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Objectiveto assess the performance of the Anti-N-Methyl-D-Aspartate Receptor encephalitis (NMDAR) One-Year Functional Status (NEOS) score in predicting one-year functional outcome in Chinese children with anti-NMDAR encephalitis.Methodschildren with anti-NMDAR encephalitis at the Children’s Hospital of Chongqing Medical University were retrospectively enrolled from January 2014 to December 2020. Patients were categorized into two groups based on the modified Rankin Scale (mRS) at one-year follow-up. Discrimination of the NEOS score was assessed by the area under curve (AUC) of the receiver operating characteristic curve. Calibration of the NEOS score was assessed by comparing predicted probabilities with observed probabilities using a calibration curve and the Hosmer-Lemeshow test. The clinical practicability of the NEOS score was evaluated by performing a decision curve analysis.Resultsone hundred seventy-five children (101 females and 74 males) with anti-NMDAR encephalitis and a median age of 7.7 years were enrolled. Of those, 149 (85.1%) had a good outcome at 1 year (mRS ≤ 2), and the remaining 26 (14.9%) had a poor outcome (mRS > 2). Patients with a higher NEOS score had a significantly higher mRS at one-year follow-up [Spearman r = 0.3878, 95% confidence interval (CI): 0.2500-0.5103, P < 0.001]. The AUC of the NEOS score was 0.870 (95% CI: 0.801-0.938, P < 0.001). The observed probability and predicted probability showed moderate consistency in the calibration curve and the Hosmer-Lemeshow test (P = 0.912). The decision curve analysis showed that using the NEOS score to predict one-year outcomes could provide additional net benefit during clinical practice.Conclusionsthe NEOS score is a potentially reliable model to predict the one-year functional outcome in Chinese children with anti-NMDAR encephalitis.

ObjectiveTo investigate the relapse rate and study the factors that may predict the subsequent relapse in anti-NMDAR, anti-GABABR and anti-LGI1 encephalitis in Northeast China.MethodsIn the retrospective cohort study, we consecutively enrolled patients with anti-N1MDAR, anti-GABABR and anti-LGI1 encephalitis between March 2015 and November 2021. The patients were followed up for at least 6 months. The outcome variable was a binary variable of relapse or not. Predictors of relapse were identified.ResultsA total of 100 patients were enrolled. Relapse occurred in 26 (26%) patients after a median follow-up of 18 months since the first event. The relapse rates of anti - NMDAR, anti - GABABR and anti - LGI1 encephalitis were 25%, 33.3%, and 28.6%, respectively. The multivariable analysis results suggested that immunotherapy delay at the acute phase was independently associated with an increased risk of relapse in total patients (HR = 2.447, 95% CI = 1.027 - 5.832; P = 0.043). Subgroup analysis results showed that antibody titer was associated with the likelihood of relapse in anti-LGI1 encephalitis. The higher the concentration, the more likely it was for patients to have relapse (p=0.019).ConclusionThe general relapse rate of anti-NMDAR, anti-GABABR and anti-LGI1 encephalitis was 26%. The risk of subsequent relapse was elevated in those with delayed immunotherapy in the first episode. In subgroup of anti-LGI1 encephalitis, higher antibody titer was the risk factors of relapse. Thus, timely and aggressive immunotherapy may be beneficial for patients to prevent subsequent relapse.

Herein, we reported a case of a young man diagnosed with MNOS (anti-myelin oligodendrocyte glycoprotein associated disease (MOGAD) and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis overlapping syndrome, i.e., MNOS), whose imaging findings in magnetic resonance imaging (MRI) mimicked chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). We reported a case of refractory anti-NMDAR encephalitis that recurred after standard first-line and second-line treatment. The patient presented with CLIPPERS on imaging at recent hospital admission, and his MOG antibodies were seropositive. After intravenous methylprednisolone (IVMP) treatment, the patient’s symptoms were significantly alleviated. In this case, we demonstrated that MNOS could mimic the radiological characteristics of CLIPPERS. Future studies should focus on the diagnosis and treatment of antibody overlap syndrome.

ObjectivesThis study reported a case of overlapping anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and myelin oligodendrocyte glycoprotein (MOG) inflammatory demyelinating disease with human herpesviruses 7 (HHV-7) infection.MethodsThe detailed clinical characteristics, neuroimaging features, and outcomes of the patient were collected. Polymerase chain reaction (PCR), cell-based assay (CBA) and the tissue-based indirect immunofluorescence assay (TBA) were used for diagnosis.ResultsThe clinical manifestations included headache, dizziness, fever, optic neuritis, and epileptic-seizures. Brain magnetic resonance imaging (MRI) showed hyperintensities involving the left frontal, orbital gyrus and bilateral optic nerve with substantial contrast enhancement. Moreover, test for HHV-7 DNA by using the next generation sequencing metagenomics and polymerase chain reaction showed positive result in CSF but not in the serum samples. Anti-HHV-7 IgM and IgG antibodies were detected in both the serum and cerebrospinal fluid. NMDAR antibodies (1:10) were found positive in the patient’s CSF by a cell-based assay, and MOG antibodies were positive in the serum (1:10) and CSF (1:32). The patient appeared to respond well to immune therapy and it was found that the clinical symptoms including epileptic-seizure as well as headache were relieved and cerebral lesions almost disappeared after the treatment. However, his vision was not completely restored even at the 8-month follow-up, especially the vision in his right eye which was more seriously damaged.DiscussionWe report a rare case of MOG antibodies and anti-NMDAR encephalitis overlapping syndrome (MNOS) with HHV-7 infection for the first time. The possibility of MNOS needs be considered when optic neuritis occurs in the patients diagnosed with anti-NMDAR encephalitis. Besides, immunotherapy should be initiated as early as possible to improve the treatment outcomes and facilitate complete cure.

ObjectiveThis study aimed to evaluate the clinical characteristics and long-term surgical outcomes of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis with teratoma.MethodsPatients who were admitted to West China Hospital from June 2012 to June 2019 and diagnosed with anti-NMDAR encephalitis were enrolled in the study. Medical records were reviewed prospectively to gather clinical characteristic data. Patients were followed up at long-term every 3 months.ResultsThis study included 192 patients, among whom 21 (10.9%) were detected with having a teratoma. Patients included 20 women, with a mean age of 24.62 ± 7.61 years. Seizure and psychiatric symptoms were the most dominant symptoms in both groups, followed by memory deficits. Central hypoventilation (52.4 vs. 17%, p < 0.001) and decreased consciousness (71.4 vs. 31.3%, p = 0.002) were significantly more frequent in patients with teratoma than in those without. Moreover, the anti-NMDAR antibody titer was higher (p = 0.021) and the baseline modified Rankin scale score was lower (p = 0.004) in patients with teratoma than in those without. First-line immunotherapy was performed in 21 (100%) patients with teratoma and 167 (97.7%) patients without teratoma. All patients with teratoma had the tumor removed. During follow-up, two (9.5%) patients with teratoma and 11 (6.4%) patients without teratoma died, whereas 1 (4.8%) patient with teratoma and 37 (21.6%) patients without teratoma had relapses. Overall, 19 (90.5%) patients with teratoma and 151 (88.3%) patients without teratoma achieved favorable clinical outcomes at the final follow-up.ConclusionsWith early detection and removal of teratoma, most patients with anti-NMDAR encephalitis and teratoma achieved a favorable long-term prognosis.

ObjectivesThe purpose of this study was to investigate the association of neutrophil percentage-to-albumin ratio (NPAR) with the severity at admission and discharge (short-term prognosis) in patients with anti-N-methyl-D-aspartic acid receptor (NMDAR) encephalitis.MethodsMultivariable logistic regression models such as NPAR were constructed based on univariable regression results. Receiver operating characteristic (ROC) curves, nomograms, and concordance index (c-index) were used to evaluate the efficacy of the models in assessing disease severity at admission and predicting short-term prognosis, validated by bootstrap, Hosmer–Lemeshow goodness-of-fit test, calibration curves, and decision curve analysis.ResultsA total of 181 patients with anti-NMDAR encephalitis diagnosed at the First Affiliated Hospital of Zhengzhou University were included. The results showed that NPAR had good sensitivity and specificity in assessing disease severity at admission and predicting short-term prognosis. The multivariable logistic regression models based on NPAR and other influencing factors had good discrimination, consistency, accuracy, calibration ability, applicability, and validity in assessing the severity at admission and predicting short-term prognosis.ConclusionNPAR has good clinical value in assessing disease severity at admission and predicting short-term prognosis of patients with anti-NMDAR encephalitis.

The most common type of autoimmune encephalitis is anti-NMDAR-encephalitis. It is characterized by IgG antibodies against the GluN1 subunit of the NMDA receptor, leading to marked neuropsychiatric and behavioural symptoms that progress in a subacute manner to seizures, speech abnormalities, and a depressed level of consciousness. In this case report, the clinical course of a 30-year-old man who first received treatment for viral encephalitis after exhibiting normal symptoms is described. CSF showed lymphocytic pleocytosis with normal brain imaging. The EEG demonstrated diffuse slowing and encephalopathy. An autoimmunity encephalitis workup was done after exhaustive investigations for metabolic and infectious causes came back negative. A diagnosis of anti-NMDAR encephalitis was made after antibodies were found in the CSF. [ABSTRACT FROM AUTHOR]

Purpose: The reported prevalence of abnormal findings by brain MRI varies from 11 to 83% among patients with anti- N -methyl-D-aspartate receptor (NMDAR) encephalitis. Here, we investigated the prevalence of abnormal MRI findings in Chinese patients and explored whether such findings are correlated with clinical outcomes. Methods: This retrospective study analyzed a consecutive series of 52 patients with anti-NMDAR encephalitis admitted to our hospital. The patients were assigned to the "MRI-normal" or the "MRI-abnormal" group based on brain MRI after admission. The groups were compared in terms of clinicodemographic characteristics and scores on the Mini-Mental State Examination (MMSE) and modified Rankin Scale (mRS) 3 and 12 months after admission. Results: Thirty-seven (71.15%) of the patients showed abnormalities on brain MRI; these patients were more likely to be men and showed abnormalities on electroencephalography. Patients who showed normal or abnormal MRI findings did not differ significantly in terms of clinical symptoms, rates of mortality or relapse, or mRS scores after 3 and 12 months. However, patients with abnormal MRI showed significantly lower MMSE scores than those with normal MRI after 3 and 12 months. Conclusions: We found high prevalence of abnormal MRI findings in our sample of Chinese patients with anti-NMDAR encephalitis. We also found that the abnormal findings were associated with cognitive decline but not necessarily with mortality or functional outcomes in the short or long term. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the mortality rate and identify the predictors of death in patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis. Methods: Patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis were recruited from the Neurology Department of the First Hospital of Jilin University from March 2015 to November 2021. The primary outcome variable was a binary variable of death vs. survival. The potential risk factors for mortality were evaluated. The mortality rates were determined, and the independent predictors of death were identified using multivariable logistic regression analysis. Results: A total of 100 hospitalized patients with anti-NMDAR, anti-LGI1, or anti-GABABR encephalitis were included in the final analysis. Fifteen patients (15%) died during a median follow-up period of 18 months. The mortality rates were 10% for anti-NMDAR encephalitis, 2.8% for anti-LGI1 encephalitis, and 41.7% for anti-GABABR encephalitis. The multivariable analysis results showed that older age at onset [adjusted odds ratio (OR) = 1.017, 95% confidence interval (CI) = 1.009–1.136; p = 0.023] was independently associated with an increased risk of death. Antibody type was also associated with mortality. Patients with anti-GABABR encephalitis had 13.458-fold greater odds of dying than patients with anti-LGI1 encephalitis (adjusted OR = 13.458, 95% CI = 1.270–142.631; p = 0.031). Conclusion: The general mortality rate of anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis was 15%. Age at onset and type of autoimmune encephalitis antibody were independent predictors of death in these patients. [ABSTRACT FROM AUTHOR]

Background: Anti- N -methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common type of autoimmune encephalitis. Early recognition and treatment, especially distinguishing from viral encephalitis (VE) in the early stages, are crucial for the outcomes of patients with anti-NMDAR encephalitis. Compared with plasma microRNAs (miRNAs), exosomal miRNAs are more abundant and not easy to degrade. Moreover, exosomes can pass through the blood–brain barrier. This study aimed to explore the clinical value of serum exosomal miRNAs in the differential diagnosis of anti-NMDAR encephalitis with VE. Method: Serum samples from a total of 30 patients with anti-NMDAR encephalitis, 30 patients with VE, and 30 cases of control patients hospitalized in the same period were collected. Firstly, the serum exosomes were isolated and identified by transmission electron microscope (TEM), nanoparticle-tracking analyzer (NTA), and Western blot (WB). The expression levels of let-7b and miR-140-5p from serum exosomes were detected by real-time quantitative PCR (qPCR). At the same time, we also detected complement 3 (C3), complement 4 (C4), and high sensitivity CRP (hs-CRP) expression levels in three groups. Finally, we analyzed the difference and diagnostic value of the test results. Results: Isolated particles showed identical characteristics to the exosomes through TEM, NTA, and WB analyses. Compared with the VE group and control group, the expression of miR-140-5p was significantly upregulated in serum exosomes of the NMDAR group. In contrast, the serum C3 in the NMDAR group was significantly lower than the other two groups. ROC curve analysis showed the area under the curve (AUC) of serum exosomal miR-140-5p and serum C3 was 0.748 (76.67% sensitivity and 73.33% specificity) and 0.724 (76.67% sensitivity and 60% specificity) to distinguish anti-NMDAR encephalitis from VE, respectively. The AUC of serum exosomal miR-140-5p combined with serum C3 was 0.811, the sensitivity was 70.00%, and the specificity was 86.67%. Conclusion: Serum exosomal miR-140-5p combined with serum C3 would be a promising marker in the differential diagnosis of anti-NMDAR encephalitis with VE. [ABSTRACT FROM AUTHOR]

Autoimmune encephalitis is characterized by mental and behavioral symptoms, seizures, and cognitive impairment. The presence of schizophrenia needs to be distinguished from that of autoimmune encephalitis. Herein, we describe the case of a woman who exhibited abnormal mental behavior and cognitive impairment. The patient had experienced similar symptoms more than 20 years previously and had been diagnosed with schizophrenia. The patient's psychotic symptoms improved after treatment with antipsychotic drugs; however, cognitive impairment persisted. She was diagnosed with anti-N-methyl-D-aspartate (NMDA)-receptor concurrent with anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor encephalitis. She showed improvement after treatment with steroids and intravenous immunoglobulins (IVIgs). Furthermore, we reviewed the literature and found that, including the present case, 10 patients have been diagnosed with anti-NMDA concurrent with anti-AMPA-receptor encephalitis. Three of these patients were men and seven were women, and their ages ranged from 21 to 71 years. Moreover, seven (70%) patients had a history of tumors. Symptoms of these patients included psychotic symptoms, varying degrees of consciousness disturbance, seizures, dyskinesia, dystonia, autonomic dysfunction, agitation, and verbal reduction. Brain magnetic resonance imaging findings showed scattered fluid-attenuated inversion recovery hyperintensity in subcortical white matter and/or medial temporal lobe in seven (70%) patients. After combination treatment, including tumor removal and administration of steroids, IVIg, plasma exchange, or immunity inhibitors, the symptoms improved in part of the patients. It is necessary to exclude autoimmune encephalitis for patients with psychiatric manifestations and cognitive impairment. Timely combination therapy is important in anti-NMDA-receptor concurrent with anti-AMPA-receptor encephalitis. [ABSTRACT FROM AUTHOR]

Rationale: Adequate immunotherapies for anti-NMDAR encephalitis during pregnancy produce a relatively good clinical outcome for pregnant mothers and their infants, but there are no reports about the future growth of their babies. The damage of anti-NMDAR antibodies to early neuronal development is still unknown. Objectives: Serum or cerebrospinal fluid from one patient with anti-NMDAR encephalitis (the index patient) and one patient with schizophrenia (the control patient) was administered to primary cultures of dissociated rat cortical neurons, and dendritic outgrowth, centrosome elimination, and branching of dendrites were investigated. For rescue experiments, serum of the index patient was replaced with normal culture media after 3 days' administration of the index patient. Results: Serum and cerebrospinal fluid of the index patient statistically significantly impaired dendritic outgrowth of cultured rat cortical primary neurons. Serum of the index patient also statistically significantly delayed centrosome elimination. Impaired dendritic outgrowth and delayed centrosome elimination were not perfectly rescued by changing to normal culture media. Serum of the index patient also statistically significantly reduced the branching of dendrites. Conclusions: This is the first demonstration of the damage by anti-NMDAR antibodies on early dendritic development in vitro. As a strategy to protect embryonic neurons, our findings may support the efficacy of early immunotherapy for anti-NMDAR encephalitis in pregnancy. [ABSTRACT FROM AUTHOR]

Background: Triphasic waves (TWs) are mainly described in association with metabolic encephalopathy, especially hepatic encephalopathy. Now, as different conditions including non-metabolic and structural abnormalities have been reported to be associated with TWs, the presence of TWs becomes a non-specific finding for metabolic encephalopathy. Case Presentation: We report the first case of anti-NMDAR encephalitis in a 9-year-old girl presenting with TWs on EEG. The TWs background EEG lasted for about 12 h on the 40th day of the disease course. No epileptic wave was found during a series of EEG examinations. The child was discharged from the hospital and no neurological sequelae remained after a six-month follow-up. Conclusions: TWs are not specific to metabolic encephalopathy, but can also occur in children with autoimmune encephalitis. This case achieved a good prognosis after the early initiation of immunotherapy. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical features of common autoimmune encephalitis and evaluate the sensitivity of antibodies contributing to focal epilepsy signs and symptoms (ACES) score. Methods: Collecting and analyzing the data of 242 patients with autoimmune encephalitis (AE) diagnosed in the First Affiliated Hospital of Zhengzhou University from August 2015 to December 2020 in this retrospective study. The six items of the ACES score (cognitive symptoms, behavioral changes, autonomic symptoms, speech problems, autoimmune diseases, temporal MRI hyperintensities) were screened in patients with complete clinical data. Results: (1) In total, 242 patients were included, with 147 cases of anti-N-methyl-D-aspartate receptor encephalitis, 47 cases of anti-γ-aminobutyric acid type B (GABA-B) receptor encephalitis, and 48 cases of anti-leucine-rich glioma inactivating protein 1 (LGI1) encephalitis. The most common clinical symptoms are cognitive impairment (77%), behavioral changes (79%), and seizures (71%). In total, 129 cases (54%) combined with autonomic dysfunction, such as gastrointestinal dysmotility, sinus tachycardia, and central hypoventilation. Twelve patients had autoimmune diseases, most of which were of thyroid diseases. (2) One hundred and twenty-seven patients with complete clinical data evaluated ACES score, 126 cases of whom (126/127, 99.2%) were equal to or >2 points, 1 case (1/127, 0.8%) was of <2 points. Interpretation: (1) Cognitive impairment, abnormal behavior, and seizures are the most common manifestations of AE and autonomic symptoms. Thyroid disease is the most autoimmune disease in AE. Clinically, for patients of suspected AE, increasing the knowledge and testing of thyroid function and rheumatism is necessary. (2) ACES score is a simple, effective, and easy-to-operate score, with a certain screening value for most patients suspected of AE. [ABSTRACT FROM AUTHOR]

Epilepsy is one of the most common neurological disorders characterized by recurrent seizures. The mechanism of epilepsy remains unclear and previous studies suggest that N-methyl-D-aspartate receptors (NMDARs) play an important role in abnormal discharges, nerve conduction, neuron injury and inflammation, thereby they may participate in epileptogenesis. NMDARs belong to a family of ionotropic glutamate receptors that play essential roles in excitatory neurotransmission and synaptic plasticity in the mammalian CNS. Despite numerous studies focusing on the role of NMDAR in epilepsy, the relationship appeared to be elusive. In this article, we reviewed the regulation of NMDAR and possible mechanisms of NMDAR in epilepsy and in respect of onset, development, and treatment, trying to provide more evidence for future studies. [ABSTRACT FROM AUTHOR]

Background and purpose: Anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis is characterized by a range of cognitive impairments, especially in executive function. Our study aims to identify the abnormal regional homogeneity (ReHo) in anti‐NMDAR encephalitis patients and its relationship with the executive function. Methods: Forty patients and 42 healthy volunteers undertook an Attention Network Test and a resting‐state functional magnetic resonance imaging scan. ReHo analysis was performed to investigate the neuronal activity synchronization in all subjects. Based on ReHo analysis, a multivariate pattern analysis (MVPA) was carried out to identify the brain regions that differed the most between the two groups. Results: Compared to controls, the patients had higher executive control scores (p < 0.05). The patients presented reduced ReHo values in the bilateral posterior cerebellar lobe, anterior cerebellar lobe, midbrain, bilateral caudate nucleus, right superior frontal gyrus, right middle temporal gyrus, bilateral inferior parietal lobule and the left middle frontal gyrus. The ReHo values of the bilateral inferior parietal lobule in patients were found to be negatively associated with executive control scores. The classification of patients and controls using MVPA had an accuracy of 76.83%, a sensitivity of 82.50%, a specificity of 71.43% and the area under the curve was 0.83. Conclusions: Our study provides evidence of abnormal cerebral function in anti‐NMDAR encephalitis patients, which may contribute to unveiling the neuropathological mechanisms of anti‐NMDAR encephalitis and their influences on executive dysfunction. The MVPA classifier, based on ReHo, is helpful in identifying anti‐NMDAR encephalitis patients from healthy controls. [ABSTRACT FROM AUTHOR]

Encephalitis is a neurological disorder that develops rapidly into a progressive encephalopathy caused by inflammatory processes in the brain. The incidence of encephalitis in developed countries is 5-10 per 100,000 per year. Encephalitis can affect all ages and cause long-term effects on patients, their families, and society. Autoimmune encephalitis, including anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, is increasingly recognized as a cause of encephalitis in children and has a considerable mortality rate of 5-7%.4 Physicians should suspect anti-NMDAR encephalitis in patients with prominent neuropsychiatric symptoms and movement disorder. We report here a case of anti-NMDAR encephalitis and discuss the role of clinical criteria in diagnosing anti-NMDAR encephalitis in children. [ABSTRACT FROM AUTHOR]

Abstract Background In this study, we report a case of a young female who was hospitalized for seizures and diagnosed with anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis. Case presentation The main feature of this patient was bilateral temporal calcifications detected by routine head computed tomography (CT). The co-existence of anti-NMDAR encephalitis and cerebral calcifications has not been reported. We supposed that the patient had an incomplete form of celiac disease (CD), epilepsy and cerebral calcifications syndrome (CEC). The patient's symptoms were alleviated by a series of treatments, and she remained stable during the follow-ups. Conclusions Our findings confirm the rarity co-existing anti-NMDAR encephalitis and cerebral calcifications. In future clinical work, we need to elucidate the relationship between anti-NMDAR encephalitis and cerebral calcifications, and the association between anti-NMDAR encephalitis and other co-existing autoimmune disorders.

Abstract Seizure is one of the main symptoms of anti‐NMDAR encephalitis, but data of ictal electroencephalogram (EEG) patterns remain limited. In this study, we aimed to introduce a unique ictal pattern. This delta brush variant (DBV) was characterized as generalized delta rhythm with fast spike activity riding on it. We retrospectively evaluated the ictal pattern from six patients with anti‐NMDAR encephalitis, and patients were grouped based on the presence of DBV. DBV was found in two patients who were in the florid phase of the disease: (a) A 17‐year‐old girl experienced rhythmical jerking of bilateral limbs. Corresponding EEG patterns showed generalized DBV. Seizure terminated after intravenous injection of midazolam, but oral‐facial dyskinesia reappeared; and (b) a 24‐year‐old man suffered stiffening of the right limbs and oral‐facial dyskinesia. The EEG pattern showed frontal DBV with left prominence. Seizure was controlled, but oral‐facial dyskinesia remained after intravenous injection of midazolam. Compared with patients without DBV, patients in this group were more likely to have prolonged excessive delta brush (100% vs 25%) and hyperpyrexia (39.7℃ vs 38.2℃). Duration in ICU (36 days vs 18 days) and hospital (52 days vs 36 days) was relatively longer in DBV group, and no significant difference was found in terms of the mRS score (1 vs 0.5) and seizure relapse rate (0% vs 25%) during 3‐month follow‐up. DBV is a peculiar pattern in anti‐NMDAR encephalitis. An EEG‐based monitoring should be considered to avoid misleading this ictal EEG pattern to the electromyographic artifact.

ObjectiveWe aimed to investigate the mortality rate and identify the predictors of death in patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis.MethodsPatients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis were recruited from the Neurology Department of the First Hospital of Jilin University from March 2015 to November 2021. The primary outcome variable was a binary variable of death vs. survival. The potential risk factors for mortality were evaluated. The mortality rates were determined, and the independent predictors of death were identified using multivariable logistic regression analysis.ResultsA total of 100 hospitalized patients with anti-NMDAR, anti-LGI1, or anti-GABABR encephalitis were included in the final analysis. Fifteen patients (15%) died during a median follow-up period of 18 months. The mortality rates were 10% for anti-NMDAR encephalitis, 2.8% for anti-LGI1 encephalitis, and 41.7% for anti-GABABR encephalitis. The multivariable analysis results showed that older age at onset [adjusted odds ratio (OR) = 1.017, 95% confidence interval (CI) = 1.009–1.136; p = 0.023] was independently associated with an increased risk of death. Antibody type was also associated with mortality. Patients with anti-GABABR encephalitis had 13.458-fold greater odds of dying than patients with anti-LGI1 encephalitis (adjusted OR = 13.458, 95% CI = 1.270–142.631; p = 0.031).ConclusionThe general mortality rate of anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis was 15%. Age at onset and type of autoimmune encephalitis antibody were independent predictors of death in these patients.

PurposeThe reported prevalence of abnormal findings by brain MRI varies from 11 to 83% among patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Here, we investigated the prevalence of abnormal MRI findings in Chinese patients and explored whether such findings are correlated with clinical outcomes.MethodsThis retrospective study analyzed a consecutive series of 52 patients with anti-NMDAR encephalitis admitted to our hospital. The patients were assigned to the “MRI-normal” or the “MRI-abnormal” group based on brain MRI after admission. The groups were compared in terms of clinicodemographic characteristics and scores on the Mini-Mental State Examination (MMSE) and modified Rankin Scale (mRS) 3 and 12 months after admission.ResultsThirty-seven (71.15%) of the patients showed abnormalities on brain MRI; these patients were more likely to be men and showed abnormalities on electroencephalography. Patients who showed normal or abnormal MRI findings did not differ significantly in terms of clinical symptoms, rates of mortality or relapse, or mRS scores after 3 and 12 months. However, patients with abnormal MRI showed significantly lower MMSE scores than those with normal MRI after 3 and 12 months.ConclusionsWe found high prevalence of abnormal MRI findings in our sample of Chinese patients with anti-NMDAR encephalitis. We also found that the abnormal findings were associated with cognitive decline but not necessarily with mortality or functional outcomes in the short or long term.

Autoimmune encephalitis is characterized by mental and behavioral symptoms, seizures, and cognitive impairment. The presence of schizophrenia needs to be distinguished from that of autoimmune encephalitis. Herein, we describe the case of a woman who exhibited abnormal mental behavior and cognitive impairment. The patient had experienced similar symptoms more than 20 years previously and had been diagnosed with schizophrenia. The patient's psychotic symptoms improved after treatment with antipsychotic drugs; however, cognitive impairment persisted. She was diagnosed with anti-N-methyl-D-aspartate (NMDA)-receptor concurrent with anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor encephalitis. She showed improvement after treatment with steroids and intravenous immunoglobulins (IVIgs). Furthermore, we reviewed the literature and found that, including the present case, 10 patients have been diagnosed with anti-NMDA concurrent with anti-AMPA-receptor encephalitis. Three of these patients were men and seven were women, and their ages ranged from 21 to 71 years. Moreover, seven (70%) patients had a history of tumors. Symptoms of these patients included psychotic symptoms, varying degrees of consciousness disturbance, seizures, dyskinesia, dystonia, autonomic dysfunction, agitation, and verbal reduction. Brain magnetic resonance imaging findings showed scattered fluid-attenuated inversion recovery hyperintensity in subcortical white matter and/or medial temporal lobe in seven (70%) patients. After combination treatment, including tumor removal and administration of steroids, IVIg, plasma exchange, or immunity inhibitors, the symptoms improved in part of the patients. It is necessary to exclude autoimmune encephalitis for patients with psychiatric manifestations and cognitive impairment. Timely combination therapy is important in anti-NMDA-receptor concurrent with anti-AMPA-receptor encephalitis.

BackgroundAnti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common type of autoimmune encephalitis. Early recognition and treatment, especially distinguishing from viral encephalitis (VE) in the early stages, are crucial for the outcomes of patients with anti-NMDAR encephalitis. Compared with plasma microRNAs (miRNAs), exosomal miRNAs are more abundant and not easy to degrade. Moreover, exosomes can pass through the blood–brain barrier. This study aimed to explore the clinical value of serum exosomal miRNAs in the differential diagnosis of anti-NMDAR encephalitis with VE.MethodSerum samples from a total of 30 patients with anti-NMDAR encephalitis, 30 patients with VE, and 30 cases of control patients hospitalized in the same period were collected. Firstly, the serum exosomes were isolated and identified by transmission electron microscope (TEM), nanoparticle-tracking analyzer (NTA), and Western blot (WB). The expression levels of let-7b and miR-140-5p from serum exosomes were detected by real-time quantitative PCR (qPCR). At the same time, we also detected complement 3 (C3), complement 4 (C4), and high sensitivity CRP (hs-CRP) expression levels in three groups. Finally, we analyzed the difference and diagnostic value of the test results.ResultsIsolated particles showed identical characteristics to the exosomes through TEM, NTA, and WB analyses. Compared with the VE group and control group, the expression of miR-140-5p was significantly upregulated in serum exosomes of the NMDAR group. In contrast, the serum C3 in the NMDAR group was significantly lower than the other two groups. ROC curve analysis showed the area under the curve (AUC) of serum exosomal miR-140-5p and serum C3 was 0.748 (76.67% sensitivity and 73.33% specificity) and 0.724 (76.67% sensitivity and 60% specificity) to distinguish anti-NMDAR encephalitis from VE, respectively. The AUC of serum exosomal miR-140-5p combined with serum C3 was 0.811, the sensitivity was 70.00%, and the specificity was 86.67%.ConclusionSerum exosomal miR-140-5p combined with serum C3 would be a promising marker in the differential diagnosis of anti-NMDAR encephalitis with VE.

Epilepsy is one of the most common neurological disorders characterized by recurrent seizures. The mechanism of epilepsy remains unclear and previous studies suggest that N-methyl-D-aspartate receptors (NMDARs) play an important role in abnormal discharges, nerve conduction, neuron injury and inflammation, thereby they may participate in epileptogenesis. NMDARs belong to a family of ionotropic glutamate receptors that play essential roles in excitatory neurotransmission and synaptic plasticity in the mammalian CNS. Despite numerous studies focusing on the role of NMDAR in epilepsy, the relationship appeared to be elusive. In this article, we reviewed the regulation of NMDAR and possible mechanisms of NMDAR in epilepsy and in respect of onset, development, and treatment, trying to provide more evidence for future studies.

Objective: To analyze the clinical features of common autoimmune encephalitis and evaluate the sensitivity of antibodies contributing to focal epilepsy signs and symptoms (ACES) score.Methods: Collecting and analyzing the data of 242 patients with autoimmune encephalitis (AE) diagnosed in the First Affiliated Hospital of Zhengzhou University from August 2015 to December 2020 in this retrospective study. The six items of the ACES score (cognitive symptoms, behavioral changes, autonomic symptoms, speech problems, autoimmune diseases, temporal MRI hyperintensities) were screened in patients with complete clinical data.Results: (1) In total, 242 patients were included, with 147 cases of anti-N-methyl-D-aspartate receptor encephalitis, 47 cases of anti-γ-aminobutyric acid type B (GABA-B) receptor encephalitis, and 48 cases of anti-leucine-rich glioma inactivating protein 1 (LGI1) encephalitis. The most common clinical symptoms are cognitive impairment (77%), behavioral changes (79%), and seizures (71%). In total, 129 cases (54%) combined with autonomic dysfunction, such as gastrointestinal dysmotility, sinus tachycardia, and central hypoventilation. Twelve patients had autoimmune diseases, most of which were of thyroid diseases. (2) One hundred and twenty-seven patients with complete clinical data evaluated ACES score, 126 cases of whom (126/127, 99.2%) were equal to or >2 points, 1 case (1/127, 0.8%) was of

BackgroundTriphasic waves (TWs) are mainly described in association with metabolic encephalopathy, especially hepatic encephalopathy. Now, as different conditions including non-metabolic and structural abnormalities have been reported to be associated with TWs, the presence of TWs becomes a non-specific finding for metabolic encephalopathy.Case PresentationWe report the first case of anti-NMDAR encephalitis in a 9-year-old girl presenting with TWs on EEG. The TWs background EEG lasted for about 12 h on the 40th day of the disease course. No epileptic wave was found during a series of EEG examinations. The child was discharged from the hospital and no neurological sequelae remained after a six-month follow-up.ConclusionsTWs are not specific to metabolic encephalopathy, but can also occur in children with autoimmune encephalitis. This case achieved a good prognosis after the early initiation of immunotherapy.

Dermoid cysts, or mature cystic teratomas, are germ cell neoplasms that can arise on the ovaries. Being of germ cell origin, such cysts can have extensive variance in presentation, including a rare paraneoplastic effect where they produce N-methyl-D-aspartate receptor (NMDAR) antibodies, resulting in anti-NMDAR encephalitis. This can cause various neuropsychiatric symptoms, including confusion, hallucinations, psychosis, disorientation, and a change in cognition. This case study presents the unusual occurrence of a 39-year-old female patient who presented to the emergency department with encephalitis, headaches, and auditory hallucinations after recent glucocorticoid use. Through an extensive workup, imaging, and various physician consults, the patient was diagnosed with anti-NMDAR encephalitis secondary to a paraneoplastic effect originating from an ovarian dermoid cyst., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Casarcia et al.)

Objective: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is frequently associated with ovarian teratomas. The diverse clinical presentations and several stages of disease development pose a significant diagnostic challenge for clinicians. The main objective of this research was to show the prevalence of neuropsychiatric symptoms of ovarian-teratoma-associated anti-NMDAR encephalitis and to highlight the importance of multidisciplinary collaboration in the diagnosis, treatment, and prevention of disease progression., Methods: Literature searches were carried out using PubMed, Scopus, and Web of Science Core Collection. The following data were retrieved: authors' names, year of publication, type of study, number and age of patients included, diagnostic methods of disease evaluation, prevalence of anti-NMDAR antibodies, psychiatric manifestations, other symptoms, initial diagnosis, treatment strategies, and histopathology results. Data analyses were performed and considered statistically significant when p  < 0.05., Results: Our study included 98 female patients with encephalitis associated with a teratoma. The study group reported specific symptoms more often than expected in the general population ( p  < 0.05). The incidence of seizures deviated most from rates in the general population. The major significant differences were observed in cases of psychosis, seizures, hypoventilation, aphasia, and coma., Conclusions: Teratoma-associated anti-NMDAR encephalitis diagnosis should be systematically investigated in patients presenting with first-time psychotic episodes. Prompt diagnosis and treatment are imperative for prevention of disease progression and better outcomes. Screening and identification of anti-NMDAR antibodies and considering the association of ovarian teratoma and neuropsychiatric symptoms suggesting encephalitis are critical for establishing the proper diagnosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background & objectives Acute encephalitic syndrome (AES), encompasses a wide spectrum of potential causes, clinical presentations, and outcomes. While infectious encephalitis is generally considered more prevalent, autoimmune encephalitis is emerging as a significant aetiology. Neuronal autoantibodies have been identified independently or in association with acute viral encephalitis. The primary objective of this study was to ascertain the prevalence and clinical manifestation of autoimmune encephalitis as well as of coexisting viral markers in children with AES. Methods This study was a prospective observational investigation conducted in a hospital setting. It involved enrolling children with AES who were admitted to specific tertiary hospitals. Children were subjected to examinations to detect the presence of viral markers and neuronal autoantibodies in both their blood and cerebrospinal fluid (CSF). All the participants received treatment based on established guidelines and was followed for six months for outcome assessment. Results During the study period, 867 children with AES were examined. Among these cases, 37 children (4.2%) were diagnosed with autoimmune encephalitis, and all of them tested positive for anti-NMDAR (N-methyl-D-aspartate receptor) antibodies. Evidence of viral infection was seen in 409 (47.1%) of cases, out of which nearly 254 (29.2%) children had detectable HSV IgM antibodies. Among the 37 children with autoimmune encephalitis, 25 (67.5%) had evidence of a viral trigger, with eight of them tested positive for HSV IgM antibodies. The clinical presentation of autoimmune-associated AES was similar to those with viral aetiology. Interpretation & conclusions Autoimmune encephalitis triggered by neurotropic (HSV) viral infection was more prevalent in this study than in the earlier reports. Typically, these children show positive responses to immunosuppressive treatments if administered promptly. It is hence advisable to assess children who exhibit behavioural issues and movement disorders for possible autoimmune encephalitis.

Aim: Anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis is one of the autoimmune encephalitis, which often occurs in children and young adults, especially in young women. In addition to viral infection, teratoma is an important causative factor. Anti‐NMDAR encephalitis is well known to neurologist. However, this is less well known to gynecologists, who may have a decisive role in etiological management. Therefore, from the perspective of gynecologists, we provide an overview of the relationship between the encephalitis and ovarian teratoma, the clinical features and treatment of this disease, and prognosis of pregnant women with this encephalitis. Methods: We searched the PubMed database using the search terms in various combinations "teratoma," "dermoid cyst," "ovary," "ovarian," "anti‐NMDAR encephalitis," and "N‐methyl‐D‐aspartate receptor." Results: According to the current literature, the mechanism of anti‐NMDAR encephalitis is probably due to the ectopic expression of the NMDAR in the teratomas tissue. The disease has a high mortality rate if not treated promptly and effectively. An important way to improve patients' outcome is to remove the ovarian tumor in time. Pregnant women are also at risk of developing anti‐NMDAR encephalitis during pregnancy. The fetal outcome is usually better in patients with mid‐ to late‐pregnancy onset than in early pregnancy, and patients are often able to maintain their pregnancies into late pregnancy. Conclusion: Young women with sudden onset of abnormal psychiatric behavior should be actively screened for ovarian tumors and, if confirmed to be teratoma‐associated anti‐NMDAR encephalitis, should undergo gynecologic surgery as early as possible, which can help improve their prognosis. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to (i) analyse the clinical characteristics, treatment outcome and long-term prognosis of anti-NMDAR encephalitis and (ii) study the differences between paediatric and adult patients. Methods: This was a chart review of all patients with anti-NMDAR encephalitis. Results: There were 28 patients with 18 patients belonging to the paediatric (<18 years) age group. There was female (94%) preponderance in the paediatric age group, while in adult patients, there was no gender predilection (p=0.006). There was no significant difference in clinical feature, outcome or number of relapses between paediatric and adult population groups. MRI brain was abnormal in 53% of patients. Among the 15 patients with MRI abnormalities at the onset, 53% had poor functional outcome at 1 year, while in 12 patients with normal initial MRI brain, only 8% had poor functional outcome at 1 year (p =0.01). Nearly 53% of patients with abnormal MRI at presentation had at least one clinical relapse within 2 years while in patients with normal MRI at presentation, 15% had a clinical relapse (p=0.037). EEG abnormalities were noticed in 71% of patients; among them, 40 and 15% had poor functional outcome at 1 and 2 years respectively. In comparison, those with normal first EEG at onset, 12% had poor functional outcome at 2 years (p=0.57). Conclusions: Both paediatric and adult patients presented with similar clinical features but the paediatric population had female preponderance. The functional outcome and number of relapse were comparable in both the paediatric and adult groups. Patients with parenchymal changes on MRI and abnormal EEG showed poorer response compared to those with normal MRI and/or EEG at the onset. Patients have lesser severity of symptoms at relapse than in the first episode. An early diagnosis and treatment are essential for better long-term functional outcome. [ABSTRACT FROM AUTHOR]

Anti-N-methyl-D-aspartate-receptor (A-NMDAR) encephalitis is the most common type of autoimmune encephalitis in the pediatric age group. It is known to be triggered by viral infections such as herpes simplex infections. However, A-NMDAR encephalitis with HIV infection is a very rare event, with cases reported mostly in adults. The current report is of a previously healthy child who presented with recurrent vomiting, irritability, visual impairment, and new onset complex partial seizures and right somatosensory seizures with generalization occurring in clusters. Over a period of 3 weeks, he developed rapidly progressive bilateral painless visual loss, visual hallucinations, and behavioral changes. Brain magnetic resonance imaging (MRI) showed predominantly cortical symmetrical T2/FLAIR hyperintense signal change in parieto-occipito-temporal regions. The serum and cerebrospinal fluid were strongly positive for anti-NMDAR antibodies, and he also tested positive for HIV-1 antibodies acquired by vertical transmission. The patient and mother tested positive for HIV antibodies for the first time. Repeat MRI revealed gliosis in the parieto-occipito-temporal regions, and hippocampi showed volume loss and T2/FLAIR hyperintense signal change in the posterior thalami with patchy hyperintensities in the right putamen. The seizures subsided with immunomodulation along with anti-epileptic drugs, but he had residual cortical visual impairment on follow-up. This is the first report of A-NMDAR encephalitis presenting as a harbinger of HIV infection in a child. This calls for testing for A-NMDAR antibodies in children with HIV infection presenting with neurological or neuropsychiatric manifestations. [ABSTRACT FROM AUTHOR]

Objective: Recent studies found that changes of thyroid antibodies (ATAbs), thyroid hormone, and non-thyroidal illness syndrome (NTIS) characterized by thyroid hormone inactivation with low triiodothyronine and high reverse triiodothyronine followed by suppressed thyroid-stimulating hormone (TSH) in adult anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis were associated with disease severity. This study aimed to explore thyroid function and ATAbs in pediatric anti-NMDAR encephalitis and their clinical association.Methods: We retrospectively analyzed the clinical data of 51 pediatric cases with anti-NMDAR encephalitis hospitalized in Guangzhou Women and Children's Medical Center from August 2016 to 2019.Results: A percentage of 52.9% of patients belonged to the ATAb (+) group, with 26 cases both positive for anti-thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin antibodies (TGAb), and one patient only positive for TPOAb. A percentage of 62.7% of patients had at least one abnormality in terms of FT3, free thyroxin (FT4), or TSH levels. Meanwhile, 45.1% of patients were diagnosed with NTIS. Among 25 cases retested for thyroid function 2 months after the initial test, the respectively decreased FT3 and FT4 in 13 and 11 cases on admission returned to normal or closer normal than before; TPOAb in eight cases and TGAb in 12 cases were changed from positivity to negativity. Compared with onset, the level of TPOAb and TGAb at relapse remained stable or significantly decreased, respectively. Compared with the ATAb (–) group, the ATAb (+) group had an older onset age, a higher ratio of movement disorders, elevated rate of sleep disorders, increased anti-nuclear antibody positivity rate, and higher ratio of more than one course of intravenous immunoglobulin treatment. There were no significant differences between the NTIS and non-NTIS groups in clinical characteristics.Conclusion: Anti-thyroid antibody positivity, abnormality of FT3, FT4, or TSH levels and NTIS are frequent in pediatric anti-NMDAR encephalitis. Thyroid antibody and thyroid hormone abnormalities could be improved through the course of treatment of anti-NMDAR encephalitis. Cases with ATAbs (+) are at older onset ages and more likely to be treated by intravenous immunoglobulin therapy more than once. Unlike adult anti-NMDAR encephalitis, NTIS might not be associated with the clinical characteristics of anti-NMDAR encephalitis in pediatric patients.

Objective: Recent studies found that changes of thyroid antibodies (ATAbs), thyroid hormone, and non-thyroidal illness syndrome (NTIS) characterized by thyroid hormone inactivation with low triiodothyronine and high reverse triiodothyronine followed by suppressed thyroid-stimulating hormone (TSH) in adult anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis were associated with disease severity. This study aimed to explore thyroid function and ATAbs in pediatric anti-NMDAR encephalitis and their clinical association. Methods: We retrospectively analyzed the clinical data of 51 pediatric cases with anti-NMDAR encephalitis hospitalized in Guangzhou Women and Children's Medical Center from August 2016 to 2019. Results: A percentage of 52.9% of patients belonged to the ATAb (+) group, with 26 cases both positive for anti-thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin antibodies (TGAb), and one patient only positive for TPOAb. A percentage of 62.7% of patients had at least one abnormality in terms of FT3, free thyroxin (FT4), or TSH levels. Meanwhile, 45.1% of patients were diagnosed with NTIS. Among 25 cases retested for thyroid function 2 months after the initial test, the respectively decreased FT3 and FT4 in 13 and 11 cases on admission returned to normal or closer normal than before; TPOAb in eight cases and TGAb in 12 cases were changed from positivity to negativity. Compared with onset, the level of TPOAb and TGAb at relapse remained stable or significantly decreased, respectively. Compared with the ATAb (–) group, the ATAb (+) group had an older onset age, a higher ratio of movement disorders, elevated rate of sleep disorders, increased anti-nuclear antibody positivity rate, and higher ratio of more than one course of intravenous immunoglobulin treatment. There were no significant differences between the NTIS and non-NTIS groups in clinical characteristics. Conclusion: Anti-thyroid antibody positivity, abnormality of FT3, FT4, or TSH levels and NTIS are frequent in pediatric anti-NMDAR encephalitis. Thyroid antibody and thyroid hormone abnormalities could be improved through the course of treatment of anti-NMDAR encephalitis. Cases with ATAbs (+) are at older onset ages and more likely to be treated by intravenous immunoglobulin therapy more than once. Unlike adult anti-NMDAR encephalitis, NTIS might not be associated with the clinical characteristics of anti-NMDAR encephalitis in pediatric patients. [ABSTRACT FROM AUTHOR]

This review article covers the vaccination related issues in autoimmune disorders of central nervous system (CNS) including narcolepsy, anti-NMDAR encephalitis, Rasmussen encephalitis and febrile infection related epilepsy syndrome (FIRES). Beyond these conditions the immune mediated epilepsies related with autoimmune CNS disorders are discussed and indications and contraindications of vaccinations in these cases are also considered. • This article highlights the most important aspect of modern neuroimmunology –autoimmune disorders, their mechanisms and relation to vaccination. • The most significant is to underlie if vaccination is allowed in children with autoimmune disorders. [ABSTRACT FROM AUTHOR]

Background: Growing evidence suggests an association between dyslipidemia and autoimmune diseases. This study aimed to perform a preliminary analysis to investigate the role of lipid profiles in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and to preliminarily explore the potential inflammatory effects of lipids on this disease by analyzing the association of lipid profiles with different inflammatory markers. Methods: This retrospective study consisted of 40 anti-NMDAR encephalitis patients and 74 healthy controls. Serum lipid profiles and different inflammatory markers were analyzed upon admission and at each follow-up. Lipid profiles were compared among subgroups of patients, which were divided according to clinical characteristics. Correlations between lipid profiles and different inflammatory markers were assessed. Results: The results showed that lipid profiles were abnormal and were correlated with both disease severity and prognosis in patients with anti-NMDAR encephalitis. Correlations between lipid profiles and different inflammatory markers were observed. After 12 months of treatment, inflammatory markers changed with lipid profiles, and these changes were significantly correlated. Conclusions: Lipid profiles are associated with pathogenesis and progression of anti-NMDAR encephalitis, and they are significantly correlated with different inflammatory markers, suggesting that the association of lipids with the disease might be influenced by the inflammatory response. [ABSTRACT FROM AUTHOR]

[Display omitted] • Excessive mitochondrial fission was demonstrated in mice model of anti-NMDAR encephalitis, leading to mitochondrial dysfunction. • Blockade of the autophagic flux was found in mice model of anti-NMDAR encephalitis, resulting in accumulation of the fragmented mitochondria. • The overactivated mTOR signaling pathway exerts dual regulation over mitochondrial fission and autophagy. • Rapamycin, the specific inhibitor of mTOR signaling pathway, alleviates mitochondrial dysfunction and behavioral disorders in anti-NMDAR encephalitis mice. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most prevalent forms of autoimmune encephalitis, characterized by a series of neurological and psychiatric symptoms, including cognitive impairment, seizures and psychosis. The underlying mechanism of anti-NMDAR encephalitis remains unclear. In the current study, the mouse model of anti-NMDAR encephalitis with active immunization was performed. We first uncovered excessive mitochondrial fission in the hippocampus and temporal cortex of anti-NMDAR encephalitis mice, indicated by elevated level of Phospho-DRP1 (Ser616) (p-Drp1-S616). Moreover, blockade of the autophagic flux was also demonstrated, leading to the accumulation of fragmented mitochondria, and elevated levels of mitochondrial reactive oxygen species (mtROS) and mitochondrial DNA (mtDNA) in anti-NMDAR encephalitis. More importantly, we found that the mTOR signaling pathway was overactivated, which could aggravate mitochondrial fission and inhibit autophagy, resulting in mitochondrial dysfunction. While rapamycin, the specific inhibitor of the mTOR signaling pathway, significantly alleviated mitochondrial dysfunction by inhibiting mitochondrial fission and enhancing autophagy. Levels of mtROS and mtDNA were markedly reduced after the treatment of rapamycin. In addition, rapamycin also significantly alleviated cognitive dysfunction and anxious behaviors found in anti-NMDAR encephalitis mice. Thus, our study reveals the vital role of mitochondrial dysfunction in pathological mechanism of anti-NMDAR encephalitis and lays a theoretical foundation for rapamycin to become a clinically targeted drug for anti-NMDAR encephalitis. [ABSTRACT FROM AUTHOR]

Abstract Encephalitis with anti-NMDAR antibodies (NMDAR-E) is a severe autoimmune neurological disorder, defined by a clinical presentation of encephalitis and the presence of IgG targeting the GluN1 subunit of NMDA receptors in the CSF. An underlying ovarian teratoma is commonly associated with this autoimmune disease suggesting a role of the tumor in immunopathogenesis. In this study, we characterized the salient histopathological features of 27 ovarian teratomas associated with NMDAR-E (3 immature and 24 mature teratomas) and 40 controls without associated encephalitis. All but one NMDAR-E-associated teratomas contained a nervous tissue component, while less than 40% of control teratomas did (p

Background: We investigated the potential use of SPECT quantification in addition to qualitative brain perfusion analysis for the detection of anti-NMDAR encephalitis. The question is how to normalize brain activity to be able to quantitatively detect perfusion patterns. Usually, brain activity is normalized to a structure considered unaffected by the disease. Methods: Brain [99mTc]-HMPAO SPECT was performed as a method to detect brain perfusion patterns. The patterns of abnormal brain perfusion cannot always be reliably and qualitatively assessed when dealing with rare diseases. Recent advances in SPECT quantification using commercial software have enabled more objective and detailed analysis of brain perfusion. The cerebellum and whole brain were used as the normalization structures and were compared with visual analysis. Results: The quantification analysis performed with whole brain normalization confirmed right parietal lobe hypoperfusion while also detecting statistically significant left-to-right perfusion differences between the temporal lobe and thalamus. Whole brain normalization further described bilateral frontal lobe hyperperfusion, predominantly of the left lobe, and was in accordance with visual analysis. Conclusion: SPECT quantitative brain perfusion analysis, using the whole brain as the normalization structure rather than the cerebellum, in this case, improved confidence in the visual detection of anti-NMDAR encephalitis and provided unexpected solutions to atypical psychiatric dilemmas.

BackgroundDisruption of the blood–brain barrier (BBB) is an important pathophysiological process of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. A recent multi-center study showed that soluble (s) CD146 is a potential biomarker for monitoring early BBB damage and central nervous system inflammation, but little is known about sCD146 in anti-NMDAR encephalitis.MethodTwenty-three anti-NMDAR encephalitis patients and seventeen controls with non-inflammatory neurological diseases were recruited. sCD146 and inflammatory cytokines in cerebrospinal fluid (CSF) and serum were detected by ELISA. Modified Rankin scale (mRS) scores were used to assess the neurological status of each patient. A follow-up review was completed three months after discharge.ResultssCD146 levels in the CSF of patients with the acute stage anti-NMDAR encephalitis were significantly increased compared with controls and accompanied by increases in TNF-α, IL-6 and IL-10. CSF sCD146 was positively correlated with neuroinflammatory factors in the CSF and with mRS score. Three months after effective treatment, CSF sCD146 in patients was significantly decreased but remained significantly different compared with the controls.ConclusionOur data suggested that higher expression of CSF sCD146 correlated with more serious neurological damage. Therefore, levels of CSF sCD146 may represent a promising indicator for monitoring disease and optimizing clinical treatment decisions in the early stages of anti-NMDAR encephalitis.

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been discovered for more than a decade, but the establishment of standardized immunotherapy protocol for pediatric patients still needs more clinical evidence.Methods: A multicenter, retrospective study was conducted on pediatric patients diagnosed with anti-NMDAR encephalitis between November 2011 and December 2018. The clinical records including clinical manifestations, immunotherapy strategies, and outcomes were collected and analyzed.Results: A total of 386 patients were included in our study and the median onset age was 8.00 (IQR 4.83–10.90) years. All patients received first-line immunotherapy and the majority (341, 88.3%) used the standard combination of methylprednisolone pulses (MEP) and intravenous immunoglobulins (IVIG), but 211 patients did not show satisfactory improvement (mRS ≥ 3). Mainly three treatment strategies were applied after first-line immunotherapy: second-line immunotherapy, repetitive first-line immunotherapy, and maintaining oral prednisolone. For patients with mRS ≥ 4 after first-line immunotherapy, the incidence of poor outcome (mRS ≥ 3) in oral prednisolone group was higher than that in other treatment groups (p = 0.039). No difference in complete recovery rate (mRS = 0) was found between patients receiving second-line and repetitive first-line immunotherapy, or patients using long-term and short-term prednisolone. Out of 149 patients who received anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab) test, 27 (18.12%) were positive. Patients with concomitantly positive MOG-Ab showed milder conditions compared to patients with typical anti-NMDAR encephalitis and were more inclined to relapses. We also identified female, MOG-Ab positive, and not receiving second-line and/or repetitive first-line immunotherapy were risk factors for relapses.Conclusions: For patients with mRS ≥ 4 after first-line immunotherapy and patients with concomitantly positive MOG-Ab, second-line immunotherapy is recommended. When second-line immunotherapy is not applicable, repetitive first-line immunotherapy can be considered as an option. Both second-line and repetitive first-line immunotherapy are beneficial to reduce relapse rate. The duration of sequential oral prednisolone can be shortened after fully evaluating patients' conditions.

Introduction Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder characterized by neuropsychiatric symptoms before progressing to seizures, complex movement disorder, autonomic dysfunction and hypoventilation. Objectives Presenting a review of the psychiatric manifestations of anti-NMDAR encephalitis. Methods Search on Pubmed® and Medscape® databases with the following keywords: “psychiatric”, “anti-NMDA receptor encephalitis” and “anti-NMDAR encephalitis”. We focused on data from systematic reviews and meta-analyzes. The articles were selected by the authors according to their relevance. Results Studies show that 77% to 95% of patients with anti-NMDAR encephalitis initially present psychiatric manifestations. Age and sex distribution are young women, and the frequency of cases is lower after 40 years of age. The most common psychiatric symptoms are agitation (59%) and psychotic symptoms (54%). The psychotic symptoms more common are visual (64%), auditory (59%) hallucinations and persecutory delusions (73%). Catatonia is described in 42% of patients. Antipsychotic treatment induces an adverse drug reaction (33%), the neuroleptic malignant syndrome represents 22% of the cases. Delays in distinguishing this disease from a psychiatric disorder can have serious complications, with a mortality of up to 25% in patients receiving limited or delayed immunotherapy. Conclusions It’s important to consider anti-NMDAR encephalitis in the differential diagnosis of patients with an acute onset psychosis or unusual psychiatric symptoms. Antipsychotic treatment should be use with caution when suspected or confirmed anti-NMDAR encephalitis. Without appropriate treatment, patients may suffer a protracted course with significant long-term disability or death. A clinical index of suspicion is required to identify patients who would benefit from cerebrospinal fluid testing and immunotherapies. Disclosure No significant relationships.

Background: Disruption of the blood–brain barrier (BBB) is an important pathophysiological process of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. A recent multi-center study showed that soluble (s) CD146 is a potential biomarker for monitoring early BBB damage and central nervous system inflammation, but little is known about sCD146 in anti-NMDAR encephalitis. Method: Twenty-three anti-NMDAR encephalitis patients and seventeen controls with non-inflammatory neurological diseases were recruited. sCD146 and inflammatory cytokines in cerebrospinal fluid (CSF) and serum were detected by ELISA. Modified Rankin scale (mRS) scores were used to assess the neurological status of each patient. A follow-up review was completed three months after discharge. Results: sCD146 levels in the CSF of patients with the acute stage anti-NMDAR encephalitis were significantly increased compared with controls and accompanied by increases in TNF-α, IL-6 and IL-10. CSF sCD146 was positively correlated with neuroinflammatory factors in the CSF and with mRS score. Three months after effective treatment, CSF sCD146 in patients was significantly decreased but remained significantly different compared with the controls. Conclusion: Our data suggested that higher expression of CSF sCD146 correlated with more serious neurological damage. Therefore, levels of CSF sCD146 may represent a promising indicator for monitoring disease and optimizing clinical treatment decisions in the early stages of anti-NMDAR encephalitis. [ABSTRACT FROM AUTHOR]

Aims: To explore large‐scale brain network alterations and examine their clinical and neuropsychological relevance in patients with anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis. Methods: Twenty‐four patients with anti‐NMDAR encephalitis and 26 matched healthy controls (HCs) were enrolled in our study. Based on the multimodal MRI dataset, individual morphological, structural, and functional brain networks were constructed and compared between the two groups at multiple levels. The associations with clinical/neuropsychological variables and the discriminant ability of significant alterations were further studied. Results: Multimodal network analysis revealed that anti‐NMDAR encephalitis mainly affected morphological and structural networks, but subtle alterations were observed in functional networks. Intriguingly, decreased network local efficiency was observed for both morphological and structural networks and increased nodal centrality in the lateral orbital gyrus was convergently observed among the three types of networks in the patients. Moreover, the alterations, particularly those from structural networks, accounted largely for cognitive deficits of the patients and could distinguish the diseased individuals from the HCs with excellent performance (area under the curve =0.933). Conclusions: The current study provides a comprehensive view of characteristic multimodal network dysfunction in anti‐NMDAR encephalitis, which is crucial to establish new diagnostic biomarkers and promising therapeutic targets for the disease. [ABSTRACT FROM AUTHOR]

Purpose: Ovarian teratoma-associated anti-N-methyl-d-aspartate receptor encephalitis is a rare disease with uncertain etiology and pathogenesis. The disorder is severe and rare with a great impact on young adults. This study aimed to improve the awareness of the disease from experience in our single center. Methods: Between July 2012 and December 2019, six patients with ovarian teratoma-associated anti-N-methyl-d-aspartate receptor encephalitis were enrolled in Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. All patients' data like manifestations, laboratory and radiological data, treatment, and follow-up were reviewed. Results: Typical psychotic symptoms, memory, and consciousness disorders accompanied by seizures were observed in all patients from this study. All six patients showed positive signals in serum and cerebrospinal fluid samples for N-methyl-d-aspartate receptor and received immunotherapy. Three patients underwent unilateral oophorocystectomy and the other three underwent unilateral oophorectomy through minimally invasive surgeries, including laparoscopic and single-port laparoscopic surgeries. The median follow-up time 24.5 months (range from 6 to 93 months). No death occurred. Two patients had recurrent psychotic symptoms while the left four patients had no mental symptoms or tumor recurrence during postoperative follow-up. Conclusions: For patients with clinical manifestations of unexplained acute psychiatric symptoms accompanied by seizures, memory, and consciousness disorders, the possibility of anti-N-methyl-d-aspartate receptor encephalitis should be considered. To confirm the diagnosis, examinations of anti-N-methyl-d-aspartate receptor antibodies need to be completed as early as possible. Immunotherapy and tumor location should be given in time once the diagnosis is defined. We recommended removing the tumor as soon as possible without concerning whether the patient is in the acute phase or not. The surgical procedure should be decided based on pathology, age, fertility desire, and patients' requirements and it should be ensured that tumors are completely removed during operation. Postoperative follow-up is particularly important. [ABSTRACT FROM AUTHOR]

Introduction: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disease associated with the NMDA receptor. This paper describes a patient who presented with bilateral hearing loss as the initial symptom of anti-NMDAR encephalitis.Case Report: We describe a 31-year-old young female with anti-NMDAR encephalitis who presented with bilateral severe hearing loss after brief loss of consciousness and then accompanied by other symptoms, such as generalized tonic–clonic seizures, manic episodes, excessive salivation, severe cognitive impairment, and complex non-convulsive status epilepticus. Great improvement was achieved by a combined treatment of steroid, IVIG, and plasmapheresis, especially after surgical removal of the ovarian teratoma. When she was discharged on hospital day 43, her hearing loss obtained a significant improvement.Conclusion: This case study and literature review investigated the impairment of hearing loss and its subsequent treatment in patients with anti-NMDAR encephalitis.

Abstract Objective We reviewed the psychotic symptoms of anti‐NMDA receptor encephalitis (NMDARE) to differentiate its presentation from those found in a primary psychiatric disorder. We hypothesized that the cycloid psychosis (CP) phenotype would be a frequent clinical presentation in the psychiatric phase of NMDARE. Method A systematic literature review in PubMed of all case reports published on NMDARE was performed from database inception to March 2020. We included all cases where psychotic symptoms were reported and whose diagnoses were confirmed by the presence of anti‐NMDAR antibodies in the cerebrospinal fluid (CSF). An email including a short test (CP phenotype, Perris and Brockington's criteria) was sent to all case report authors asking them to describe the psychotic symptoms. Results We identified 335 case reports fulfilling our criteria, and the authors of 200 replied. Our analyses were based exclusively on those answers and data extracted from the articles. Median patient age was 25 years (+‐11.4), 81% were female, and 39% had an ovarian teratoma. A complete CP phenotype was identified in 175 patients (87%). These were acute psychotic episodes with a sudden onset and a fluctuating clinical pattern mostly characterized by confusion (97%), delusions (75%), hallucinations (69%), motility disturbances (87%), and mood oscillations (80%). Conclusion The complete CP phenotype was frequently the expression of psychotic symptoms in NMDARE. We suggest that patients with a first psychotic episode who initially exhibit the CP phenotype should undergo CSF analysis to determine whether antibodies against neuronal cell surface or synaptic receptors are present to rule out a possible diagnosis of autoimmune encephalitis.

Introduction: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, a serious neurological autoimmune disorder caused by autoantibodies with diverse clinical manifestations, may simultaneously onset with antimyelin oligodendrocyte glycoprotein (MOG) demyelination after recurrent central nervous system (CNS) demyelination.Case Report: We present a case of anti-NMDAR encephalitis combining with anti-MOG CNS demyelination following recurrent CNS demyelination. A 38-year-old man admitted to hospital developed epileptic seizures following recurrent episodes of cross-sensory disturbance and dizziness. Magnetic resonance imaging (MRI) showed a demyelinating lesion in the right brainstem initially. Despite a good response to methylprednisolone pulse therapy at the beginning, the patient still had relapses and progression after corticosteroid reduction or withdrawal. Then brain MRI discovered new serpentine lesions involving extensive cerebral cortex on his second relapse. Repeat autoantibodies test indicated cerebrospinal fluid (CSF) NMDAR antibodies coexisted with MOG-Abs simultaneously, suggesting the diagnosis of anti-NMDAR encephalitis with anti-MOG CNS demyelination.Results: After a definite diagnosis, the patient was treated with mycophenolate mofetil (MMF) and corticosteroid. He was discharged after his symptoms ameliorated. No neurological sequels remained, and there were no effects on his activities of daily living after 6 months of immunoregulatory therapy of MMF and corticosteroid.Conclusion: For individuals with recurrent CNS demyelination, especially combining with cortical encephalitis, repeated detection of autoantibodies against AE, and demyelination in CSF/serum can be helpful to enable a definite early diagnosis. For patients who suffer from anti-NMDAR encephalitis combining with anti-MOG CNS demyelination, second-line immunotherapy is recommended when first-line treatment such as steroids, intravenous immunoglobulin G (IVIG) and plasma exchange has been proven ineffective to prevent the relapse of disease.