Search

Rationale: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a rare disease and common type of autoimmune encephalitis. The prognosis of patients with comorbid disorders of consciousness is poor, and no such acupuncture treatment has been reported. We report a case of acupuncture in anti-NMDAR encephalitis with a high cerebrospinal fluid titer combined with impaired consciousness., Patient Concerns: A 13-year-old girl with anti-NMDAR encephalitis presented to our hospital with impaired consciousness., Diagnoses: Therefore, the patient was diagnosed with anti-NMDAR encephalitis. According to the Chinese medicine theory, the diagnosis was Shenhun(phlegm obstructs the clear orifices)., Interventions: Depending on the patient's condition, we used the Xingnao Kaiqiao acupuncture therapeutic method., Outcomes: After 16 weeks of acupuncture treatment, the patient awoke and resumed a normal life with no recurrence at one-year follow-up., Conclusion: This case demonstrated that acupuncture can be used as a complementary and alternative treatment for anti-NMDAR encephalitis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a rare autoimmune neurologic disorder, the genetic etiology of which remains poorly understood. Our study aims to investigate the genetic basis of this disease in the Chinese Han population., Methods: We performed a genome-wide association study and fine-mapping study within the major histocompatibility complex (MHC) region of 413 Chinese patients with anti-NMDAR encephalitis recruited from 6 large tertiary hospitals and 7,127 healthy controls., Results: Our genome-wide association analysis identified a strong association at the IFIH1 locus on chromosome 2q24.2 (rs3747517, p = 1.06 × 10 -8 , OR = 1.55, 95% CI, 1.34-1.80), outside of the human leukocyte antigen (HLA) region. Furthermore, through a fine-mapping study of the MHC region, we discovered associations for 3 specific HLA class I and II alleles. Notably, HLA-DQB1*05:02 ( p = 1.43 × 10 -12 ; OR, 2.10; 95% CI 1.70-2.59) demonstrates the strongest association among classical HLA alleles, closely followed by HLA-A*11:01 ( p = 4.36 × 10 -7 ; OR, 1.52; 95% CI 1.29-1.79) and HLA-A*02:07 ( p = 1.28 × 10 -8 ; OR, 1.87; 95% CI 1.50-2.31). In addition, we uncovered 2 main HLA amino acid variation associated with anti-NMDAR encephalitis including HLA-DQβ1-126H ( p = 1.43 × 10 -12 ; OR, 2.10; 95% CI 1.70-2.59), exhibiting a predisposing effect, and HLA-B-97R ( p = 3.40 × 10 -8 ; OR, 0.63; 95% CI 0.53-0.74), conferring a protective effect. Computational docking analysis suggested a close relationship between the NR1 subunit of NMDAR and DQB1*05:02., Discussion: Our findings indicate that genetic variation in IFIH1, involved in the type I interferon signaling pathway and innate immunity, along with variations in the HLA class I and class II genes, has substantial implications for the susceptibility to anti-NMDAR encephalitis in the Chinese Han population.

Background: Anti-NMDA receptor encephalitis frequently presents with a wide range of psychiatric and behavioral symptoms such as catatonia and psychosis. Although immunomodulatory therapy, together with the teratoma removal whenever present, is the mainstay treatment, additional treatments are often needed to mitigate the psychosis and catatonia. However, antipsychotics are often either ineffective or poorly tolerated. We present a single-health system retroactive case series of the use of electroconvulsive therapy (ECT) in catatonic syndrome of definitive, probable, or possible immune origin. Objective: To determine the efficacy and safety of ECT for the management of catatonic syndrome associated with anti-NMDAR encephalitis and new-onset psychoses of suspected immune origin using consensus criteria described by Pollak et al in 2020. Methods: A retrospective medical records review on the demographic data, clinical characteristics, relevant laboratory findings, immunomodulatory therapies administered, and clinical outcomes of all the patients treated with ECT at our health system from Jan 2017 to Dec 2022 for the catatonic syndrome associated with anti-NMDR encephalitis or new-onset psychosis of either possible or probable immune origin. Clinical assessment of catatonic symptoms using the Bush Francis Catatonia Rating Scale (BFCRS) before and after ECT treatments as well as the time interval from the estimated onset of illness to first ECT treatment were reviewed and reported. Results;: There were 12 cases of ECT used as an adjuvant therapy to manage persistent catatonic syndrome, despite treatment with various immunotherapies, associated with either anti-NMDAR encephalitis (n=4), or new-onset psychosis of possible (n=2) or probable (n=6) immune origin. Patients were often young (mean age 26 years) with slight female predominance (58%). Mean initial BFCRS score was 18.2 (range: 5-25). All patients responded well to the combination of immunotherapies and ECT, and showed some response after 3 ECT treatments. Complete resolution of catatonia was achieved in 11 patients (92%). Patients required an average of 11 ECT treatments (range: 3-21) to achieve maximum improvement. Conclusions: This is the largest single-health system retrospective case series showing ECT modality to be highly effective and safe adjuvant therapy for all forms of catatonic syndrome of confirmed or suspected immune origin, including those refractory to the standard treatment combined with immunotherapies. Our report underscores the importance of high index of clinical suspicion in early recognition of the immune-mediated catatonic syndrome, particularly among those with a prior history of psychiatric illnesses. This is important to prevent catatonia-related medical complications. It also provides additional support for early and consistent use of ECT modality in the management of immune-mediated catatonia in association with anti-NMDAR encephalitis and other suspected central nervous system autoimmunity. Large-scale randomized clinical studies might provide pivotal insights sufficient for incorporating ECT modality into the treatment algorithm for catatonic syndrome associated with autoimmunity.

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.

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.

Nosocomial infections during immunotherapy pose a dilemma in the treatment of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, where a lack of consensus guidelines for this rare disease marks a significant gap in the existing knowledge. This case reports about an 18-year-old female diagnosed with anti-NMDAR encephalitis who was found to be refractory to first- and second-line treatment. During her hospital stay, the patient encountered nearly six episodes of infection, which delayed the use of next-line intervention. It was observed that switching over to the next line of treatment during infections may produce sub-therapeutic outcomes. Thereby, the case highlights the need for de-escalation and appropriate selection of immunosuppression therapy during nosocomial infections and how monotherapy with the patient-tolerated first-line agent can be appropriate during infection.

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.

Abstract Background Approximately half (55%) of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is known to show abnormal brain images, including high signal intensity in T2 or fluid attenuated inversion recovery (FLAIR) images. In a minority of anti-NMDAR encephalitis cases, high signal intensity on diffusion-weighted imaging (DWI) has been reported, a finding that is highly suggestive of a stroke. Case presentation We present the case of a 66-year-old man who experienced two separate focal seizure events, which involved first the right and then the left upper extremity in a short period of time. The patient showed focal clonic seizures involving right arm and hand, which sometimes evolved to bilateral tonic-clonic seizures on his first admission. Brain magnetic resonance imaging (MRI) showed high signal intensity on DWI and low signal intensity on the apparent diffusion coefficient (ADC) map of the left caudate nucleus and putamen. The patient was discharged symptom-free with anti-epileptic drugs for 2 weeks. The second admission occurred 4 days after the discharge. He exhibited a new symptom of focal clonic seizures involving left arm and hand while showing a brain lesion on the opposite side which is hyperintense on DWI image and hypointense on ADC map. The patient was eventually diagnosed with anti-NMDAR encephalitis according to the cerebrospinal fluid (CSF) antibody test. Conclusions This is the case of anti-NMDAR encephalitis patient whose DWI/ADC images revealed sequential involvement on the left and right basal ganglia with a short time interval. When stroke-like brain lesions on DWI are found in a patient with a focal seizure, a CSF study could help rule out autoimmune encephalitis. We also suggest that DWI/ADC map images may be useful for the early detection of anti-NMDAR 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.

Introduction Anti NMDAR encephalitis is a relatively common autoimmune encephalitis characterized by complex neuropsychiatric features and the presence of Immunoglobulin G antibodies against the NR1 subunit of the NMDA receptors in the central nervous system. It causes psychiatric features, confusion, memory loss and seizures followed by a movement disorder, loss of consciousness and changes in blood pressure, heart rate and temperature. Postpartum depression symptoms usually develop within the first few weeks after giving birth , but may begin earlier/during pregnancy / or later /up to a year after birth. They include: inability to sleep or sleeping too much, depressed mood or severe mood swing, difficulty bonding with your baby, withdrawing from family and friends, fatigue or loss of energy, feelings of shame, guilt or inadequacy, diminished ability to think clearly, concentrate or make decisions, anxiety and panic attacks, thoughts of harming yourself or your baby. Untreated may last for many months or longer. Objectives Recent studies have highlighted the possibility that a subset of patients with first-onset severe psychiatric episodes might suffer from undiagnosed autoimmune encephalitis. The acute onset of severe atypical psychiatric symptoms in young female patients should raise the index of suspicion for anti-NMDA receptor encephalitis, particularly in the setting of neurological symptoms, including side effects of antipsychotic treatment. Methods / Results / Conclusions Creating a therapeutic environment is an interdisciplinary clinical and theoretical approach to psychiatric treatment in hospital settings, the basic idea of which is that the entire environment has therapeutic potential. Psychodinamic knowledge and understanding of the process as well as principles of body-oriented psychotherapy may be of great importance in the treatment of these patients in addition to the use of pharmacotherapy. Disclosure of Interest None Declared

Background and Objectives: A clinical practice guideline (CPG) was created to standardize evaluation and treatment for patients with suspected anti-methyl-d-aspartate receptor (NMDAR) autoimmune encephalitis (AE), the most common AE in children. The objective of this study was to evaluate the CPG effect on time to diagnosis, treatment, and hospital length of stay (LOS)., Methods: Patients with an inpatient consult to pediatric rheumatology for AE during a 4-year period (period 2) after CPG implementation were identified. Data were extracted and compared with data over the preceding 4-year period (period 1)., Results: During period 1, fewer patients underwent diagnostic testing than during period 2 (34 vs 80). Number of patients diagnosed with AE did not differ from period 1 to that from period 2 (NMDAR AE 9 vs 8; seronegative AE 4 vs 5). The average time to diagnostic evaluation with lumbar puncture decreased from 5.4 to 1.5 days ( p = 0.0082), and time to treatment decreased from 7.6 to 3.9 days ( p = 0.018). LOS showed a trend toward improvement (40.4-29.2 days ( p = 0.23))., Discussion: Creation of a CPG for patients with suspected AE was associated with an improved time to diagnostic evaluation and treatment. With the CPG, more patients underwent AE testing, though total diagnoses remained the same., Competing Interests: The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp., (© 2023 American Academy of Neurology.)

Purpose: To assess the efficacy and safety of rituximab treatment as second-line immunotherapy in pediatric cases of anti-NMDA receptor (NMDAR) encephalitis.Methods: We retrospectively recruited 8 patients with anti-NMDAR encephalitis who were treated with rituximab as second-line immunotherapy. We evaluated the clinical features, laboratory examination results and treatment protocols of the Chinese children and defined good outcomes based on the modified Rankin scale (mRS) score (0–2) at the last follow-up.Results: A total of eight pediatric patients (median age 6.7 years; four female) with refractory anti-NMDAR encephalitis were recruited to the study. Rituximab was given after a median duration of disease of 57 days (range 50.5–113.75 days). The use of rituximab led to a significant reduction in the mRS and CD19+ B-cells compared to before rituximab infusion (P < 0.05). Five patients (62.5%) had a good outcome (mRS ≤ 2) including four patients (50%) who showed complete recovery (mRS = 0) at the last follow-up. Transient infusion adverse events were recorded in 2 patients (25%). Two patients (25%) had severe infectious adverse events (AEs) and two patients with grade 5 (death). None of the patients developed progressive multifocal leukoencephalopathy (PML).Conclusion: Our study provides evidence that rituximab can efficiently improve the clinical symptoms of anti-NMDAR encephalitis in children. However, due to the risk of adverse infections, rituximab should be restricted in pediatric patients with high rates of mortality and disability.

Infliximab, a chimeric monoclonal antibody against anti-tumor necrosis factor-α (TNF-α), has revolutionized the management of inflammatory bowel disease. However, a recent nested case-control study showed that anti-TNF-α therapy exposure in patients with autoimmune diseases is associated with an increased risk of inflammatory central nervous system (CNS) events. A 27-year-old man diagnosed with Crohn’s disease at 17 years of age was referred to our clinic for suffering with Wernicke’s aphasia and the right-hand weakness over two weeks. Nine years of treatment for Crohn’s disease with infliximab anti-TNF-α therapy was well tolerated. An initial MRI revealed diffuse leptomeningeal enhancement along the bilateral cerebral sulci without any parenchymal abnormalities. Cerebrospinal fluid (CSF) and serum N-methyl-D-aspartate receptor (NMDAR) antibody testing yielded positive results. Anti-NMDAR encephalitis was diagnosed, and the patient was treated with rituximab. A follow-up brain MRI showed new multiple cerebral lesions in the left insular cortex and subcortical white matter of the left frontal and temporal gyri. Approximately 8 months after symptom onset, the CSF and serum NMDAR antibody converted to negative. Twelve months later, the patient fully recovered from anti-NMDAR encephalitis without any neurological deficits and is currently being treated with the anti-interleukin 12/23 agent ustekinumab for Crohn’s disease. This is the first report of not only a patient with infliximab-associated anti-NMDAR encephalitis in Crohn’s disease but also of an inflammatory non-demyelinating CNS event during long-term suppression of TNF-α. Our case highlights the need for clinicians to recognize the possibility of a paradoxical autoimmune response occurring with novel biological therapies.

PurposeSystemic autoantibodies are important for the diagnosis of autoimmune diseases, but their roles in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis are unknown. The purpose of our study is to investigate the characteristics and a prognosis of anti-NMDAR encephalitis with the prevalence of autoantibodies.MethodsSystemic autoantibodies were evaluated in 64 patients with anti-NMDAR encephalitis and 14 patients with autoimmune encephalitis with other forms. Then, according to systemic autoantibodies, patients with anti-NMDAR encephalitis were divided into an anti-nuclear antibody (ANA) positive group and an ANA negative group. The clinical outcome was assessed by a modified Rankin score at 12 months after the disease onset.ResultsA total of 64 patients with anti-NMDAR encephalitis were enrolled, of which 28.13% (18/64) were positive for ANA. The titers of a positive anti-NMDAR antibody in CSF (p = 0.041) and serum (p = 0.031) in the ANA-positive group were significantly higher than the ANA-negative group. Patients with ANA positive than those with ANA negative showed lower rates of headache (p = 0.047) and speech disorder (p = 0.049). The presence of ANA was associated with a worse clinical outcome at 12 months (p = 0.043).ConclusionANA was prevalent in patients with anti-NMDAR encephalitis, and associated with a worse prognosis and impaired neurological recovery.

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.

ObjectivesTo summarize the cytokine/chemokine levels of anti-N-methyl-Daspartate receptor encephalitis (NMDAR-E) and explore the potential role of these molecules and immune cells in the pathogenic mechanism.MethodsThe PubMed, Cochrane Library, Embase, and Web of Science databases were searched for various articles that assessed the concentrations of cytokines/chemokines in the unstimulated cerebrospinal fluid (CSF) or serum of patients with NMDAR-E in this systematic review and meta-analysis. The standardized mean difference (SMD) and 95% confidence interval (CI) were calculated by Stata17.0.ResultsA total of 19 articles were included in the systematic review from 260 candidate papers, and cytokine/chemokine levels reported in the CSF/serum were examined in each article. This meta-analysis included 17 eligible studies comprising 579 patients with NMDAR-E, 367 patients with noninflammatory neurological disorders, and 42 healthy controls from China, Spain, South Korea, Australia, Czechia, and Sweden. The results indicated that the levels of different cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, IL-13, IL-1β, IL-12, and IL-17 and chemokine C-X-C motif ligand (CXCL)10 in the CSF were significantly higher in NMDAR-E patients with a large effect size. In addition, B cell activating factor (BAFF), CXCL13, and interferon (IFN)-γ levels in the CSF were higher in NMDAR-E patients with a middle effect size. In contrast, levels of IL-2 and IL-4 in the CSF and CXCL13 and BAFF in the serum did not show a significant difference between cases and controls.ConclusionsThese analyses showed that the central immune response in NMDAR-E is a process that involves multiple immune cell interactions mediated by cytokines/chemokines, and T cells play an important role in the pathogenesis of immunity.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022342485).

Anti-N-methyl-D-aspartate receptor antibody and myelin oligodendrocyte glycoprotein antibody can coexist. Some patients have NMDAR encephalitis and MOG antibody disease successively. We report a rare case of MOGAD following anti-NMDAR encephalitis. Three years ago, a female of 44 years, our patient developed headache, mental disorder, and epilepsy. Cerebrospinal fluid was positive for NMDAR antibodies, and the patient's symptoms improved after immunomodulatory treatment. Three months ago, the patient had a sudden loss of vision in the left eye. Orbital magnetic resonance imaging was supportive of left optic neuritis. Cerebrospinal fluid was positive for NMDAR and MOG antibodies. She was then diagnosed with MOGAD with anti-NMDAR encephalitis. In conclusion, when patients with anti-NMDAR encephalitis have demyelinating symptoms such as decreased vision, numbness or weakness of the limbs, it is necessary to consider whether they are combined with MOGAD. [ABSTRACT FROM AUTHOR]

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., 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 © 2023 Gong, Wang, Zhu, Tang, Wu and Meng.)

Background: First-episode schizophrenia (FES) and anti-NMDAR encephalitis are different disorders with similar psychiatric symptoms, and both diseases are associated with the inflammatory system. In this study, we compared hematological parameters and inflammation ratios in anti-NMDAR encephalitis, FES, and healthy control.Methods: We enrolled 106 patients (53 FES patients and 53 anti-NMDAR encephalitis patients) and 59 healthy controls. The values of the neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR), and systemic immune-inflammation index (SII) were used to evaluate inflammation. Other parameters such as the white blood cell (WBC), platelet (PLT), uric acid (UA), total bilirubin (TBIL), total bile acid (TBA), and serum albumin counts were also used to compare inflammation ratios between these two diseases.Results: SII, NLR, PLR, MLR, and serum albumin levels were statistically significantly different between these three groups (p < 0.05). The values of SII, NLR, PLR, and MLR were significantly higher in the anti-NMDAR encephalitis group than those in the FES group (p < 0.05), and the values in both diseases were more increased than those in HC (p < 0.05). The serum albumin level was significantly lower in anti-NMDAR encephalitis than in FES (p < 0.05). WBC, neutrophil, lymphocyte, and monocyte counts showed significantly higher levels in the anti-NMDAR encephalitis group and FES group separately (p < 0.05). Other parameters like TBA, TBIL, and UA showed no difference between groups.Conclusion: In summary, this is a relatively new study that is innovative by comparing some inflammation markers of peripheral blood in two diseases with clinically psychotic symptoms. These two diseases are related to the inflammatory system, proving that NMDAR dysfunction is related to psychotic symptoms. Besides, NLR, PLR, MLR, and serum albumin can be used as biomarkers to distinguish the two diseases. The serum albumin level in patients with anti-NMDAR encephalitis was lower than that in patients with schizophrenia.

BackgroundCases of tuberculosis triggering the development of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis are absent.Case PresentationHerein, we report, for the first time, the case of a patient who developed anti-NMDAR encephalitis likely due to tuberculosis. The patient, a 33-year-old man, experienced weight loss during the previous 2 years, along with acute headache, fever, cognitive deficits, and right ophthalmoplegia. Based on these findings and on data from magnetic resonance imaging and cerebrospinal fluid antibody analysis, tuberculous meningoencephalitis combined with anti-NMDAR encephalitis was diagnosed. Marked clinical and brain imaging improvement were observed after antituberculosis and high-dose corticosteroid treatment initiation, which persisted during the 3 months of follow-up.ConclusionsThis case suggests that anti-NMDAR encephalitis may arise after tuberculosis infection. Therefore, clinicians must be aware of this possibility, especially when cognitive and new neurological symptoms suddenly occur.

Abstract Background Anti-NMDA receptor encephalitis is an immune-mediated disorder characterized by antibodies against the GluN1 subunit of the NMDA receptor that is increasingly recognized as a treatable cause of childhood epileptic encephalopathy. In adults, the disorder has been associated with reversible changes in brain volume over the course of treatment and recovery, but in children, little is known about its time course and associated imaging manifestations. Case presentation A previously healthy 20-month-old boy presented with first-time unprovoked seizures, dysautonomia, and dyskinesia. Paraneoplastic workup was negative, but CSF was positive for anti-NMDAR antibodies. The patient’s clinical condition waxed and waned over a 14-month course of treatment with first- and second-line immunotherapies (including steroids, IVIG, rituximab, and cyclophosphamide). Serial brain MRIs scans obtained at 5 time points spanning this same period showed no abnormal signal or enhancement but were remarkable for cycles of reversible regional cortical volume loss. All scans included identical 1-mm resolution 3D T1-weighted sequences obtained on the same 3 T scanner. Using a novel longitudinal processing stream in FreeSurfer6 (Reuter M, et. al, Neuroimage 61:1402–18, 2012) we quantified the rate of change in cortical volume at each vertex (% volume change per month) between consecutive scans and correlated these changes with the time course of the patient’s treatment and clinical response. We found regionally specific changes in cortical volume (up to 7% per month) that preferentially affected the frontal and occipital lobes and paralleled the patient’s clinical course, with clinical decline associated with volume loss and clinical improvement associated with volume gain. Conclusions Our results suggest that reversible cortical volume loss in anti-NMDA encephalitis has a regional specificity that mirrors many of the clinical symptoms associated with the disorder and tracks the dynamics of disease severity over time. This case illustrates how quantitative morphometric techniques can be applied to clinical imaging data to reveal patterns of brain change that may provide insight into disease pathophysiology. More widespread application of this approach might reveal regional and temporal patterns specific to different types of autoimmune encephalitis, providing a tool for diagnosis and a surrogate marker for monitoring treatment response.