Search

Abstract Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder with a variety of clinical manifestations. It has been established that anti-NMDAR encephalitis may be related to ovarian teratoma in female patients. However, a considerable number of patients have no obvious evidence of ovarian teratoma during the onset of the disease. Case A 25-year-old previously-healthy female experienced a series of acute symptoms within two days, including confusion, disorientation, short-term memory loss, auditory hallucinations, abnormal behavior, refractory status epilepticus, etc. Her brain MRI and abdominal imaging showed no definite abnormality while her electroencephalogram exhibited the presence of low to moderate amplitude sharp, spike, and multi-spike waves. Serum and cerebrospinal fluid tests yielded positive results for anti-NMDAR antibodies. However, an ultrasound scan failed to identify an ovarian teratoma. Consequently, the diagnosis of anti-NMDAR encephalitis without teratoma was made after 4 days onset. After the plasma exchange and immunoglobulin therapy, her neurological symptoms improved and obtained a clinical cure. In the next eight months of follow-up, the patient accidentally touched a lump in the lower abdomen without any symptoms, and abdominal ultrasound and CT scan revealed a left ovarian tumor. Then she underwent left ovarian teratoma resection surgery and histopathology showed a mature cystic teratoma with neural components. The patient continued to receive five years of follow-up, and her condition remained stable without any recurrence, except that there had been a low titer of anti-NMDAR antibody in her serum. Conclusion Our case demonstrated the importance of long-term follow-up for female patients with anti-NMDAR encephalitis, since anti-NMDAR encephalitis-associated ovarian teratomas may develop in a delayed manner, even without any symptoms.

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

BackgroundEncephalitis associated with antibodies against the N-methyl-D-aspartate receptor (NMDAR) results in a distinctive neuro-psychiatric syndrome. It has been reported that the serum phenylalanine-tyrosine (Phe/Tyr) ratio increases during infection. However, the connection between phenylalanine-tyrosine metabolism and psychiatric symptoms remains unclear.MethodsWe enrolled 24 individuals with anti-NMDAR encephalitis and 18 individuals with non-inflammatory neurological diseases (OND). Chromatography was used to measure serum levels of phenylalanine and tyrosine. Serum and cerebrospinal fluid (CSF) TNF-α levels were obtained from the clinical database. The modified Rankin Scale (mRS) score and Glasgow Coma Scale (GCS) score were recorded during the acute phase. The area under the curve (AUC) of the receiver operating characteristic curve was used to assess prediction efficacy.ResultsIn NMDAR patients, levels of serum Phe and the ratio of serum Phe/Tyr were higher compared to OND patients. The serum Phe/Tyr ratio was also elevated in NMDAR patients with psychiatric syndrome. Furthermore, serum Phe and Tyr levels were correlated with inflammatory indexes.ConclusionThe serum Phe/Tyr ratio is elevated in NMDAR patients with psychiatric syndrome and is associated with severity. Therefore, the serum Phe/Tyr ratio may serve as a potential prognostic biomarker.

Abstract Background The pathway involving PTEN-induced putative kinase 1 (PINK1) and PARKIN plays a crucial role in mitophagy, a process activated by artesunate (ART). We propose that patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis exhibit insufficient mitophagy, and ART enhances mitophagy via the PINK1/PARKIN pathway, thereby providing neuroprotection. Methods Adult female mice aged 8–10 weeks were selected to create a passive transfer model of anti-NMDAR encephalitis. We conducted behavioral tests on these mice within a set timeframe. Techniques such as immunohistochemistry, immunofluorescence, and western blotting were employed to assess markers including PINK1, PARKIN, LC3B, p62, caspase3, and cleaved caspase3. The TUNEL assay was utilized to detect neuronal apoptosis, while transmission electron microscopy (TEM) was used to examine mitochondrial autophagosomes. Primary hippocampal neurons were cultured, treated, and then analyzed through immunofluorescence for mtDNA, mtROS, TMRM. Results In comparison to the control group, mitophagy levels in the experimental group were not significantly altered, yet there was a notable increase in apoptotic neurons. Furthermore, markers indicative of mitochondrial leakage and damage were found to be elevated in the experimental group compared to the control group, but these markers showed improvement following ART treatment. ART was effective in activating the PINK1/PARKIN pathway, enhancing mitophagy, and diminishing neuronal apoptosis. Behavioral assessments revealed that ART ameliorated symptoms in mice with anti-NMDAR encephalitis in the passive transfer model (PTM). The knockdown of PINK1 led to a reduction in mitophagy levels, and subsequent ART intervention did not alleviate symptoms in the anti-NMDAR encephalitis PTM mice, indicating that ART’s therapeutic efficacy is mediated through the activation of the PINK1/PARKIN pathway. Conclusions At the onset of anti-NMDAR encephalitis, mitochondrial damage is observed; however, this damage is mitigated by the activation of mitophagy via the PINK1/PARKIN pathway. This regulatory feedback mechanism facilitates the removal of damaged mitochondria, prevents neuronal apoptosis, and consequently safeguards neural tissue. ART activates the PINK1/PARKIN pathway to enhance mitophagy, thereby exerting neuroprotective effects and may achieve therapeutic goals in treating anti-NMDAR encephalitis.

IntroductionGenetic predisposition to autoimmune encephalitis with antibodies against N-methyl-D-aspartate receptor (NMDAR) is poorly understood. Given the diversity of associated environmental factors (tumors, infections), we hypothesized that human leukocyte antigen (HLA) and killer-cell immunoglobulin-like receptors (KIR), two extremely polymorphic gene complexes key to the immune system, might be relevant for the genetic predisposition to anti-NMDAR encephalitis. Notably, KIR are chiefly expressed by Natural Killer (NK) cells, recognize distinct HLA class I allotypes and play a major role in anti-tumor and anti-infection responses.MethodsWe conducted a Genome Wide Association Study (GWAS) with subsequent control-matching using Principal Component Analysis (PCA) and HLA imputation, in a multi-ethnic cohort of anti-NMDAR encephalitis (n=479); KIR and HLA were further sequenced in a large subsample (n=323). PCA-controlled logistic regression was then conducted for carrier frequencies (HLA and KIR) and copy number variation (KIR). HLA-KIR interaction associations were also modeled. Additionally, single cell sequencing was conducted in peripheral blood mononuclear cells from 16 cases and 16 controls, NK cells were sorted and phenotyped.ResultsAnti-NMDAR encephalitis showed a weak HLA association with DRB1*01:01~DQA1*01:01~DQB1*05:01 (OR=1.57, 1.51, 1.45; respectively), and DRB1*11:01 (OR=1.60); these effects were stronger in European descendants and in patients without an underlying ovarian teratoma. More interestingly, we found increased copy number variation of KIR2DL5B (OR=1.72), principally due to an overrepresentation of KIR2DL5B*00201. Further, we identified two allele associations in framework genes, KIR2DL4*00103 (25.4% vs. 12.5% in controls, OR=1.98) and KIR3DL3*00302 (5.3% vs. 1.3%, OR=4.44). Notably, the ligands of these KIR2DL4 and KIR3DL3, respectively, HLA-G and HHLA2, are known to act as immune checkpoint with immunosuppressive functions. However, we did not find differences in specific KIR-HLA ligand interactions or HLA-G polymorphisms between cases and controls. Similarly, gene expression of CD56dim or CD56bright NK cells did not differ between cases and controls.DiscussionOur observations for the first time suggest that the HLA-KIR axis might be involved in anti-NMDAR encephalitis. While the genetic risk conferred by the identified polymorphisms appears small, a role of this axis in the pathophysiology of this disease appears highly plausible and should be analyzed in future studies.

We described a challenging case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in a young girl. Despite enduring months of reduced consciousness with ongoing antibody presence, she ultimately exhibited remarkable improvement within a 5-year follow-up period. Additionally, we conducted a concise review of relevant literature on anti-NMDAR encephalitis, with a specific focus on anti-NMDAR antibodies. Our findings enhance the clinical comprehension of anti-NMDAR encephalitis and offer valuable insights to clinicians for its management.

Objective: In adult anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis, corticosteroids are commonly used as first‐line treatment. However, the optimal oral prednisone tapering (OPT) following intravenous methylprednisolone pulse therapy remains unclear. We aim to compare the efficacy and safety of different OPT courses in anti‐NMDAR encephalitis. Methods: The CHASE study, a multicenter prospective observational cohort study, enrolled patients with autoimmune encephalitis from October 2011 to March 2023. Patients were grouped based on oral prednisone tapering course: ≤3 months (Group ≤3 month), 3–6 months (Group 3–6 months, including 3 months), and >6 months (Group > 6 months). Kaplan–Meier plots were used to analyze time to relapse and time to total recovery within 2 years. Results: Among 666 screened patients, 171 (median [IQR] age 27 [21.0–36.5] years, 55.0% female) met selection criteria. Responders at 3 months were prevalent in Group ≤3 months (OR 7.251 [95% CI 2.252 to 23.344] and Group 3–6 months (OR, 3.857 [95% CI 1.107 to 13.440] than in Group >6 months. Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores at 12 months were higher in Group >6 months than in Group ≤3 months and Group 3–6 months (β, −2.329 [95% CI −3.784 to −.875]; β, −2.871 [95% CI −4.490, −1.253]). CASE seizures subscore was higher in Group >6 months than in Group 3–6 months (β, −.452 [95% CI −.788 to −.116]). No significant difference in seizure freedom rates among the groups. Adverse events were higher in Group 3–6 months and Group >6 months than in Group ≤3 months (OR 6.045 [95% CI 2.352 to 15.538]; OR 6.782 [95% CI 1.911 to 24.073]). Significance: Longer oral prednisone courses for adult patients with anti‐NMDAR encephalitis did not show superior effects compared to shorter courses in improving modified Rankin Scale (mRS) scores and CASE scores, reducing the risk of relapse within 2 years, or achieving seizure freedom. Instead, extended prednisone courses may lead to more side effects— particularly weight gain. This outcome recommends evaluating the possibility of shortening the duration of oral prednisone after a thorough patient assessment. [ABSTRACT FROM AUTHOR]

A rare autoimmune disease called anti-NMDAR encephalitis usually affects young people and frequently manifests as cognitive deterioration, seizures, and psychiatric symptoms. The diagnostic challenge and the importance in recognizing the clinical features and employing appropriate laboratory and imaging techniques for accurate and timely diagnosis will be discussed. We describe the example of an 8-year-old girl who suddenly began exhibiting strange behavioral and speech problems. Anti-NMDAR encephalitis was diagnosed after further investigation. This casee illustrates how different clinical presentations can lead to a delay in the disorder's diagnosis. Healthcare practitioners continue to have difficulties in diagnosing heterogeneous clinical manifestations of anti-NMDAR encephalitis, particularly in the juvenile age range. [ABSTRACT FROM AUTHOR]

Background: Combined first-line therapies have been frequently adopted for patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Plasma exchange (PE) or immunoadsorption (IA) was used as an add-on option following initial immunotherapies, including high-dose steroids and intravenous immunoglobulin (IVIG). However, whether a shorter delay of PE or IA can improve the early recovery prognosis of patients with anti-NMDAR encephalitis remains largely unknown. Objective: To compare short-term clinical improvement between patients with early and late initiation of PE or IA in anti-NMDAR encephalitis. Design: A retrospective study was conducted for patients admitted with anti-NMDAR encephalitis between January 2015 and December 2023 ( n = 29), including 21 patients who received PE or IA as synergistic therapies. Methods: The clinical prognosis was compared between the early PE/IA group and the late PE/IA group in the research. Primary outcome included changes in the Clinical Assessment Scale for Autoimmune Encephalitis (∆CASE) at 90 and 120 days after encephalitis onset. Secondary outcomes included changes in the modified Rankin scale (∆mRS) after 90 and 120 days from encephalitis onset, and the length of intensive care unit (ICU) stay for patients with severe anti-NMDAR encephalitis. Results: The ∆CASE scores after 90 and 120 days from encephalitis onset revealed a significant difference between patients with early and late initiation of PE or IA ( p ⩽ 0.05). A significant difference in the ∆mRS was also found between patients with early and late initiation of PE or IA in severe encephalitis ( p ⩽ 0.05). No significant difference was found in the length of ICU admission ( p = 0.101). Conclusion: Our findings emphasize the importance of considering PE or IA as early as feasible for patients with anti-NMDAR encephalitis, even when steroids and IVIG are in use.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an antibody-related autoimmune encephalitis. It is characterized by the existence of antibodies against NMDAR, mainly against the GluN1 subunit, in cerebrospinal fluid (CSF). Recent research suggests that anti-NMDAR antibodies may reduce NMDAR levels in this disorder, compromising synaptic activity in the hippocampus. Although anti-NMDAR antibodies are used as diagnostic indicators, the origin of antibodies in the central nervous system (CNS) is unclear. The blood–brain barrier (BBB), which separates the brain from the peripheral circulatory system, is crucial for antibodies and immune cells to enter or exit the CNS. The findings of cytokines in this disorder support the involvement of the BBB. Here, we aim to review the function of NMDARs and the relationship between anti-NMDAR antibodies and anti-NMDAR encephalitis. We summarize the present knowledge of the composition of the BBB, especially by emphasizing the role of BBB components. Finally, we further provide a discussion on the impact of BBB dysfunction in anti-NMDAR encephalitis.

Abstract Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most prevalent autoimmune encephalitis and is closely related to catatonia. This study aimed to investigate the clinical features and disease outcomes of adult catatonic anti-NMDAR encephalitis patients. Methods Adult patients diagnosed with anti-NMDAR encephalitis between January 2013 and October 2021 were retrospectively enrolled in this study. According to the Bush Francis Catatonia screening instrument (BFCSI), patients were divided into two groups: those with catatonia and those without catatonia. The modified Rankin scale (mRS), Clinical Assessment Scale for Autoimmune Encephalitis (CASE), Neuropsychiatric Inventory (NPI), Patient Health Questionnaire-9 (PHQ-9) and 7-item Generalized Anxiety Disorder Questionnaire (GAD-7) scores were assessed at follow-up. The Mann–Whitney U test (nonparametric), Student’s t test (parametric), and chi-squared test were used to analyse the differences between the two groups. Results Eighty-four patients were recruited, including twenty-five catatonic patients and fifty-nine noncatatonic patients. Among them, 28 had positive antibody only in cerebrospinal fluid (CSF), 4 had positive antibody only in serum and 52 had positive antibody both in CSF and serum. Catatonic patients experienced more disturbance of consciousness (p = 0.01), aggression (p = 0.046) and affective disorders (p = 0.043) than noncatatonic patients. The mRS scores of the catatonia group assessed at admission (p = 0.045) were worse than those of the non-catatonia group. Catatonic patients were more inclined to develop deep vein thrombosis (p = 0.003), decubitus (p = 0.046), pneumonia (p = 0.025), and to be admitted to the intensive care unit (ICU) (p = 0.011) than noncatatonic patients. All patients in the catatonia group received first-line immunotherapy. At the 24-month follow-up, 2 patients in the catatonia group did not achieve good outcomes. At the last follow-up, the catatonia group had more relapses (p = 0.014) and more neuropsychiatric problems (p = 0.035). Conclusions Adult anti-NMDAR encephalitis patients with catatonia present distinct clinical features in disease course and are prone to experience more relapses and long-term neuropsychiatric problems than those without catatonia.

Ofatumumab (OFA) is an anti-CD20 antibody. We assessed the therapeutic potential of OFA in five pediatric anti-NMDAR encephalitis patients who showed poor responses to the first-line immunotherapy. OFA treatment showed clinical improvement including alleviation of clinical symptoms and mRS decrease accompanied by anti-NMDAR antibody turning negative in 3 patients and decline in 2 patients. And all patients achieved B cell depletion after OFA treatment. During follow-up, all patients' symptoms were stable. OFA treatment is safe and effective, easy to administer, and favorable for pediatric anti-NMDAE encephalitis patients who are refractory to the first-line immunotherapy., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xiaojing Li reports financial support was provided by Guangzhou Municipal Science and Technology Basic and Applied Research Project. Wenlin Wu reports financial support was provided by Applied Basic Research Foundation of Guangzhou City. Chi Hou reports financial support was provided by Guangzhou Municipal Science and Technology Basic and Applied Research Project. If there are other authors, they 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. Published by Elsevier Ltd.)

Background: Combined first-line therapies have been frequently adopted for patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Plasma exchange (PE) or immunoadsorption (IA) was used as an add-on option following initial immunotherapies, including high-dose steroids and intravenous immunoglobulin (IVIG). However, whether a shorter delay of PE or IA can improve the early recovery prognosis of patients with anti-NMDAR encephalitis remains largely unknown., Objective: To compare short-term clinical improvement between patients with early and late initiation of PE or IA in anti-NMDAR encephalitis., Design: A retrospective study was conducted for patients admitted with anti-NMDAR encephalitis between January 2015 and December 2023 ( n  = 29), including 21 patients who received PE or IA as synergistic therapies., Methods: The clinical prognosis was compared between the early PE/IA group and the late PE/IA group in the research. Primary outcome included changes in the Clinical Assessment Scale for Autoimmune Encephalitis (∆CASE) at 90 and 120 days after encephalitis onset. Secondary outcomes included changes in the modified Rankin scale (∆mRS) after 90 and 120 days from encephalitis onset, and the length of intensive care unit (ICU) stay for patients with severe anti-NMDAR encephalitis., Results: The ∆CASE scores after 90 and 120 days from encephalitis onset revealed a significant difference between patients with early and late initiation of PE or IA ( p  ⩽ 0.05). A significant difference in the ∆mRS was also found between patients with early and late initiation of PE or IA in severe encephalitis ( p  ⩽ 0.05). No significant difference was found in the length of ICU admission ( p  = 0.101)., Conclusion: Our findings emphasize the importance of considering PE or IA as early as feasible for patients with anti-NMDAR encephalitis, even when steroids and IVIG are in use., (© The Author(s), 2024.)

Background: Encephalitis associated with antibodies against the N -methyl- D -aspartate receptor (NMDAR) results in a distinctive neuro-psychiatric syndrome. It has been reported that the serum phenylalanine-tyrosine (Phe/Tyr) ratio increases during infection. However, the connection between phenylalanine-tyrosine metabolism and psychiatric symptoms remains unclear., Methods: We enrolled 24 individuals with anti-NMDAR encephalitis and 18 individuals with non-inflammatory neurological diseases (OND). Chromatography was used to measure serum levels of phenylalanine and tyrosine. Serum and cerebrospinal fluid (CSF) TNF- α levels were obtained from the clinical database. The modified Rankin Scale (mRS) score and Glasgow Coma Scale (GCS) score were recorded during the acute phase. The area under the curve (AUC) of the receiver operating characteristic curve was used to assess prediction efficacy., Results: In NMDAR patients, levels of serum Phe and the ratio of serum Phe/Tyr were higher compared to OND patients. The serum Phe/Tyr ratio was also elevated in NMDAR patients with psychiatric syndrome. Furthermore, serum Phe and Tyr levels were correlated with inflammatory indexes., Conclusion: The serum Phe/Tyr ratio is elevated in NMDAR patients with psychiatric syndrome and is associated with severity. Therefore, the serum Phe/Tyr ratio may serve as a potential prognostic biomarker., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ma, Zheng, Sun, Wang, Cong, Wei, Ma, Feng, Yin and Zhang.)

Abstract Background In recent years, there have been an increasing number of reports on overlapping antibodies in autoimmune encephalitis (AE). There are various types of overlapping antibodies, but the clinical significance of each type is not yet clear. Glial antibodies, such as MOG, AQP4, and especially NMDAR, can be detected in patients with AE. However, little is known about the overlapping antibodies of anti-glial fibrillary acidic protein (GFAP), and only a few case reports have described this overlap. Case presentation The patient was a 7-year-old girl with recurrent intermittent fever and seizures, and viral encephalitis was diagnosed at the beginning of the disease. She was discharged after treatment with acyclovir, high-dose immunoglobulins, and valproic acid as an antiseizure medication. Subsequently, the patient still had occasional seizures and abnormal behavior, and the anti-NMDAR antibody test was positive (1:3.2). She was treated with high-dose methylprednisolone and antiseizure therapy. Approximately half a year later, the patient experienced fever and seizures again, serum GFAP IgG was 1:100, and a head MRI indicated new lesions. Improvement was achieved after repeated high-dose methylprednisolone and continuous prednisone anti-inflammatory therapy. Conclusions Anti-NMDAR encephalitis combined with GFAP-IgG is uncommon, and repeated tests for AE-associated antibodies may be required in patients with recurrent encephalitis. Compared with cerebrospinal fluid antibody-positive children, serum GFAP IgG-positive children should be comprehensively diagnosed according to their clinical manifestations. It is worth considering whether overlapping antibody syndrome can still be an issue for patients with AE who recover and have negative antibodies after a few months if disease recurrence and new antibodies are detected.

Introduction Anti-NMDAR encephalitis is an autoimmune disorder, characterized by neuropsychiatric symptoms, such as mood instability, psychosis, catatonia, dyskinesia, seizures and vegetative lability. Psychiatric symptoms usually occur in the initial phase, therefore almost half of the patients are first observed at a psychiatric unit, however in later phases the patients’ condition often show progression with the characteristic neurological symptoms, such as perioral dyskinesia and seizures. Although, early recognition and treatment is essential to reach good outcomes, delay in the diagnostic process often happens due to the unspecific early symptoms and the lack of knowledge of this disorder amongst psychiatrists. Moreover, there are cases, where neurological symptoms do not appear, which can lead to diagnostic failure and mismanagement of these patients. Since anti-NMDAR encephalitis is a rare condition, it is important to treat such cases in specific centres, where sufficient knowledge and multidisciplinary approaches are available. Objectives Our aim was to gather all patients’ data treated with anti-NMDAR encephalitis at two departments (Neurology and Psychiatry) of Semmelweis University. We wanted to analyse psychiatric manifestations of the disorder in details and follow these symptoms long term, with special interest on the cognitive symptoms. One of our aims was to follow-up these patients and measure antibody titres in their serum, to be able to asses, whether there was any association between prolonged serum positivity and cognitive impairment. Methods We have retrospectively analysed data of previous cases and prospectively followed up recently hospitalised patients. Neurocognitive assessment had been conducted by the same psychologist, all the patients were followed up by the same interdisciplinary team, including a neurologist and two psychiatrists. Laboratory tests (autoimmune antibody essays) were conducted by the Immunological Laboratory at Semmelweis University. Results Altogether, 13 female patients were treated with anti-NMDAR encephalitis in the past ten years at Semmelweis University. All of them received plasma exchange, iv. steroids and azathioprine. 8 out of the 13 needed ventilation and intensive care treatment. 2 of these patients have mild psychiatric symptoms as residual symptoms, and 1 of them is still in the recovery stage, currently experiencing mild cognitive symptoms. Only two patient had ovarian teratomas out of the 13, which is a lower number than expected from previous studies. 4 out of 12 had positive antibody titre at follow up, one patient is still at recovery stage, however her antibody titres are still very high. Conclusions Semmelweis University is one of the largest centre treating patients with anti-NMDAR encephalitis in Hungary. We had altogether 13 patients in the last ten years, with very good outcome, since all of them recovered, although 2 have residual symptoms. Disclosure of Interest None Declared

Rationale: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis characterized by diverse neurological and psychiatric symptoms. It predominantly affects young women, particularly those with ovarian teratomas. However, cases without teratomas are also commonly reported, often exhibiting poorer treatment responses and higher relapse rates. Persistent fever and signs of meningitis are rare in such cases. Diagnosis is confirmed through the detection of anti-NMDAR antibodies., Patient Concerns: A 15-year-old female presented with episodic loss of consciousness, fever, nuchal rigidity, limb convulsions, and psychiatric symptoms following a stressful exam period. Initial symptomatic treatments were ineffective., Diagnosis: The diagnosis of anti-NMDAR encephalitis was confirmed through lumbar puncture, brain imaging, and the detection of anti-NMDAR antibodies in cerebrospinal fluid and serum., Interventions: The patient received tailored first-line therapy, including high-dose methylprednisolone and 3 courses of intravenous immunoglobulin (IVIG)., Outcomes: The patient exhibited significant clinical improvement, with a reduction in seizure frequency and eventual complete seizure control. Body temperature normalized, and follow-up showed progressive recovery in cognitive and motor functions., Lessons: This case highlights the importance of early diagnosis and individualized treatment in anti-NMDAR encephalitis. Repeated IVIG courses proved effective, underscoring the need for personalized treatment plans in managing this condition. Persistent fever and signs of meningitis were rare and contributed to the diagnostic challenge, highlighting the clinical complexity of this case., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The clinical manifestations of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis may be closely related to the integrity of the blood-brain barrier (BBB). The P38 mitogen-activated protein kinase (P38MAPK) pathway plays a protective role in neurodegenerative diseases. However, whether the P38MAPK pathway is involved in the underlying mechanism of tight junction (TJ) protein disruption and neuronal damage has not been elucidated. Therefore, in this study, a mouse model of anti-NMDAR encephalitis was established by active immunization with NMDAR NR1 356-385 peptides. The critical pathways of P38MAPK were screened by interaction network and co-enrichment analysis. The role of P38MAPK pathways was investigated by the injection of P38MAPK inhibitor SB203580 (10 mg/kg, i.p.). Compared with the control group, the expression of occludin and zonula occludens (ZO)-1 in NMDAR NR1 356-385 group mice was downregulated, and the structure and function of BBB were damaged. However, after the intervention of SB203580, the activation of the P38MAPK was inhibited, the expression of matrix metalloproteinase 9 (MMP9) was reduced, and the function of BBB was improved. Meanwhile, inhibiting the P38MAPK pathway reversed the degradation of NMDAR NR1, while reducing the expression of the glial fibrillary acidic protein (GFAP) and pro-inflammatory factor tumor necrosis factor (TNF-α). It also relieved the damage of neuron-specific nucleus (NeuN), thus alleviating psychobehavioral symptoms. In conclusion, our results suggested that the P38MAPK pathway is involved in BBB destruction and neurobehavioral change in mice with anti-NMDAR encephalitis. Targeting the P38MAPK pathway may be a promising option for the treatment of anti-NMDAR encephalitis., Competing Interests: Declarations Conflict of interest The authors report there are no competing interests to declare. Ethical Approval Animal experiments in this study have been approved by the Animal Experimentation Ethics Committee of Guangxi Medical University (Certificate Numbers: 202010031). The experiments were performed and reported in accordance with the ARRIVE guideline., (© 2024. The Author(s).)

Rituximab is recommended as the preferred second-line immunotherapy for autoimmune encephalitis (AE). However, Ofatumumab (OFA), a novel fully human anti-CD20 antibody, has been reported infrequently in patients with AE. Among the various forms of AE, anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is the most common and severe. This study presents three cases of severe anti-NMDAR encephalitis treated with OFA following the failure of first-line immunotherapy. The results indicated that the patients experienced no significant adverse reactions after receiving OFA, and their clinical symptoms improved markedly within one week of treatment. One month post-treatment with OFA, scores on the Glasgow Coma Scale (GCS) and the Barthel Index of Activities of Daily Living (Barthel-ADL) increased, while scores on the modified Rankin Scale (mRS), Clinical Assessment Scale in Autoimmune Encephalitis (CASE), and Paroxysmal Sympathetic Hyperactivity Assessment Measure (PSH-AM) decreased. During the three-month and six-month follow-up periods, patients exhibited further symptomatic improvement, suggesting that OFA is a safe and effective treatment option for anti-NMDAR encephalitis. These findings propose a novel therapeutic strategy for severe refractory anti-NMDAR encephalitis., Competing Interests: Declaration of competing interest There are no potential conflicts of interest regarding the study, authorship and publication of this article., (Copyright © 2024. Published by Elsevier B.V.)

Background: Anti-NMDA receptor (A-NMDAR) encephalitis is an autoimmune condition often associated with ovarian teratoma. Surgical removal of the teratoma is generally curative, and recurrence is uncommon. Case: A 14-year-old female presented with psychiatric symptoms and was ultimately diagnosed with A-NMDAR encephalitis during a prolonged hospitalization. She was found to have bilateral ovarian teratomas, underwent laparoscopic bilateral ovarian cystectomy, and returned to neurologic baseline within 2 months. One year later, the patient was re-presented with similar symptoms and was diagnosed with recurrent A-NMDAR encephalitis. Initial imaging was negative for ovarian teratomas. After another prolonged hospitalization, repeat imaging ultimately demonstrated a suspected left ovarian teratoma. A left salpingo-oophorectomy was performed, and the patient's condition again fully recovered. Conclusion: This case of A-NMDAR encephalitis presented with many atypical features including neuropsychiatric presenting symptoms, bilateral teratomas, and severe recurrence of disease. While imaging is the recommended modality for investigation of etiology, no teratoma was identified on the second presentation, leading to an ethical and clinical conundrum in this adolescent patient. More research is needed to investigate other diagnostic methods for A-NMDAR encephalitis without distinct teratoma on imaging in female patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Shadowen Caroline et al.)

Sleep disorders have been described in anti-NMDAr encephalitis including insomnia, hypersomnia, narcolepsy, and sleep-disordered breathing. A patient presented with typical features of anti-NMDAr encephalitis associated with a right ovarian teratoma. After two months of clinical improvement with immunotherapy, the patient deteriorated. A 24-hour video EEG-polysomnography revealed a severe sleep quantity deficit, a total destruction of sleep architecture consisting of short clusters of N1 and rapid eye movement sleep stages, associated with motor and autonomic hyperactivity. These features were consistent with agrypnia excitata and were associated with disease reactivation due to a left ovarian teratoma. A new course of immunotherapy and surgery improved clinical symptoms and normalized sleep patterns. Agrypnia excitata, the most severe form of status dissociatus , was a sleep biomarker of disease relapse in this patient. Polysomnographic studies in the acute phase of anti-NMDAr encephalitis are lacking and are needed to better understand the evolution of sleep patterns., (© 2024 American Academy of Sleep Medicine.)

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disease of the central nervous system with unknown etiology and multiple triggers. It is clinically characterized by the onset of psychiatric symptoms, seizures, memory disturbance, and cognitive decline. We present a young, newly married woman in the first trimester of pregnancy who presented with purely psychiatric manifestations, fever, and two instances of generalized tonic-clonic seizures. She eventually progressed to develop a decreased level of consciousness and hemodynamic instability. A diagnosis was made of anti-NMDA encephalitis. Her symptoms progressed even after the administration of two intravenous immunoglobulin (IVIG) trials, steroids, and three anti-seizure medications until she experienced a spontaneous abortion. She then gradually returned to her normal baseline condition. This case underscores the importance of suspecting anti-NMDAR encephalitis in pregnant patients with acute onset of psychiatric manifestations. Anti-NMDAR encephalitis can be a difficult, challenging, and exhausting diagnosis for both the patient and treating physicians, particularly in pregnant patients where diagnostic and therapeutic options may be limited due to concerns for fetal safety. However, this case provides evidence that anti-NMDAR encephalitis during pregnancy can have a good prognosis., 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, Almalki et al.)

BackgroundAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a recently discovered autoimmune syndrome associated with psychosis, dyskinesia, and seizures. However, the underlying mechanisms of this disease remain unclear, in part because of a lack of suitable animal models.MethodsThis study describes a novel female C57BL/6 mouse model of anti-NMDAR encephalitis that was induced by active immunization against NMDARs using an amino terminal domain (ATD) peptide from the GluN1 subunit (GluN1356-385).ResultsTwelve weeks after immunization, the immunized mice showed significant memory loss. Furthermore, antibodies from the cerebrospinal fluid of immunized mice decreased the surface NMDAR cluster density in hippocampal neurons which was similar to the effect induced by the anti-NMDAR encephalitis patients' antibodies. Immunization also impaired long-term potentiation at Schaffer collateral-CA1 synapses and reduced NMDAR-induced calcium influx.ConclusionWe established a novel anti-NMDAR encephalitis model using active immunization with peptide GluN1356-385 targeting the ATD of GluN1. This novel model may allow further research into the pathogenesis of anti-NMDAR encephalitis and aid in the development of new therapies for this disease.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune-mediated disease characterized by complicated neuropsychiatric symptoms and the detection of cerebrospinal fluid antibodies against the GluN1 subunit of the NMDAR. With the proposed clinical method, more anti-NMDAR encephalitis patients have been discovered since its first report. However, anti-NMDAR encephalitis overlapping with multiple sclerosis (MS) is rare. Herein we report a male patient with anti-NMDAR encephalitis who developed MS in mainland China. Furthermore, we summarized the characteristics of patients who were diagnosed with overlapping MS and anti-NMDAR encephalitis in previous studies. Additionally, we pioneered the use of mycophenolate mofetil in immunosuppressive therapy, providing a novel therapeutic alternative for overlapping anti-NMDAR encephalitis and MS.