anti-NMDAR Encephalitis Research Articles

The association between neurological symptoms and the outcomes of N-methyl-D-Aspartate receptor encephalitis treatment

Objective: To analyze the relationship between neurological symptoms and treatment outcomes of anti-NMDA receptor encephalitis at the Neurology Center of Bach Mai Hospital. Subjects: We selected 50 who were diagnosed with encephalitis at Bach Mai Hospital from January 1st, 2020, to October 31st, 2023. Methods: Cross-sectional descriptive study. Results: Among the 50 patients studied, 48% achieved good treatment outcomes, while 52% had poor outcomes. There was evidence of a significant difference in treatment outcomes between the group with symptoms such as consciousness disorders, dyskinesia and movement disorders, speech disorders, and dysautonomia compared to the group without these symptoms (p<0.05). There was no significant difference in treatment outcomes between the group with symptoms such as seizures, memory impairment, and sleep disorders compared to the group without these symptoms (p>0.05). Conclusion: In our study, 48% of patients achieved good treatment outcomes at discharge. Symptoms of consciousness disorders, dyskinesia and movement disorders, speech disorders, and dysautonomia were associated with treatment outcomes.

Rate of Autoimmune Encephalitis in Children With First-Episode Psychosis

BackgroundAutoimmune encephalitis (AE) can present as first-episode psychosis (FEP) in children. An FEP diagnostic algorithm has been proposed, but how this algorithm applies to children is unknown. We assess the FEP diagnostic algorithm in children with FEP. MethodsThe FEP algorithm was applied to a retrospective cohort of children with FEP without other neurological symptoms. ResultsTwenty-four patients were included, with five AE (anti-N-methyl-d-aspartate receptor encephalitis) and 19 non-AE patients (12 primary psychiatric, two headaches, mycoplasma-related encephalitis, post–coronavirus disease 2019 encephalitis, drug reaction with eosinophilia and systemic symptoms [DRESS] syndrome, cobalamin C deficiency, and two unknown). Some non-AE patients (five of 19 = 26%) received immunotherapies, with symptom resolution in one of five (20%) with immunotherapy and in four of 14 (29%) without immunotherapy. The FEP algorithm recommended cerebrospinal fluid (CSF) testing in all (five of five = 100%) patients with AE and in six of 19 (32%) non-AE patients, resulting in 100% sensitivity (95% confidence interval [CI]: 100% to 100%) and 45.5% specificity (95% CI: 16% to 75%), with a negative predictive value of 100% (95% CI: 100% to 100%). ConclusionsFEP can occur in children from different causes, including AE and metabolic conditions. Evaluation of FEP should be broad, especially without CSF evidence of inflammation. The FEP algorithm is useful to assess patients who would benefit from CSF testing and should be assessed in larger cohorts.

Chaihu Guizhi Decoction prevents cognitive, memory impairments and sensorimotor gating deficit induced by N-methyl-d-aspartate receptor antibody in mice

Ethnopharmacological relevanceAnti-NMDAR encephalitis is one of the most common types of autoimmune encephalitis, primarily presenting with prodromal symptoms, such as fever and headache, followed by a range of neurological and psychiatric symptoms. Chaihu Guizhi Decoction (CGD), a traditional Chinese medicine formulated by Zhang Zhongjing in the Eastern Han Dynasty, has been effectively used in clinical practice to treat the symptoms of Taiyang and Shaoyang disorders, including fever, headache, and psychiatric disorders. Aim of the studyTo demonstrate the protective effects of CGD in an animal model of anti-NMDAR encephalitis and explore the potential mechanisms involved. Materials and methodsUHPLC-HRMS was used to identify CGD's chemical components and serum metabolomic profiles. Network pharmacology and molecular docking were performed to predict potential targets of CGD for the treatment of anti-NMDAR encephalitis. The effect of CGD on anti-NMDAR encephalitis was evaluated using a mouse model induced by patients' antibodies. Behavioral tests were performed to assess cognitive impairment and schizophrenia-like behaviors. The effect of CGD on the cell-surface NMDAR GluN1 subunit in cultured neurons treated with patient antibodies was detected by immunofluorescence. Golgi staining was used to observe morphological changes in hippocampal dendrites. The expression of NMDAR-interacting proteins and various neuroreceptors in the hippocampus were examined to validate the targets predicted using network pharmacology and molecular docking. ResultsCGD alleviated cognitive, memory, and sensorimotor gating deficits in mice treated with anti-NMDAR encephalitis patients’ antibodies. Further experiments demonstrated the effect of CGD in preventing NMDAR reduction both in vitro and in vivo. Meanwhile, CGD regulated NMDAR-interacting proteins and dopamine receptors but did not affect hippocampal dendritic morphology and synaptic density. Additionally, CGD modifies metabolic pathways associated with anti-NMDAR encephalitis and other neurological and psychiatric disorders. ConclusionsCGD exhibited protective effects against anti-NMDAR encephalitis by mitigating the antibody-induced reduction in NMDAR and NMDAR-interacting proteins.

Ofatumumab treatment for severe refractory anti-NMDAR encephalitis: A case series

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.

Olanzapine vs. magnesium valproate vs. lamotrigine in anti-N-methyl-D-aspartic acid receptor encephalitis: a retrospective study

BackgroundThis study aimed to compare the impact of olanzapine, magnesium valproate, and lamotrigine as adjunctive treatments for anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. And it is expected to add supporting points related to the rebalance of neurotransmitters in the brain through adjuvant therapy in the clinical management of anti-NMDAR encephalitis.MethodsThis retrospective study included patients diagnosed with anti-NMDAR encephalitis who received standardized immunotherapy at Hunan Brain Hospital between January 2018 and December 2020.ResultsCompared to the olanzapine group, both the magnesium valproate and lamotrigine groups showed lower scores on the positive and negative symptom scale (PANSS) total score after 3 weeks of treatment (all P < 0.05). The Montreal Cognitive Assessment Scale (MoCA) scores in the magnesium valproate and lamotrigine groups were significantly higher than in the olanzapine group after 3 weeks and 3 months of treatment (all P < 0.05). After 3 months of treatment, the proportions of patients with a modified Rankin scale score (mRS) of 0–1 in the magnesium valproate and lamotrigine groups were significantly higher than in the olanzapine group (all P < 0.05). The electroencephalogram (EEG) abnormality ranks at 3 months were significantly lower in the magnesium valproate and lamotrigine groups compared with the olanzapine group (all P < 0.05). Furthermore, the Glx/Cr ratio significantly decreased after 3 months of treatment (all P < 0.05) in the magnesium valproate and lamotrigine groups, while the Glx/Cr ratio in the olanzapine group showed no significant change (P > 0.05).ConclusionCompared with olanzapine, the addition of magnesium valproate or lamotrigine to immunotherapy might be associated with a lower PANSS score, higher MoCA score, and lower mRS score. The improvement of neurological functions and cognitive function may be related to the decreased Glx/Cr ratio.

Efficacy and Safety of Rituximab Treatment for Anti-N-Methyl-d-Aspartate Receptor Encephalitis Without Tumor in Children

BackgroundTo evaluate the efficacy and safety of rituximab treatment for anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis without tumor in children. MethodsEighteen pediatric patients with NMDAR encephalitis treated with rituximab after failure of intravenous immunoglobulin (IVIG) and methylprednisolone treatment were analyzed retrospectively in terms of their medical history, clinical features, laboratory examination results, and treatments. The modified Rankin scale (mRS) score, peripheral blood CD19+ B cells, recurrence, and adverse events were used to evaluate the efficacy and safety of rituximab. ResultsThe patients were treated with rituximab 3.2 ± 1.0 days after the end of IVIG and methylprednisolone treatment. After initial rituximab treatment for four weeks, the mRS score and number of CD19+ B cells in all patients were significantly lower than those before treatment (P < 0.05). At the last follow-up (44.1 months, 17.7 S.D.), all patients had recovered well (mRS ≤2), 14 patients (77.8%) recovered completely (mRS = 0), three patients had recurrent seizures, and one patient had mental and language impairment. Two patients had transient mild adverse events during infusion, and none of the other patients experienced severe adverse events during hospitalization or follow-up. ConclusionsRituximab appears safe and may be effective for the treatment of anti-NMDAR encephalitis without tumor in children refractory to first-line agents.

Structural and functional mechanisms of anti-NMDAR autoimmune encephalitis.

Autoantibodies against neuronal membrane proteins can manifest in autoimmune encephalitis, inducing seizures, cognitive dysfunction and psychosis. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most dominant autoimmune encephalitis; however, insights into how autoantibodies recognize and alter receptor functions remain limited. Here we determined structures of human and rat NMDARs bound to three distinct patient-derived antibodies using single-particle electron cryo-microscopy. These antibodies bind different regions within the amino-terminal domain of the GluN1 subunit. Through electrophysiology, we show that all three autoantibodies acutely and directly reduced NMDAR channel functions in primary neurons. Antibodies show different stoichiometry of binding and antibody-receptor complex formation, which in one antibody, 003-102, also results in reduced synaptic localization of NMDARs. These studies demonstrate mechanisms of diverse epitope recognition and direct channel regulation of anti-NMDAR autoantibodies underlying autoimmune encephalitis.

Clinical characteristics and outcomes of patients with antibody-related autoimmune encephalitis presenting with disorders of consciousness: A prospective cohort study.

To explore the clinical characteristics, short- and long-term functional outcomes, and risk factors for antibody-related autoimmune encephalitis (AE) in patients with disorders of consciousness (DoC). Clinical data were collected from AE patients admitted to Xuanwu Hospital of Capital Medical University from January 2012 to December 2021, and patients were followed up for up to 24 months after immunotherapy. A total of 312 patients with AE were included: 197 (63.1%) with anti-NMDAR encephalitis, 71 (22.8%) with anti-LGI1 encephalitis, 20 (6.4%) with anti-GABAbR encephalitis, 10 (3.2%) with anti-CASPR2 encephalitis, 10 (3.2%) with anti-GAD65 encephalitis, and 4 (1.3%) with anti-AMPAR2 encephalitis. Among these patients, 32.4% (101/312) presented with DoC, and the median (interquartile range, IQR) time to DoC was 16 (7.5, 32) days. DoC patients had higher rates of various clinical features of AE (p < .05). DoC was associated with elevated lumbar puncture cerebrospinal fluid (CSF) pressure, CSF leukocyte count, and specific antibody titer (p < .05). A high percentage of patients in the DoC group had a poor prognosis at discharge and at 6 months after immunotherapy (p < .001), but no significant difference in prognosis was noted between the DoC group and the non-DoC group at 12 and 24 months after immunotherapy. Dyskinesia (OR = 3.266, 95% CI: 1.550-6.925, p = .002), autonomic dysfunction (OR = 5.871, 95% CI: 2.574-14.096, and p < .001), increased CSF pressure (OR = 1.007, 95% CI: 1.001-1.014, p = .046), and modified Rankin scale (mRS) score ≥3 at the initiation of immunotherapy (OR = 7.457, 95% CI: 3.225-18.839, p < .001) were independent risk factors for DoC in AE patients. DoC is a relatively common clinical symptom in patients with AE, especially critically ill patients. Despite requiring longer hospitalization, DoC mostly improves with treatment of the primary disease and has a good long-term prognosis after aggressive life support and combination immunotherapy.

Anti-NMDAR1 antibody impairs dendritic branching in immature cultured neurons.

Anti-N-methyl D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder characterized by IgG antibodies targeting NMDAR. The prevalence is remarkably higher in women and some develop the condition during pregnancy. While immunotherapies have shown good outcomes for pregnant mothers and their infants, the impact on early neurodevelopment remains elusive. This study investigates the effects of anti-NMDAR antibody on the development of primary cortical cultures. Anti-NMDAR antibody was administered to the cultures at day in vitro 5 for the following 5 days to assess dendritic branching and arbor complexity, and at day in vitro 14 for measuring the expression of brain-derived neurotrophic factor (BDNF) and synaptic proteins. Immature cultured neurons treated with anti-NMDAR antibody exhibited impaired dendritic branching and arbor complexity. Interestingly, BDNF expression was unaffected in mature neurons. Additionally, GluN1 expression, a mandatory NMDAR subunit, was significantly reduced, while no significant alterations were observed in PSD-95, gephyrin and synaptophysin expression. These findings shed light on the structural and synaptic impacts of anti-NMDAR antibody on immature neurons, providing evidence for their consequences in early neuronal development.

Post-Herpetic Anti-NMDAR Encephalitis in Denmark: Current Status and Future Challenges.

It is well known that N-methyl-D-aspartate receptor encephalitis (NMDARE) can be triggered by infectious encephalitis such as herpes simplex virus 1 encephalitis (HSE). However, the incidence of post-HSE NMDARE in Denmark is unknown. We reviewed literature cases and compared these to retrospectively identified cases of post-HSE NMDARE in Denmark, using a national cohort database of autoimmune encephalitis (AE) and two regional databases of infectious encephalitis patients. We identified 80 post-HSE NMDARE cases in the literature, 66% being children, who more often presented movement disorders, decreased consciousness, and sleep disturbances compared to adults. Eight patients with post-HSE NMDARE were identified from the national cohort database of AE, none being children. Forty-four HSE patients were identified from the regional infectious encephalitis databases. Of these, 16 (36%) fulfilled the Graus criteria for probable/definite NMDARE, and eight (18%) presented a prolonged/relapsing disease course. Ten (23%) were tested for AE during hospitalization. Six (14%) had leftover cerebrospinal fluid available for retrospective autoantibody testing. One out of these six patients (17%) harbored NMDARE antibodies. Thus, in total, nine post-HSE NMDARE patients have been identified in Denmark from 2009 to 2021. Comparing the adult Danish patients to the literature, Danish patients were older, but the clinical phenotype and paraclinical findings were similar. Overall, the incidence of adult post-HSE NMDARE in the Region of Southern Denmark was 0.17 per million people per year and only 7% of adult HSE patients in the region were diagnosed with post-HSE NMDARE. Our findings suggest that adult patients are still underdiagnosed and the absence of pediatric cases diagnosed with post-HSE NMDARE in Denmark is highly concerning.

Differences in the clinical presentations of anti-NMDAR (anti-N-methyl-D-aspartate receptor) encephalitis with status epilepticus: a retrospective case series

Literature on anti-NMDAR (anti-N-methyl-D-aspartate receptor) encephalitis is limited in developing countries, including Indonesia. This retrospective observational case series explored the impact of early diagnosis and treatment on patient outcomes in four distinct cases of anti-NMDAR encephalitis with status epilepticus, and other related conditions, of patients referred to Dr. Sardjito General Hospital, Yogyakarta. Clinical data from May 2021 to August 2023 were collected through the review of medical records, encompassing demographic information, clinical presentation, history, laboratory results, imaging studies, EEG reports, interventions, and the progression of the disease. Four cases were reported, three of whom were diagnosed with anti-NMDAR and one with bacterial encephalitis, each presenting a variety of neuropsychiatric clinical symptoms, leading to hospitalization, extensive testing, and interventions to establish the definitive diagnosis. Cases 1 and 4 have a childhood history of seizures. The cases analyzed factors including the impact of childhood versus adulthood onset and the adherence to taking medicine regularly leading to exacerbation symptoms and relapses. Distinguishing anti-NMDAR encephalitis from related conditions, such as bacterial encephalitis, was further complicated in patients with varied neuropsychiatric presentations (seizures, hallucinations, irritable behavior, headaches) and responses to the treatment. Supporting investigation finds positive NMDAR testing and abnormal CT, MRI, and EEG results, contributed to definitive diagnoses. It could be concluded that comprehensive diagnostic investigations are important for prompt recognition of clinical characteristics, and early initiation of immunomodulatory therapy in managing anti-NMDAR encephalitis and related conditions in Yogyakarta, Indonesia.

Ovarian teratoma-associated Anti-NMDAR encephalitis in women with first-time neuropsychiatric symptoms: A meta-analysis and systematic review of reported cases

ObjectiveAnti-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. MethodsLiterature searches were carried out using PubMed, Scopus, and Web of Science Core Collection. The following data were retrieved: authors' names, year of publication, type of study, number and age of patients included, diagnostic methods of disease evaluation, prevalence of anti-NMDAR antibodies, psychiatric manifestations, other symptoms, initial diagnosis, treatment strategies, and histopathology results. Data analyses were performed and considered statistically significant when p < 0.05. ResultsOur study included 98 female patients with encephalitis associated with a teratoma. The study group reported specific symptoms more often than expected in the general population (p < 0.05). The incidence of seizures deviated most from rates in the general population. The major significant differences were observed in cases of psychosis, seizures, hypoventilation, aphasia, and coma. ConclusionsTeratoma-associated anti-NMDAR encephalitis diagnosis should be systematically investigated in patients presenting with first-time psychotic episodes. Prompt diagnosis and treatment are imperative for prevention of disease progression and better outcomes. Screening and identification of anti-NMDAR antibodies and considering the association of ovarian teratoma and neuropsychiatric symptoms suggesting encephalitis are critical for establishing the proper diagnosis.

Development of a short-term prognostic model for anti-N-methyl-D-aspartate receptor encephalitis in Chinese patients

BackgroundRecognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses.MethodsA prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome.ResultsThis study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p < 0.001; 12-month prognosis, OR 15.756, 95%CI 3.384–73.075, p < 0.001; 24-month prognosis, OR 5.500, 95%CI 1.045–28.955, p = 0.044). Abnormal behavior or cognitive dysfunction (OR 8.57, 95%CI 1.48–49.79, p = 0.017), consciousness impairment (OR19.32, 95%CI 3.03-123.09, p = 0.002), autonomic dysfunction or central hypoventilation (OR 5.66, 95%CI 1.25–25.75, p = 0.025), CSF pleocytosis (OR 4.33, 95%CI 1.48–12.65, p = 0.007), abnormal EEG (OR 5.48, 95% CI 1.09–27.54, p = 0.039) were independent predictors for a poor short-term prognosis after first-line immunotherapy. A nomogram that incorporated those factors showed good discrimination and calibration abilities. The area under the curve (AUC) for the prognostic model were 0.866 (95%CI: 0.798–0.934) with a sensitivity of 0.761 and specificity of 0.869.ConclusionWe established and validated a prognostic model that can provide individual prediction of short-term prognosis after first-line immunotherapy for patients with anti-NMDAR encephalitis. This practical prognostic model may help neurologists to predict the short-term prognosis early and potentially assist in adjusting appropriate treatment timely.

Нейропсихиатрия: психозы, которые не всегда следует лечить антипсихотиками

Disorders manifested by both neurological and mental disorders belong to the neuropsychiatric diseases. This category includes Alzheimer's disease, Parkinson's disease, Wernicke–Korsakoff syndrome, delirium tremens, catatonia and anti-NMDA receptor encephalitis. The etiology of psychotic disorders in neuropsychiatric diseases probably differs from that in schizophrenia and other psychoses, which causes both inefficiency and adverse events when using antipsychotics in neuropsychiatry. In the absence of a therapeutic alternative, antipsychotics can be prescribed with caution for neurodegenerative disorders, whereas catatonia is a relative, and anti-NMDA receptor encephalitis is an absolute contraindication to their use.

Absence of Cerebrospinal Fluid Pleocytosis in Encephalitis.

Early diagnosis of encephalitis involves identifying signs of neuroinflammation, including cerebrospinal fluid (CSF) pleocytosis. However, absence of CSF pleocytosis in encephalitis has been described, most notably in autoimmune encephalitis. We examined clinical characteristics and outcomes associated with the absence or presence of CSF white blood cell pleocytosis (≥ 5 cells/µL), to inform timely diagnosis and management of encephalitis. This retrospective study compares initial CSF profiles in 597 adult patients with all-cause encephalitis. Of the 597 patients, 446 (74.7%) had CSF pleocytosis while 151 (25.3%) did not. CSF pleocytosis occurred more commonly in infectious cases (200/446, 44.8%), along with 59 (13.2%) autoimmune cases, comprised chiefly of anti-NMDAR encephalitis (37/59, 62.7%). Notably, the group without pleocytosis was comprised of similar proportions of infectious (47/151, 31.1%) and autoimmune (38/151, 25.92%; p>0.05) encephalitis. Among those with infectious encephalitis, 47/247 (19%) had absent pleocytosis, including 18/76 (23.7%) with HSV-1 encephalitis. The absence of pleocytosis was associated with a decreased rate of acyclovir administration (47.7% in patients without pleocytosis vs. 71.1% in patients with pleocytosis, p<0.001). Despite pleocytosis being associated with some measures of clinical severity at admission such as a Full Outline of UnResponsiveness (FOUR) score ≤14, it was not associated with mortality or prolonged hospitalization. CSF pleocytosis is an important criterion for encephalitis diagnosis, but 25.3% of patients with all-cause encephalitis and 23.7% of those with HSV-1 encephalitis exhibit absence of pleocytosis on initial LP. Acyclovir initiation should not be delayed in the absence of pleocytosis in patients with suspected encephalitis.

Anti-NMDAR Encephalitis developing neuroleptic malignant syndrome.

Anti-NMDAR Encephalitis developing neuroleptic malignant syndrome.

Eigenvector Centrality Mapping Reveals Volatility of Functional Brain Dynamics in Anti-NMDA Receptor Encephalitis

BackgroundAnti-NMDA receptor encephalitis (NMDARE) causes long-lasting cognitive deficits associated with altered functional connectivity. Eigenvector centrality (EC) mapping represents a powerful new method for data-driven voxelwise and time-resolved estimation of network importance—beyond changes in classical static functional connectivity. MethodsTo assess changes in functional brain network organization, we applied EC mapping in 73 patients with NMDARE and 73 matched healthy control participants. Areas with significant group differences were further investigated using 1) spatial clustering analyses, 2) time series correlation to assess synchronicity between the hippocampus and cortical brain regions, and 3) correlation with cognitive and clinical parameters. ResultsDynamic, time-resolved EC showed significantly higher variability in 13 cortical areas (familywise error p < .05) in patients with NMDARE compared with healthy control participants. Areas with dynamic EC group differences were spatially organized in centrality clusters resembling resting-state networks. Importantly, variability of dynamic EC in the frontotemporal cluster was associated with impaired verbal episodic memory in patients (r = −0.25, p = .037). EC synchronicity between the hippocampus and the medial prefrontal cortex was reduced in patients compared with healthy control participants (familywise error p < .05, tmax = 3.76) and associated with verbal episodic memory in patients (r = 0.28, p = .019). Static EC analyses showed group differences in only one brain region (left intracalcarine cortex). ConclusionsWidespread changes in network dynamics and reduced hippocampal-medial prefrontal synchronicity were associated with verbal episodic memory deficits and may thus represent a functional neural correlate of cognitive dysfunction in NMDARE. Importantly, dynamic EC detected substantially more network alterations than traditional static approaches, highlighting the potential of this method to explain long-term deficits in NMDARE.

A case report of lymphoproliferative disease in brain following therapies with mycophenolate Mofetil and Fingolimod and literature review

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder. With the method of indirect immunofluorescence assay (IIF), more anti-NMDAR encephalitis patients have been discovered when its first onset. But it was rare that anti-NMDAR encephalitis overlapped with multiple sclerosis (MS) documented in literatures. Here, we present a case who initially developed anti-NMDAR encephalitis and MS. Furthermore, we concluded the characteristics of patients who were diagnosed as anti-NMDAR encephalitis overlapping with MS. Additionally, due to the relapsing process, mycophenolate mofetil and sequentially fingolimod for the treatment were taken, which subsequently led to the development of a lymphoproliferative disease in his brain and other organs. This case illustrates the complex role of immunosuppressive agents.

Ketamine alleviates NMDA receptor hypofunction through synaptic trapping

Activity-dependent modulations of N-methyl-D-aspartate glutamate receptor (NMDAR) trapping at synapses regulate excitatory neurotransmission and shape cognitive functions. Although NMDAR synaptic destabilization has been associated with severe neurological and psychiatric conditions, tuning NMDAR synaptic trapping to assess its clinical relevance for the treatment of brain conditions remains a challenge. Here, we report that ketamine (KET) and other clinically relevant NMDAR open channel blockers (OCBs) promote interactions between NMDAR and PDZ-domain-containing scaffolding proteins and enhance NMDAR trapping at synapses. We further show that KET-elicited trapping enhancement compensates for depletion in synaptic receptors triggered by autoantibodies from patients with anti-NMDAR encephalitis. Preventing synaptic depletion mitigates impairments in NMDAR-mediated CaMKII signaling and alleviates anxiety- and sensorimotor-gating-related behavioral deficits provoked by autoantibodies. Altogether, these findings reveal an unexpected dimension of OCB action and stress the potential of targeting receptor anchoring in NMDAR-related synaptopathies.

An elderly case of paraneoplastic anti-NMDA receptor encephalitis associated with large cell neuroendocrine carcinoma of the lung

BackgroundRecent studies have suggested that N-methyl-D-aspartate (NMDA) receptors are involved in the cell proliferation in several tumors. However, there have been no reports demonstrating the expression of NR1 subunit of the NMDA receptor in large cell neuroendocrine carcinoma (LCNEC).Case presentationHere, we report the first elderly case of paraneoplastic anti-NMDA receptor encephalitis associated with LCNEC of the lung with NR1 expression. Of note, NR1 subunit expression in the tumor cells of the present case was confirmed by immunohistochemistry (IHC). Radiation therapy and immunotherapies, such as corticosteroids and intravenous immunoglobulin (IVIG), shrank the tumors and improved neurological symptoms in the present case. Additionally, we also confirmed the expression of NR1 in the tumor cells obtained from three other cases with LCNEC of the lung at our hospital by IHC.ConclusionOur IHC results indicate that LCNEC generally expresses NR1 subunit and NMDA receptor may be involved in the tumor development and growth.