problematic identification may dampen efforts of neurologists, to identify patients with unclear symptoms as suffering from autoimmune encephalitis. Here, we aim to obtain a better estimate, how many patients with autoimmune disorders should be expected among 100 inpatients in a conventional neurological department. From a total number of 2603 non-stroke patients attended in a 2-year period (2018–2019) 460 CSFs were obtained. From this collection 187 samples (40.7%, > 500 sections) could be analyzed with our immunocytochemical technique. Autoreactive antibodies were detected in 102 (55%) of these 187 CSF samples. Certainly, the presence of autoreactive antibodies does not necessarily indicate that the patient suffers from an autoimmune disease. Our data indicate that from roughly 2000 patients during 1 year about 125 patients with autoreactive CSF antibodies should be expected in a conventional neurological department. This represents the about 35-fold value of what is generally expected at present. Being aware of this high incidence may intensify the efforts of neurologist to identify patients with any type of autoimmune encephalitis. This will be beneficial for patients, because they often profit from immunomodulatory therapy. Interestingly, some CFSs from our patients react with the CA2 subdivision of the hippocampus. While long neglected, recent research places this area into an important position to influence hippocampal network physiology. Autoreactive antibodies in the CSF may disturb the function of CA2 neurons, thereby explaining some neuropsychiatric symptoms in patients with autoimmune encephalitides.

Leucine-rich glioma-inactivated protein 1 antibody-associated encephalitis in a 22-month-old girl: a case report

BackgroundLGI-1 antibody-associated encephalitis is a type of autoimmune encephalitis with a lower prevalence than NMDAR antibody-associated encephalitis. LGI-1 antibody-associated encephalitis is the second most prevalent of all autoimmune encephalitides. LGI-1 antibodies interfere with the interactions of inter-synaptic proteins to produce clinical manifestations (N Engl J Med 378:840–851, 2018).Case presentationLeucine-rich glioma-inactivated protein 1 (LGI-1) antibody-associated encephalitis is a subtype of autoimmune encephalitis with a low incidence. We report a case of a girl aged 22 months with convulsive seizures, psycho-behavioral abnormalities, sleep disorders, and limb tremors. This patient was diagnosed with LGI-1 antibody-associated encephalitis based on electroencephalography (EEG) examinations and autoimmune encephalitis antibody analyses. A combined therapy of anti-epileptic and immunosuppressant drugs was effective in controlling the patient’s neurological symptoms.ConclusionsThe incidence of LGI-1 antibody-associated encephalitis is low and it occurs mostly in middle-aged and elderly patients, although it occasionally occurs in pediatric patients. To the best of our knowledge, this report describes the youngest patient with LGI-1 antibody-associated encephalitis. Following timely diagnosis, administration of anti-epileptic and immunosuppressant therapy was remarkably effective.

Main Syndrome and Antibody Effects of Autoimmune Encephalitis Caused by Antineuronal Surface Antibodies: An Update

Since the discovery of a series of antineuronal surface antibodies (NSAs), the diagnostic approach and management of patients with autoimmune encephalitis (AE) and related disorders have undergone a "paradigm shift." However, recent topics described below are also announcing the dawn of the next era in the practice of patients with AE. As the clinical spectrum of NSA-associated AE expands, some types of AE (e.g., anti-DPPX antibody-associated and anti-IgLON5 antibody-associated disorders) can be misclassified into reconsider diagnosis when using the previously published diagnostic criteria. Nobel active immunization animal models of NSA-associated disorders (e.g., anti-NMDAR encephalitis model) can remarkably emphasize the understanding of the pathophysiological effects and main syndrome induced by NSAs. Additionally, several international clinical trials (e.g., rituximab, inebilizumab, ocrelizumab, bortezomib, and rozanolixizumab) for AE treatments, including anti-NMDAR encephalitis, have been implemented. Data from these clinical trials can be used to establish the best treatment of AE.

Quantitative brain 18F-FDG PET/CT analysis in seronegative autoimmune encephalitis (P11-3.005)

<h3>Objective:</h3> To determine if PET/CT is abnormal in less differentiated forms of autoimmune encephalitis (AE), including seronegative AE and steroid-responsive encephalopathy with associated thyroiditis (SREAT), and whether specific patterns of dysmetabolism exist. <h3>Background:</h3> Brain ¹⁸F-FDG PET/CT (PET) has been established as a useful tool in evaluating AE. Specific patterns of dysmetabolism have been identified in patients with anti-N-methyl-D-aspartate (NMDA) and anti-leucine-rich-glioma-inactivated-1 (LGI-1) AE, and preliminary evidence suggests that PET dysmetabolism may correlate with clinical functional status. <h3>Design/Methods:</h3> We conducted a retrospective cross-sectional analysis of PET scans in people with seronegative AE and SREAT. Utilizing NeuroQ™ software, the Z-scores of 47 brain regions were calculated compared to healthy controls, displayed in heat maps, and visually and statistically compared between study groups and to previous data from NMDA and LGI1 cohorts. <h3>Results:</h3> Sixteen seronegative AE and 4 SREAT patients were identified. All PET scans demonstrated abnormal FDG uptake, while MRI, EEG and CSF were abnormal less frequently in both groups. Both seronegative and SREAT patients demonstrated hypometabolism in the medial frontal, inferior frontal and parieto-temporal regions, and hypermetabolism in the medial temporal lobes. Regions of dysmetabolism were significantly different from NMDA and LGI1 patient data, an effect driven by greater severity of dysmetabolism in the NMDA and LGI1 patients. Follow up scans for 3 seronegative AE patients suggest the degree of dysmetabolism on PET correlates with functional status. <h3>Conclusions:</h3> PET is a useful tool in the evaluation of autoimmune encephalitis. SREAT and seronegative AE represent less differentiated forms of AE. Though frequently abnormal, as anticipated, the pattern of dysmetabolism in SREAT and seronegative AE were less distinct than in NMDA and LGI-1. The pattern of dysmetabolism observed here in SREAT patients was not markedly distinct from seronegative AE patients, potentially supporting consideration of SREAT as a type of seronegative AE rather than a distinct disease entity. <b>Disclosure:</b> Dr. Roman has nothing to disclose. Dr. Sadaghiani has nothing to disclose. Dr. Diaz-Arias has nothing to disclose. Marion Le Marechal has nothing to disclose. Dr. Venkatesan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen Pharmaceuticals. The institution of Dr. Venkatesan has received research support from NIH. The institution of Dr. Venkatesan has received research support from MSRCF. The institution of Dr. Venkatesan has received research support from U.S. DOD. Dr. Probasco 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 NEJM Journal Watch Neurology.

Use of anti-seizure medications in different types of autoimmune encephalitis: A narrative review.

Seizures are the main manifestation of the acute phase of autoimmune encephalitis (AE). Anti-seizure medications (ASMs) play an important role in controlling seizures in AE patients, but there is currently a lack of consensus regarding the selection, application, and discontinuation of ASMs. This narrative review focuses on the use of ASMs in patients with AE driven by different antibodies. The PubMed, Embase, and MEDLINE databases were searched up until 30 October 2022 using prespecified search terms. We identified 2,580 studies; 23 retrospective studies, 2 prospective studies and 9 case reports were evaluated based on our inclusion criteria. Anti-N-methyl-D-aspartic-acid-receptor (anti-NMDAR) encephalitis is the type of AE that responds best to ASMs, and long-term or combined use of ASMs may be not required in most patients with seizures; these results apply to both adults and children. Sodium channel blockers may be the best option for seizures in anti-leucine-rich-glioma-inactivated-1 (anti-LGI1) encephalitis, but patients with anti-LGI1 encephalitis are prone to side effects when using ASMs. Cell surface antibody-mediated AE patients are more likely to use ASMs for a long period than patients with intracellular antibody-mediated AE. Clinicians can score AE patients' clinical characteristics on a scale to identify those who may require long-or short-term use of ASMs in the early stage. This review provides some recommendations for the rational use of ASMs in encephalitis mediated by different antibodies with the aim of controlling seizures and avoiding overtreatment.

Autoimmune encephalitis : Part 1 (Epidemiology, Pathophysiology and Clinical spectrum)

Since the identification of anti-N-methyl-D-aspartate (NMDA) receptor antibodies about 15 years ago, many patients with rapidly progressing psychiatric symptoms, abnormal movements, seizures or unexplained coma, have been diagnosed with autoimmune encephalitis (AE). The symptom onset is often unspecific and might mimic psychiatric disease, but the later course is frequently characterized by severe disease, often requiring intensive care. Clinical and immunological criteria are helpful in identifying the patients, but no biomarkers exist to guide the clinician in therapy or predict outcome. While persons of all ages can be affected by AE, some types of AE affect more children and young adults and are more prevalent in women. This review will focus on encephalitides associated with neuronal cell-surface or synaptic antibodies, which can result in characteristic syndromes, and are often recognizable on clinical grounds. AE subtypes associated with antibodies against extracellular epitopes can occur with or without tumours. Because the antibodies bind and alter the function of the antigen, the effects are often reversible if immunotherapy is initiated, and the prognosis is favourable in most instances. The first part of this series will introduce the topic, provide an overview of current neuronal surface antibodies and how they present, describe the most common subtype, anti-NMDA receptor encephalitis, and discuss the difficulties in recognizing patients with underlying AE amongst patients with new onset psychiatric disorders.

Guest editorial:

Since the identification of anti-N-methyl-D-aspartate (NMDA) receptor antibodies about 15 years ago, many patients with rapidly progressing psychiatric symptoms, abnormal movements, seizures or unexplained coma, have been diagnosed with autoimmune encephalitis (AE). The symptom onset is often unspecific and might mimic psychiatric disease, but the later course is frequently characterized by severe disease, often requiring intensive care. Clinical and immunological criteria are helpful in identifying the patients, but no biomarkers exist to guide the clinician in therapy or predict outcome. While persons of all ages can be affected by AE, some types of AE affect more children and young adults and are more prevalent in women. This review will focus on encephalitides associated with neuronal cell-surface or synaptic antibodies, which can result in characteristic syndromes, and are often recognizable on clinical grounds. AE subtypes associated with antibodies against extracellular epitopes can occur with or without tumours. Because the antibodies bind and alter the function of the antigen, the effects are often reversible if immunotherapy is initiated, and the prognosis is favourable in most instances. The first part of this series will introduce the topic, provide an overview of current neuronal surface antibodies and how they present, describe the most common subtype, anti-NMDA receptor encephalitis, and discuss the difficulties in recognizing patients with underlying AE amongst patients with new onset psychiatric disorders.

Autoimmune encephalitis: an observational study from South India

BackgroundEver since AE was acknowledged as a potentially treatable cause of encephalitis, it has been increasingly recognised worldwide. Data suggests that these disorders are under-recognized, which calls for an increased awareness of the varying clinical, laboratory, electrophysiological and radiological presentations of the different types of autoimmune encephalitis. This cross-sectional observational study included all patients diagnosed with AE, who presented to a tertiary care centre from June 2016 to January 2021. Data were collected including patient’s demography, clinical, laboratory, radiological and electrophysiology studies, management and outcomes.Results31 study participants were included, of which 13 patients were anti-NMDA antibody positive, 12 patients were anti-LGI1 antibody positive, 2 patients were anti-CASPR2 antibody positive, 2 were positive for dual positive status (anti-LGi1 and anti-CASPR2), and one each for anti-GABA-B and anti-GAD 65. There was a marginal male predilection with overall seizures being the most common symptom (68%) followed by behavioural disturbance (64.5%), and impairment of consciousness (32.3%). Patients with Anti-NMDA encephalitis were likely to be young females, with CSF pleocytosis, a more protracted hospital course with more chances of relapse and residual disease, while the patients with anti-Lgi1 encephalitis were likely to be older males with a shorter, less severe hospital course.ConclusionThe present study detailed the demographic, clinical, imaging, laboratory and EEG characteristics of 31 AE patients from a tertiary centre. The findings concurred with the literature and demonstrate the diverse spectrum of clinical manifestations of patients with AE, present with.

Clinical characteristics and short-term outcomes of autoimmune encephalitis in adults

To characterize clinical, paraclinical features and short-term outcomes in different types of autoimmune encephalitis (AE) in a one-center cohort of Russian patients, as well as to evaluate the frequency and significance of the joint expression of antineuronal and anti-glial antibodies (Abs) in AE. Forty-one patients were diagnosed with AE at the Research Center of Neurology from November 2020 to December 2022. Demographic, clinical characteristics, results of laboratory tests, MRI of brain, treatment and outcomes of disease were analyzed. The analysis of Abs to glial antigens (myelin-oligodendrocyte glycoprotein - MOG, glial fibrillar acidic protein - GFAP, aquaporin 4 - AQP-4) was performed by indirect immunofluorescence assay (Euroimmun, Germany). In 24 (58.5%) patients was established definite AE, confirmed by specific Abs detection; in 2 (4.9%) - definite limbic encephalitis, in 15 (36.6%) - seronegative probable AE (including 3 cases of Hashimoto's encephalitis). GFAP-Abs in cerebrospinal fluid (CSF) were detected only in two patients - with clinical and MRI-picture of autoimmune GFAP-astrocytopathy (A-GFAP-A). GFAP- and MOG-Abs in the blood were detected in 25.7% and 6%, respectively, AQP-4-Abs were not detected. There were no correlations between co-expression with glial Abs and clinical characteristics. Systemic and antithyroid Abs were present in 15% and 31%, respectively. Paraneoplastic AE accounted for 22%. For the first time in the Russian population, 2 cases of A-GFAP-A, 6 cases of AE associated with COVID-19 were described. The most common first syndrome were epileptic seizure (34%), psychiatric (29%) and cognitive (14%) disorders. Relapses of AE was observed in 22%. Inflammatory changes in CSF were detected in 41%, focal changes on MRI in 68%. First-line immune therapy was performed in all patients, 85% of cases received pulse therapy with methylprednisolone. Second-line immune therapy (rituximab or cyclophosphamide intravenously) was performed in 19.5%, 78% of patients achieved significant improvement during treatment (scores ≤2 on the modified Rankin scale). The results allow us to consider COVID-19 as a trigger of AE. The absence of detection of GFAP-Abs in CSF in patients with other types of AE contributes to the confirmation of the specificity of GFAP-seropositivity of CSF for the diagnosis of A-GFAP-A. The expression of GFAP- and MOG-Abs in AE can serve as confirmation of the immuno-mediated etiology of the disease, which is especially important for the AE diagnosis in the absence of antineuronal Abs.

Author Response: Neurofilament Light Chain Levels in Anti-NMDAR Encephalitis and Primary Psychiatric Psychosis.

We appreciate the comments of Dr. Vale on our study,1 reminding us that psychosis is a severe ailment and that patients may benefit from CSF studies. As shown by most of our work, we agree that CSF studies should be reincorporated in the evaluation of patients with new onset psychosis.1,2 Dr. Vale also indicates that there are other types of autoimmune encephalitis (AE), and the detection of NMDA receptors (NMDAR) antibodies is not essential for AE diagnosis. We are aware of this concept.3 As indicated in our manuscript, most cases of AE can associate with symptoms of psychosis, but the presence of concurrent neurologic alterations readily excludes a primary psychiatric etiology on clinical grounds. By contrast, the initial symptoms of anti-NMDAR encephalitis can mimic to perfection a first episode of psychosis due to a primary psychiatric disorder.2,4 For this reason, we narrowed our study to this specific AE. Regardless of whether neurofilament light chain (NfL) levels can be found to be elevated in many disorders with neuronal/axonal damage, determination of NfL showed clinical utility in the context of our study.

Clinical validation of the 2020 diagnostic approach for pediatric autoimmune encephalitis in a single center

Objective: To evaluate the value of the 2020 diagnostic criteria (Cellucci criteria) for pediatric autoimmune encephalitis (AE) in children with suspected AE in a single center. Methods: The clinical data of 121 children hospitalized at the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2021, with a diagnosis of suspected AE, were retrospectively collected and analyzed. The children were divided into definite antibody-positive AE (dAPAE), probable antibody-negative AE (prANAE), possible AE (pAE) and non-AE groups according to the Chinese expert consensus and the Graus criteria. A new diagnosis was made according to the Cellucci criteria which was compared with the clinical diagnosis to evaluate the diagnostic value of the Cellucci criteria. The Mann-Whitney U test, Kruskal-Wallis test, and χ2 test were used to compare the differences among groups. The sensitivity and specificity were used to evaluate efficacy of the Cellucci criteria. Results: Among the 121 children, 72 were males and 49 were females, with an age of 10.3 (6.5, 14.0) years at disease onset. There were 99 cases diagnosed as AE according the clinical diagnosis (58 males and 41 females), of which 43 cases were diagnosed as dAPAE, 14 cases as prANAE and 42 cases as pAE, and the other 22 cases were not AE (14 males and 8 females). The top 2 initial symptoms in the 99 children with AE were seizures (53 cases, 53.5%) and abnormal mental behaviors (35 cases, 35.4%). And the most common symptoms during the course of the disease were abnormal mental behaviors (77 cases, 77.8%) and seizures (64 cases, 64.6%). There were statistically differences in the incidence of consciousness disorders, autonomic dysfunctions during the course of the disease and the length of hospitalization among the 4 groups (χ2=21.63, 13.74, H=22.60, all P<0.05). Ninety-six of the 121 children were tested for AE-related antibodies, of which 45 cases (46.9%) were antibody-positive. According to the Cellucci criteria, 42 cases were diagnosed as dAPAE, 34 cases as prANAE and 14 cases as pAE. Compared with the clinical diagnosis, the sensitivity of the Cellucci criteria for the diagnosis of the 3 types of AE were 93.02%, 92.86% and 87.88%, and the specificity were 96.23%, 74.39% and 86.36%, respectively. Conclusions: The Cellucci criteria has a high sensitivity and specificity for the diagnosis of pAE and dAPAE in the clinical management of children with suspected AE, while a high sensitivity but low specificity for the diagnosis of prANAE. Therefore, it is recommended to apply the Cellucci criteria selectively in clinical practice according to the actual situation, especially in the diagnosis of prANAE.

Gut microbiome changes in anti-N-methyl-D-aspartate receptor encephalitis patients

BackgroundAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a type of autoimmune encephalitis. The underlying mechanism(s) remain largely unknown. Recent evidence has indicated that the gut microbiome may be involved in neurological immune diseases via the "gut-brain axis". This study aimed to explore the possible relationship between anti-NMDAR encephalitis and the gut microbiome.MethodsFecal specimens were collected from 10 patients with anti-NMDAR encephalitis and 10 healthy volunteers. The microbiome analysis was based on Illumina sequencing of the V3-V4 hypervariable region of the 16S rRNA gene. The alpha, beta, and taxonomic diversity analyses were mainly based on the QIIME2 pipeline.ResultsThere were no statistical differences in epidemiology, medication, and clinical characteristics (except for those related to anti-NMDAR encephalitis) between the two groups. ASV analysis showed that Prevotella was significantly increased, while Bacteroides was reduced in the gut microbiota of the patients, compared with the controls. Alpha diversity results showed a decrease in diversity in the patients compared with the healthy controls, analyzed by the Shannon diversity, Simpson diversity, and Pielou_E uniformity based on the Kruskal–Wallis test (P = 0.0342, 0.0040, and 0.0002, respectively). Beta diversity analysis showed that the abundance and composition of the gut microbiota was significantly different between the two groups, analyzed by weighted and unweighted UniFrac distance (P = 0.005 and 0.001, respectively).ConclusionsThe abundance and evenness of bacterial distribution were significantly lower and jeopardized in patients with anti-NMDAR encephalitis than in healthy controls. Thus, our findings suggest that gut microbiome composition changes might be associated with the anti-NMDAR encephalitis. It could be a causal agent, or a consequence.

Anti-N-methyl-D-aspartate receptor encephalitis: characteristics and rapid diagnostic approach in the emergency department

BackgroundAnti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a common type of autoimmune encephalitis. Patients with this condition are frequently very ill but are often misdiagnosed in the Emergency Department (ED). The objective of this study was to analyze the clinical characteristics of anti-NMDAR patients in the ED and to identify any associations with a diagnosis of anti-NMDAR encephalitis.MethodsWe performed a retrospective analysis of a prospectively obtained cohort of ED patients from May 2011 to December 2017. We identified patients diagnosed with anti-NMDAR encephalitis in this cohort and extracted key patient characteristics and clinical data, including patient gender, age, presentation, modified Rank Score (m-RS), laboratory test results, significant treatments, and mortality.ResultsEighty-seven patients with anti-NMDAR encephalitis were identified. 54 (62.1%) were female, 23 (26.4%) were < 18 years old, 14 (16.1%) had teratoma, and 45 (51.7%) had an m-RS ≥ 4. Fever, altered mental status, and seizures were the most common symptoms, with a > 50% incidence of each symptom in the cohort. The sensitivity of CSF oligoclonal band (OB) testing was 78.9%. 22 (25.3%) were admitted to the ICU, 20 (23.0%) patients were intubated, but only one patient died (1.1%). 47 (54.0%) were misdiagnosed prior to ED arrival. All patients underwent immunotherapy as first-line treatment for anti-NMDAR encephalitis.ConclusionsA majority of anti-NMDAR encephalitis patients presenting to the ED were female and were likely to be misdiagnosed prior to arrival. Patients with symptoms of fever, altered mental status, and seizures need a lumbar puncture, including CSF OB testing, for definitive diagnosis.

Long-term seizure outcomes in patients with autoimmune encephalitis: A prospective observational registry study update.

This study was undertaken to update and evaluate long-term seizure outcomes in patients with autoimmune encephalitis (AE) based on a large cohort study with long follow-up. In this prospective observational registry study, we analyzed data from patients with AE mediated by common types of neuronal surface antibodies (anti-N-methyl-d-aspartate receptor [NMDAR], anti-leucine-rich glioma-inactivated 1 [LGI1]/contactin-associated protein-like 2 [Caspr2], anti-γ-aminobutyric acid type B receptor [GABAB R]). All patients were recruited from the Department of Neurology at West China Hospital between October 2011 and June 2019, and data were collected prospectively on their demographic and clinical characteristics, treatment strategy, and seizure outcomes, with a median follow-up of 42months (range = 6-93months). Potential risk factors associated with seizure recurrence were also assessed. Of 320 AE patients, 75.9% had acute seizures, among whom >90% of patients had their last seizure within 12months of disease onset. During our follow-up, 21 (9.3%) patients experienced seizure recurrence. Patients with anti-GABAB R encephalitis had a higher cumulative incidence of seizure recurrence than those with anti-NMDAR (log-rank p=.03) or anti-LGI1/Caspr2 encephalitis (log-rank p=.04). Among patients with anti-NMDAR encephalitis, women had a significantly higher cumulative incidence of seizure recurrence than men (log-rank p=.01). Interictal epileptiform discharges (IEDs) or seizures captured on continuous electroencephalogram (EEG) in the acute phase were identified as potential risk factors for seizure recurrence (p=.04, p=.007). Among 163 patients with ≥24months of follow-up, five (3.1%) showed persistent seizures and required ongoing antiseizure medications despite aggressive immunotherapy. Seizure recurrence occurred in a small number of patients and chronic epilepsy occurred in 3.1% of patients during prolonged follow-up. Across all types of AE, risk factors for seizure recurrence were IEDs or seizures captured on EEG in the acute phase; for anti-NMDAR encephalitis, female sex was also a risk factor.

Novel qEEG Biomarker to Distinguish Anti-NMDAR Encephalitis From Other Types of Autoimmune Encephalitis.

ObjectiveTo establish the diagnostic biomarker of electroencephalogram (EEG) to distinguish between anti-N-methyl-d-aspartate receptor encephalitis (NMDARE) and other types of autoimmune encephalitis (other AEs).MethodsWe reviewed the clinical records of 90 patients with acute encephalitis who were treated in our institution between January 2014 and October 2020. We enrolled the patients who fulfilled the diagnostic criteria for possible AE (pAE) defined by Graus et al. (pAE criteria) and then classified into definite NMDARE and other AEs. We investigated the main syndrome and analyzed all admission EEGs using EEG power value (PV). Statistical significance was tested using the Mann–Whitney U test or Fisher’s exact test.ResultsTwenty-five patients fulfilled the pAE criteria and were classified into 9 with definite NMDARE (median age: 21 years; 8 women) and 12 with other AEs (median age: 37.5 years; 6 women). Four were eventually excluded. Speech dysfunction (9/9 vs. 4/12, p = 0.005) and movement disorders (6/9 vs. 1/12, p = 0.016) were more frequent in NMDARE than in other AEs. The PV analyses revealed the novel quantitative EEG (qEEG) index, namely, fast slow ratio (FSR) (PV of total beta/PV of total theta + delta). The median FSR (0.139 vs. 0.029, p = 0.004) was higher for NMDARE than other AEs, and the receiver operating characteristic curve area of FSR was 0.86 (95% CI 0.70–1.00). A cutoff value of 0.047 yielded a specificity of 0.75 and a sensitivity of 1.00. Focusing on patients who did not meet the “probable NMDARE criteria” in Graus 2016 (proNMDARE criteria) (n = 10), the pretest probability of NMDAR antibody test was 0.30 (3/10), which increased in patients with an FSR greater than the cutoff (n = 5) to 0.60 (3/5).ConclusionsThe NMDARE group highlighted speech dysfunction and movement disorders, and a novel qEEG index FSR accurately distinguished the NMDARE patients from other AEs. The FSR is a promising diagnostic marker for NMDARE that indicates the positive results of NMDAR antibodies in patients with AE when combined with the proNMDARE criteria.

Research progress of anti-γ-aminobutyric acid B receptor encephalitis and a case report of paraneoplastic associated encephalitis and treatment analysis.

Encephalitis is one of the common diseases in neurology. Early diagnosis and appropriate treatments are essential. Autoimmune encephalitis (AE) generally refers to a type of encephalitis mediated by autoimmune mechanisms. It is gradually considered to be an important cause of reversible encephalitis caused by noninfectious factors. It can occur in children, adolescents, and adults, and is clinically characterized by multifocal or diffuse brain damage such as personality changes, seizures, and cognitive impairment, with an overall good effect of immunotherapy. According to the clinical features of the patients, blood and cerebrospinal fluid tests, neuroelectrophysiology, cranial imaging, treatment and prognosis, AEs can be broadly divided into specific antigen (antibody)-related AEs and nonspecific antigen (or antibody) -related AEs. With the development of AEs research, more and more anti-neuron antibodies have been found, which provides an important reference for the diagnosis and treatment of AEs. Understanding the knowledge about AEs is important to discover new diseases and deepen the understanding of the immunopathological mechanisms of existing central nervous system diseases. Anti-γ-aminobutyric acid B (GABA-B) receptor encephalitis is a type of AE, but this disease is rare in AE, often develop to the clinical manifestations of marginal encephalitis, accompanied by obvious seizures or status epilepticus, Some patients had tumors, mainly small-cell carcinoma, prompt diagnosis, early immunotherapy and, if necessary, tumor treatment resulted in complete or partial neurological improvement in most patients.