Neuropsychiatric manifestations of anti-N-methyl-D-aspartate receptor encephalitis in a 14-year-old female: A case report.

Key Clinical Message: This case underscores the critical importance of timely recognition and management of NMDAR encephalitis in adolescents to mitigate potential long-term sequelae. If a pediatric patient presents with suspected viral encephalitis, autoimmune etiology must be excluded via cerebrospinal fluid antibody assay to guide appropriate immunosuppressive therapy, and improve patient outcomes. Abstract: Autoimmune encephalitis particularly involving the n-methyl-d-aspartate receptor (NMDAR) is recognized as a rare cause of acute encephalopathy in pediatric patients. The following case is of a 14-year-old female diagnosed with anti-NMDAR encephalitis who initially presented with fever, episodic convulsions, and loss of consciousness. She subsequently developed right-sided body weakness, expressive aphasia, and visual hallucinations. Clinical examination revealed prominent neuropsychiatric manifestations such as altered sensorium, motor deficits, hallucinations, and visual disturbances. Cerebello-bulbar signs were not appreciable in this particular case. She was treated for viral encephalitis but showed no improvement. Laboratory investigations revealed the presence of NMDAR antibodies in the cerebrospinal fluid confirming the diagnosis of autoimmune etiology. The patient demonstrated notable improvement following immunosuppressive treatment.

Reversible splenial lesion syndrome in Anti-N-methyl-D-aspartate receptor encephalitis.

Here we described an 18-year-old woman who were initially misdiagnosed as psychiatric disorders in a psychiatric institution. She was transferred to our neurological ward because of impaired consciousness. Neuronal antibody testing confirmed the diagnosis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Cerebral magnetic resonance imaging (MRI) revealed a concomitant disorder named reversible splenial lesion syndrome (RESLES). After administration of combined immunotherapy, the patient recovered completely 3 months after discharge. To our knowledge, co-occurrence of RESLES and anti-NMDAR encephalitis was only described in two patients with teratoma and we provide another case without teratoma. We highlight that anti-NMDAR antibodies can be added to the multiple causes of RESLES. It is therefore imperative for clinicians to detect anti-neuronal antibodies in patients with RESLES to avoid missed diagnosis.

Hippocampal hub failure is linked to long-term memory impairment in anti-NMDA-receptor encephalitis: insights from structural connectome graph theoretical network analysis.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is characterized by distinct structural and functional brain alterations, predominantly affecting the medial temporal lobes and the hippocampus. Structural connectome analysis with graph-based investigations of network properties allows for an in-depth characterization of global and local network changes and their relationship with clinical deficits in NMDAR encephalitis. METHODS: Structural networks from 61 NMDAR encephalitis patients in the post-acute stage (median time from acute hospital discharge: 18 months) and 61 age- and sex-matched healthy controls (HC) were analyzed using diffusion-weighted imaging (DWI)-based probabilistic anatomically constrained tractography and volumetry of a selection of subcortical and white matter brain volumes was performed. We calculated global, modular, and nodal graph measures with special focus on default-mode network, medial temporal lobe, and hippocampus. Pathologically altered metrics were investigated regarding their potential association with clinical course, disease severity, and cognitive outcome. RESULTS: Patients with NMDAR encephalitis showed regular global graph metrics, but bilateral reductions of hippocampal node strength (left: p = 0.049; right: p = 0.013) and increased node strength of right precuneus (p = 0.013) compared to HC. Betweenness centrality was decreased for left-sided entorhinal cortex (p = 0.042) and left caudal middle frontal gyrus (p = 0.037). Correlation analyses showed a significant association between reduced left hippocampal node strength and verbal long-term memory impairment (p = 0.021). We found decreased left (p = 0.013) and right (p = 0.001) hippocampal volumes that were associated with hippocampal node strength (left p = 0.009; right p < 0.001). CONCLUSIONS: Focal network property changes of the medial temporal lobes indicate hippocampal hub failure that is associated with memory impairment in NMDAR encephalitis at the post-acute stage, while global structural network properties remain unaltered. Graph theory analysis provides new pathophysiological insight into structural network changes and their association with persistent cognitive deficits in NMDAR encephalitis.

Anti-LGI1 encephalitis preceded by psychiatric symptoms: A case report.

Background: To date, only a few reports of anti-LGI1 encephalitis with isolated psychiatric symptoms in the initial phase have been reported. We present a relatively rare case of antileucine-rich glioma-inactivated 1 (LGI1) encephalitis that developed only psychiatric symptoms at the onset. Case Presentation: The patient was a male in his 40s who developed anxiety and panic symptoms and was started on antidepressants after being diagnosed with panic disorder by a psychiatrist. He visited our hospital 2 months later presenting with hallucinations, delusions, mild cognitive decline, and faciobrachial dystonic seizures in the left upper extremity and face. Fluid-attenuated inversion recovery magnetic resonance imaging revealed swelling and hyperintensities in the right caudate nucleus and putamen. Cerebrospinal fluid analysis did not show increased protein levels or cell counts and revealed positive oligoclonal bands. Subsequently, positive results for anti-LGI1 antibodies were observed in the cerebrospinal fluid. Therefore, the patient was diagnosed with anti-LGI1 encephalitis. Conclusion: This case highlights the need to consider anti-LGI1 encephalitis therapy in patients with acute-onset psychiatric symptoms.

Antibody-secreting cells as a source of NR1-IgGs in N-methyl-D-aspartate receptor-antibody encephalitis.

BACKGROUND: The pathogenicity of NR1-IgGs in N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis is known, but the immunobiological mechanisms underlying their production remain unclear. METHODS: For the first time, we explore the origin of NR1-IgGs and evaluate the contribution of B-cells to serum NR1-IgGs levels. Peripheral blood mononuclear cells (PBMCs) were obtained from patients and healthy controls (HCs). Naïve, unswitched memory (USM), switched memory B cells (SM), antibody-secreting cells (ASCs), and PBMC depleted of ASCs were obtained by fluorescence-activated cell sorting and cultured in vitro. RESULTS: For some patients, PBMCs spontaneously produced NR1-IgGs. Compared to the patients in PBMC negative group, the positive group had higher NR1-IgG titers in cerebrospinal fluid and Modified Rankin scale scores. The proportions of NR1-IgG positive wells in PBMCs cultures were correlated with NR1-IgGs titers in serum and CSF. The purified ASCs, SM, USM B cells produced NR1-IgGs in vitro. Compared to the patients in ASCs negative group, the positive group exhibited a worse response to second-line IT at 3-month follow-up. Naïve B cells also produce NR1-IgGs, implicating that NR1-IgGs originate from naïve B cells and a pre-germinal centres defect in B cell tolerance checkpoint in some patients. For HCs, no NR1-IgG from cultures was observed. PBMC depleted of ASCs almost eliminated the production of NR1-IgGs. CONCLUSIONS: These collective findings suggested that ASCs might mainly contribute to the production of peripheral NR1-IgG in patients with NMDAR-antibody encephalitis in the acute phase. Our study reveals the pathogenesis and helps develop tailored treatments (eg, anti-CD38) for NMDAR-antibody encephalitis.

The relevance of anti-N-methyl-D-aspartate receptor encephalitis for psychiatrists.

Psychiatrists are often the first to be consulted in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. While this disease is rare, psychiatrists need to be aware of its relevant fundamental, clinical and therapeutic aspects. We begin by reviewing the connection between anti-NMDAR encephalitis and the glutamate hypothesis of schizophrenia. Next, we focus on the profile of the patient typically afflicted with this disease. Then, we tackle the limited utility of current diagnostic criteria during the early stage of the disease. After reviewing the psychiatric features, we debate the quest for finding specific psychiatric phenotypes that could facilitate early-stage diagnosis. We conclude by discussing the treatment of psychiatric symptoms and disease outcomes. As follows, this paper presents the relevance of anti-NMDAR encephalitis for psychiatrists.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an essential differential diagnosis in Psychiatry, particularly when dealing with first-episode psychosis.Psychiatrists are often the first to be consulted in patients with NMDAR encephalitis, so they need to be aware of the relevant fundamental, clinical and therapeutic aspects of this disease.

Antibody-positive autoimmune encephalitis and paraneoplastic neurological syndrome: A Swedish case series.

OBJECTIVE: This study aimed to explore the clinical characteristics and temporal disease course of patients with autoimmune encephalitis (AE) and paraneoplastic neurological syndrome (PNS) in Sweden. METHODS: Thirty-seven antibody-positive AE and PNS cases were identified in the Healthcare region Mid Sweden between 2015 and 2019. Clinical data were collected through a retrospective review of electronic health records. Patients were divided into three subgroups based on antibody type: neuronal surface antibodies (NSAbs), onconeural antibodies, and anti-GAD65 antibodies. RESULTS: Nineteen patients had NSAbs, 11 onconeural antibodies, and seven anti-GAD65 antibodies. Anti-LGI1 and anti-NMDAR were the most frequently detected NSAbs, with anti-NMDAR cases having an older-than-expected age distribution (median age 40, range 17-72). Only 11 of 32 (30%) of patients had findings suggesting encephalitis on initial MRI, but 28 of 31 (90%) had pathological findings on initial cerebrospinal fluid analysis. All patients but one had abnormal EEG findings. Median time to immunotherapy was comparable among the three subgroups, whereas patients with anti-LGI1, anti-CASPR2, and anti-IgLON5 had an eightfold longer time to immunotherapy than anti-NMDAR and anti-GABA-B (p = .0016). There was a seasonal variation in onset for patients with non-tumor-related NSAbs and anti-GAD65 antibodies, with most patients (72%) falling ill in spring or summer. CONCLUSION: Swedish patients with AE and PNS had similar clinical characteristics as previously described cohorts from other geographical regions except for anti-NMDAR encephalitis, with older onset than expected. The onset of non-tumor-related AE occurred predominantly in the warm seasons, and AE with a more insidious onset was associated with delayed treatment initiation.

FLAMES overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review.

BACKGROUND: In recent years, simultaneous or sequential occurrence of MOG antibody disease and anti-NMDAR encephalitis in the same patient has been reported with increasing frequency. Scholars refer to the overlapping occurrence of these two disorders as MOG antibody disease and anti-NMDAR encephalitis overlap syndrome (MNOS). Cortical T2-weighted fluid-attenuated inversion recovery (FLAIR) -hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) is a rare clinical phenotype of MOGAD in which cortical FLAIR high-signal lesions are unilateral, with little spread to the cortex and meninges bilaterally. Although cases of FLAMES have been consistently reported. However, to our knowledge, such cases of FLAMES combined with NMDARE are rare. CASE PRESENTATION: Here, we describe a case of FLAMES combined with anti-NMDARE. The patient was a young male, 29 years old, admitted to our hospital with isolated seizures, whose MRI showed unilateral thalamic and bilateral frontal and parietal leptomeningeal involvement. Since we were unaware of the possibility of bilateral meningo-cortical MOGAD manifestations, the case was initially diagnosed as viral encephalitis and was given antiviral therapy. The diagnosis was not clarified until anti-NMDAR-IgG and MOG-IgG positivity was detected in the cerebrospinal fluid and serum. The patient was then treated with high-dose corticosteroids and his symptoms responded well to the steroids. Therefore, this case expands the clinical spectrum of MNOS overlap syndrome. In addition, we describe the clinical features of MNOS by summarizing the existing literature and exploring the possible mechanisms of its immune response. CONCLUSIONS: Our case serves as a reminder to clinicians that when patients present with atypical clinical manifestations such as seizures, consideration should be given to MNOS and conduct testing for various relevant autoantibodies (including MOG abs) and viruses in both serum and cerebrospinal fluid, as it is easy to misdiagnose the disease as other CNS diseases, such as viral meningoencephalitis. This syndrome exhibits a high responsiveness to steroids, highlighting the critical importance of recognizing the clinical and neuroimaging features of this overlap syndrome for prompt diagnosis and treatment. Furthermore, it enriches the disease spectrum of MNOS.

Case report: Rapid recovery after intrathecal rituximab administration in refractory anti-NMDA receptor encephalitis: report of two cases.

Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is one of the most prevalent etiologies of autoimmune encephalitis. Approximately 25% of anti-NMDAR encephalitis cases prove refractory to both first- and second-line treatments, posing a therapeutic dilemma due to the scarcity of evidence-based data for informed decision-making. Intravenous rituximab is commonly administered as a second-line agent; however, the efficacy of its intrathecal administration has rarely been reported. Case summary: We report two cases of severe anti-NMDAR encephalitis refractory to conventional therapies. These patients presented with acute-onset psychosis progressing to a fulminant picture of encephalitis manifesting with seizures, dyskinesia, and dysautonomia refractory to early initiation of first- and second-line therapeutic agents. Both patients received 25 mg of rituximab administered intrathecally, repeated weekly for a total of four doses, with no reported adverse effects. Improvement began 2-3 days after the first intrathecal administration, leading to a dramatic recovery in clinical status and functional performance. At the last follow-up of 6 months, both patients remain in remission without the need for maintenance immunosuppression. Conclusion: Our cases provide evidence supporting the intrathecal administration of rituximab as a therapeutic option for patients with refractory anti-NMDAR encephalitis. Considering the limited penetration of intravenous rituximab into the central nervous system, a plausible argument can be made favoring intrathecal administration as the preferred route or the simultaneous administration of intravenous and intrathecal rituximab. This proposition warrants thorough investigation in subsequent clinical trials.

Functional connectivity changes of the hippocampal subregions in anti-N-methyl-D-aspartate receptor encephalitis.

The hippocampus plays an important role in the pathophysiological mechanism of Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Nevertheless, the connection between the resting-state activity of the hippocampal subregions and neuropsychiatric disorders in patients remains unclear. This study aimed to explore the changes in functional connectivity (FC) in the hippocampal subregions of patients with anti-NMDAR encephalitis and its association with clinical symptoms and cognitive performance. Twenty-three patients with anti-NMDAR encephalitis and 23 healthy controls (HC) were recruited. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans and completed clinical cognitive scales. Based on the Brainnetome Atlas, the rostral (anterior) and caudal (posterior) hippocampi of both the left and right hemispheres were selected as regions of interest (ROIs) for FC analysis. First, a one-sample t-test was used to observe the whole-brain connectivity distribution of hippocampal subregions within the patient and HC groups at a threshold of p < 0.05. The two-sample t-test was used to compare the differences in hippocampal ROIs connectivity between groups, followed by a partial correlation analysis between the FC values of brain regions with statistical differences and clinical variables. This study observed that the distribution of whole-brain functional connectivity in the rostral and caudal hippocampi aligned with the connectivity differences between the anterior and posterior hippocampi. Compared to the HC group, the patients showed significantly decreased FC between the bilateral rostral hippocampus and the left inferior orbitofrontal gyrus and between the right rostral hippocampus and the right cerebellum. However, a significant increase in FC was observed between the right rostral hippocampus and left superior temporal gyrus, the left caudal hippocampus and right superior frontal gyrus, and the right caudal hippocampus and left gyrus rectus. Partial correlation analysis showed that FC between the left inferior orbitofrontal gyrus and the right rostral hippocampus was significantly negatively correlated with the California Verbal Learning Test (CVLT) and Brief Visuospatial Memory Test (BVMT) scores. The FC between the right rostral hippocampus and the left superior temporal gyrus was negatively correlated with BVMT scores. FC abnormalities in the hippocampal subregions of patients with anti-NMDAR encephalitis were associated with cognitive impairment, emotional changes, and seizures. These results may help explain the pathophysiological mechanisms and clinical manifestations of anti-NMDAR encephalitis and NMDAR dysfunction-related diseases such as schizophrenia.

White matter microstructural alterations in patients with anti-N-methyl-D-aspartate receptor encephalitis: A tract-based spatial statistics study.

BACKGROUND: Cognitive impairment is common in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis; however, neural mechanisms underlying this impairment remain unclear. Diffusion tensor imaging (DTI) is a potential method for studying the condition of white matter fibers in patients with anti-NMDAR encephalitis, allowing for an analysis of the neuroimaging mechanisms of cognitive impairment in conjunction with cognitive scales. This study aimed to explore white matter microstructural alterations and their correlation with cognitive function in patients with anti-NMDAR encephalitis. METHODS: DTI data were collected from 22 patients with anti-NMDAR encephalitis (aged 29.00(19.75, 39.50) years; 12 males, 10 females) and 20 healthy controls (HCs) (aged 24.50(21.25, 32.00); 12 males, 8 females) matched for age, sex, and educational level. Changes in the white matter microstructure were analyzed using tract-based spatial statistics. Pearson correlation analysis was used to explore the correlation between white matter integrity and neuropsychological scores. RESULTS: Compared with HCs, patients with anti-NMDAR encephalitis showed decreased fractional anisotropy and increased mean diffusivity values in extensive white matter regions, which were associated with disease severity, memory, and executive and visuospatial functions. CONCLUSION: Widespread impairment of the structural integrity of the white matter in the brain is significantly associated with cognitive dysfunction in patients with anti-NMDAR encephalitis, providing neuroimaging evidence for studying the underlying mechanisms.

Anti-N-methyl-D-aspartate receptor-associated encephalitis: A review of clinicopathologic hallmarks and multimodal imaging manifestations.

Anti-N-methyl-D-aspartate receptor-associated encephalitis (NMDARE) is a rare immune-mediated neuroinflammatory condition characterized by the rapid onset of neuropsychiatric symptoms and autonomic dysfunction. The mechanism of pathogenesis remains incompletely understood, but is thought to be related to antibodies targeting the GluN1 subunit of the NMDA receptor with resultant downstream dysregulation of dopaminergic pathways. Young adults are most frequently affected; the median age at diagnosis is 21 years. There is a strong female predilection with a female sex predominance of 4:1. NMDARE often develops as a paraneoplastic process and is most commonly associated with ovarian teratoma. However, NMDARE has also been described in patients with small cell lung cancer, clear cell renal carcinoma, and other benign and malignant neoplasms. Diagnosis is based on correlation of the clinical presentation, electroencephalography, laboratory studies, and imaging. Computed tomography, positron emission tomography, and magnetic resonance imaging are essential to identify an underlying tumor, exclude clinicopathologic mimics, and predict the likelihood of long-term functional impairment. Nuclear imaging may be of value for prognostication and to assess the response to therapy. Treatment may involve high-dose corticosteroids, intravenous immunoglobulin, and plasma exchange. Herein, we review the hallmark clinicopathologic features and imaging findings of this rare but potentially devastating condition and summarize diagnostic criteria, treatment regimens, and proposed pathogenetic mechanisms.

Anti-NMDA receptor encephalitis presenting as a progression of disease in a patient with underlying congenital leukodystrophy: Case report.

Anti-NMDA Receptor (NMDAR) Encephalitis (NMDARE) is an autoimmune disorder that is often debilitating and difficult to diagnose. Patients, especially those with underlying neuropsychiatric disorders, may experience delayed or misdiagnosis of NMDARE. Here, we report on a patient with known congenital leukodystrophy (CLD) and epilepsy with a challenging diagnosis of NMDARE. The patient first presented with progressive behavior changes and seizure-like episodes. Initial workup, including video EEG and brain MRI, were mostly unremarkable, and the patient's symptoms were resistant to treatment with multiple anti-epileptic drugs. Given the patient's complicated clinical history, his presentation was initially thought of as progression or exacerbation of his chronic disease. With continued lack of improvement, autoimmune encephalitis was considered. The patient was started on immunotherapy and autoimmune encephalitis panels were sent, which came back positive. He continued to improve over the next weeks and months. Despite a growing body of literature, our knowledge on confirmed risk factors for NMDAR remains limited outside of young age, ovarian teratomas, and herpes encephalitis. We know that maintenance of the blood brain barrier is key to preventing autoimmune disorders of the central nervous system (CNS), and multiple congenital leukodystrophies exhibit pathology in the neurovascular unit. This is the first described case of anti-NMDA receptor encephalitis in a patient with an underlying congenital leukodystrophy, which may reflect an underreported NMDAR encephalitis risk factor. With limited known risk factors and time to diagnosis and treatment so important, this case may reflect an important and underreported risk factor for NMDAR.

Disease course and psychosocial outcome for children and adolescents with anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVES: Explore psychosocial outcome and impact of persisting deficits on quality of life (QoL) and global functioning after anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) in children and adolescents. METHODS: Four female patients (age 7-16y) and their caregivers participated in the study. Information was collected from the medical records and the caregivers via a questionnaire. Both the patients and their caregivers were interviewed by means of the structured clinical interview for DSM-5 disorders, junior version (SCID-5 junior). CGAS and mRS scores were defined and the Pediatric Quality of Life Inventory (PedsQL) was used to assess quality of life of patients and caregivers. RESULTS AND CONCLUSION: After the acute phase of the disease patients go through a post-acute phase in which several persisting physical, cognitive and psychiatric symptoms gradually resolve during the following months to a year. In long-term follow up these symptoms partly resolved, but deficits persisted on several domains. Psychiatric symptoms, fatigue and mild cognitive deficits were present in three out of four patients at current assessment. In three patients their academic trajectory was altered. These deficits can have an impact on the quality of life and the global functioning of the patients and caregivers.

Electroconvulsive therapy for catatonia in anti-NMDA receptor encephalitis: A case series.

BACKGROUND: Anti-NMDAR encephalitis is the most common cause of immune-mediated catatonia. CASE SERIES: Three females presented with neuropsychiatric symptoms and were empirically treated with first-line immunotherapy and ovarian teratoma resection for suspected autoimmune encephalitis, preceding diagnostic confirmation via NMDAR antibody positivity. They required escalating large doses of benzodiazepines for refractory malignant catatonia resulting in ICU level care. ECT treatments were initiated, and patients were gradually noted to have clinical improvement as was measured by the Bush-Francis Catatonia Rating Scale. CONCLUSIONS: Clinicians should recognize catatonia among patients with suspected anti-NMDAR encephalitis and consider the early implementation of ECT into treatment algorithms.

Systematic review: clinical characteristics of anti-N-methyl-D-aspartate receptor encephalitis.

Background: The number of reported cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis has gradually increased since its discovery in 2007, while there are no uniform treatment guidelines. Objective: To summarize the clinical characteristics of patients with anti-NMDAR encephalitis and to analyze the factors affecting the disease prognosis. Methods: A systematic analysis of medical records was conducted, and PubMed, Embase, and Cochrane Library were searched from January 1, 2011, to December 31, 2021. Data were extracted, analyzed, and recorded in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Results: This study included 472 case reports. Most patients had prodromal symptoms of about 2 weeks, including psychiatric symptoms (53.2%), flu-like symptoms (51.5%), and seizures (23.9%), among others. Poor prognoses were associated with patients who had autonomic instability (p = 0.010), central hypoventilation (p = 0.014), and ICU support (p = 0.002). Patients with a higher age of onset were more likely to develop central hypoventilation (OR 1.024, CI 1.006-1.042, p = 0.009), cognitive impairment (OR 1.023, CI 1.009-1.037, p = 0.001), and memory impairment (OR 1.034, CI 1.017-1.050, p < 0.001), whereas patients with a lower age were more likely to have seizures (OR 0.979, CI 0.965-0.993, p = 0.003). In this study, 97.0% of patients received immunotherapy, with the most commonly used treatment regimen being intravenous methylprednisolone (IVGC) and intravenous immunoglobulin (IVIG). When compared with other treatment regimens, the IVGC+IVIG regimen (p < 0.001) resulted in better prognoses. Conclusion: When encountering patients with fever, headache, and initial psychiatric symptoms of unknown etiology, clinicians should test their CSF for antibodies to distinguish autoimmune encephalitis. Patients with autonomic instability, central hypoventilation, and ICU support had poorer prognoses. Clinicians should be aware that older patients are more likely to develop central hypoventilation, cognitive impairment, and memory impairment, while younger patients are more likely to develop seizures. The IVGC+IVIG treatment regimen has better prognoses than others. This study includes case reports, which have obvious selection bias, and there are no unified standards to measure the severity of the disease. Therefore, in the future, larger samples and randomized controlled trials are needed to evaluate the efficacy of different treatment regimens.

Autoimmune receptor encephalitis in ApoE­/­ mice induced by active immunization with NMDA1.

Subacute progressive neuropsychiatric symptoms with cognitive and motor impairment and autoimmune seizures are some of the typical symptoms of anti­N­methyl­D­aspartate receptor (anti­NMDAR) encephalitis. The mechanisms underlying this disease are yet to be elucidated, which could be partly attributed to the lack of appropriate animal models. The present study aimed to establish an active immune mouse model of anti­NMDAR encephalitis. Mice were immunized with the extracellular segment of the NMDA1 protein, then subjected to open­field and novel object recognition experiments. Plasma was collected after euthanasia on day 30 after immunization and anti­NMDA1 antibodies were detected using ELISA. Furthermore, brain slices were analyzed to measure postsynaptic density protein 95 (PSD­95) and NMDA1 expression. Western blot analysis of NMDA1 and PSD­95 protein expression levels in the hippocampus was also performed. In addition, protein expression levels of PSD­95 and NMDA1 in mouse neuronal HT­22 cells were evaluated. Compared with controls, mice immunized with NMDA1 exhibited anxiety, depression and memory impairment. Moreover, high anti­NMDA1 antibody titers were detected with ELISA and the levels of anti­NMDA1 antibody reduced postsynaptic NMDA1 protein density in the mouse hippocampus. These findings demonstrated the successful construction of a novel mouse model of anti­NMDAR encephalitis by actively immunizing the mice with the extracellular segment of the NMDA1 protein. This model may be useful for studying the pathogenesis and drug treatment of anti­NMDAR encephalitis in the future.

Pediatric anti-NMDAR encephalitis with demyelination on brain MRI: A single center study.

OBJECTIVE: To explore the clinical characteristics, immunotherapy response, and prognosis of pediatric anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis associated with demyelination on brain magnetic resonance (MRI). METHODS: We retrospectively reviewed the medical records of children diagnosed with anti-NMDAR encephalitis in our hospital between January 2016 and December 2021. All children with evidence of demyelination on brain MRI were included. RESULTS: A total of 183 anti-NMDAR encephalitis children were included; 8.7 % (16/183) of them had demyelination on brain MRI. Nine were positive for myelin oligodendrocyte glycoprotein (MOG)-IgG, while two were positive for both MOG-IgG and glial fibrillary acidic protein (GFAP)-IgG. Four patients had a history of acquired demyelinating syndromes and encephalitis, respectively, while nine (56.3 %) had atypical symptoms of anti-NMDAR encephalitis. All children had supratentorial demyelination on brain MRI; four of them had additional infratentorial lesions. All children received first-line immunotherapy; four were administered repeated first-line immunotherapy and/or rituximab because of poor initial response. During the follow-up, 37.5 % (6/16) of the children relapsed, but all responded well to immunotherapy. There were no significant differences in mRS score before immunotherapy, response to first-line immunotherapy, and long-term prognosis between anti-NMDAR encephalitis children with and without demyelination. However, patients with demyelination were more likely to have a history of acquired demyelinating syndromes or unexplained cortical encephalitis and to relapse. CONCLUSION: Pediatric anti-NMDAR encephalitis can co-occur with demyelination and has a high rate of MOG-IgG positivity. A history of acquired demyelinating syndromes or unexplained cortical encephalitis and atypical symptoms may indicate demyelination in children with anti-NMDAR encephalitis. Pediatric anti-NMDAR encephalitis with demyelination is more likely to relapse and needs a closer follow-up. However, it remains unknown whether more intensive immunotherapy is required in these patients.

Cerebrospinal fluid uric acid levels associated with disease severity in patients with anti-N-methyl-d-aspartate receptor encephalitis.

INTRODUCTION: Uric acid (UA) is an important natural antioxidant and strong peroxynitrite scavenger, but little is known about central nervous system (CNS) levels of UA in patients with anti-N-methyl-d-aspartate receptor encephalitis (NMDARE). METHODS: Cerebrospinal fluid (CSF) and serum levels of UA were determined in 72 patients with anti-NMDARE and 111 controls with non-inflammatory neurological diseases (NINDs). Serum UA levels were also evaluated in 132 healthy controls (HCs). CSF neuron-specific enolase (NSE) and blood-brain barrier (BBB) index were evaluated in patients with anti-NMDARE. The association of CSF UA levels with anti-NMDARE and its clinical parameters were evaluated in the patients. RESULTS: CSF UA levels were lower in patients with anti-NMDARE than in patients with NINDs, especially in patients with severe impairments (modified Rankin Scale [mRS] scores >3 vs. ≤ 3, p = 0.006). Furthermore, serum UA levels in patients with anti-NMDARE were significantly lower than in patients with NINDs and HCs. CSF UA levels were significantly associated with mRS scores, and serum UA levels in patients with anti-NMDARE. Furthermore, CSF/serum UA ratio was significantly associated with BBB index. CONCLUSIONS: CSF UA levels associated with disease severity and serum UA levels in patients with anti-NMDARE. And CSF/serum UA ratio correlated with BBB index, indicating that CSF and serum UA levels change similarly with BBB permeability in anti-NMDARE patients.