Recent research on cytokines associated with anti-N-methyl-D-aspartate receptor encephalitis / 中国当代儿科杂志

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune inflammatory disease of the central nervous system, and little is known about its immune mechanism at present. There is a lack of disease-related biomarkers in cerebrospinal fluid except anti-NMDAR antibody, which leads to delayed diagnosis and treatment in some patients. Therefore, there has been an increasing number of studies on related cytokines in recent years to assess whether they can be used as new biomarkers for evaluating disease conditions and assisting diagnosis and treatment. Current studies have shown that some cytokines may be associated with the progression of anti-NMDAR encephalitis, and this article reviews the research advances in such cytokines associated with anti-NMDAR encephalitis.

Abnormal topology of cortical thickness covariance network and altered functional connectivity in patients with anti-N-methyl-D-aspartate receptor encephalitis / 中华行为医学与脑科学杂志

Objective:To explore the changes in topological attributes of structural covariance network based on cortical thickness and the brain functional activities in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis by graph theory and functional connectivity (FC) analyses, and to investigate whether these changes were correlated to cognitive impairment.Methods:A total of 33 patients with anti-NMDAR encephalitis from Department of Neurology of the First Affiliated Hospital of Guangxi Medical University(patient group) and 35 healthy controls(control group) with matched gender, age, and education were included from July 2018 to November 2021.All subjects received cognitive function assessments, structural and functional magnetic resonance imaging scans.Structural covariance networks were constructed in the two groups based on cortical thickness values and topological characteristics of networks were computed.A non-parametric permutation test which repeated 1 000 times was used to compare the characteristics of the networks between the two groups.Brain regions with abnormal topology were defined as region of interest(ROI), and FC values in global brain level were calculated.SPM 12 and RESTplus were used to identify the brain regions with significant differences in FC values between the two groups.Finally, Spearman correlation analysis between FC values of significant brain regions and cognitive scores were performed by SPSS 24.0.Results:The cognitive score of patients with anti-NMDAR encephalitis (27.0(23.5, 28.0)) was lower than that in control group(29.0(27.0, 30.0)) ( Z=-3.029, P=0.002). Graph theory analysis found that the patients showed significantly increased clustering coefficients ( P=0.004) and decreased global efficiency ( P=0.004) compared with healthy controls.Moreover, the nodal efficiency of left ventral posterior cingulate cortex (vPCC) and right dorsal posterior cingulate cortex (dPCC), as well as the nodal degree centrality of left vPCC and left polar planum of superior temporal gyrus (ppSTG) in patient group were significantly decreased ( P<0.05, FDR corrected) compared with control group.FC analysis showed the increased FC values between left vPCC and posterior cerebellum (MNI: x=6, y=-66, z=-21), as well as between left ppSTG and anterior cerebellum (MNI: x=6, y=-54, z=-12) (GRF corrected, voxel level P<0.001, cluster level P<0.05) in patient grooup.The FC values between left vPCC and posterior cerebellum were negatively correlated with the cognitive scores ( r=-0.403, P=0.020). Conclusion:Patients with anti-NMDAR encephalitis show abnormal topology of structural covariance network based on cortical thickness and altered FC values, some of which are correlated to cognition and may be the underlying neural mechanism of cognitive impairment in patients with anti-NMDAR encephalitis.

Encefalitis inmunomediada en un niño con antecedente de infección por SARS-CoV-2 n / Immune-mediated encephalitis in a child with a history of SARS-CoV-2 infectio

Las encefalitis son cuadros clínicos frecuentes en la edad pediátrica. Pueden dividirse en aquellas causadas por la infección del sistema nervioso central y en las de etiología inmunomediada (algunas de las cuales pueden ser para- o posinfecciosas). En marzo de 2020 la Organización Mundial de la Salud declaró la pandemia por el coronavirus de tipo 2 del síndrome respiratorio agudo grave (SARS-CoV-2, por su sigla en inglés). Los reportes pediátricos de enfermedad por dicho agente describen una amplia gama de manifestaciones clínicas: compromiso respiratorio, gastrointestinal, síntomas neurológicos, entre otros; y el síndrome inflamatorio multisistémico asociado a COVID-19 (SIM-C). Describimos el caso de un niño de 2 años con diagnóstico de encefalitis por anticuerpos antirreceptor N-metil-d-aspartato (anti-NMDAR), en quien se comprobó, mediante serología, una infección reciente por SARS-CoV-2. La presencia de marcadores serológicos positivos para SARS-CoV-2 en un paciente que presentó encefalitis por anticuerpos anti-NMDAR podría interpretarse como una asociación temporal, estableciéndose la posibilidad de que el virus haya actuado como gatillo de una enfermedad autoinmunitaria.

Encephalitis are frequent clinical pictures in pediatric age. They can be divided into those caused by infection of the central nervous system and those of immune-mediated etiology (some of which may be para- or post-infectious). In March 2020, the WHO declared a SARS-CoV-2 pandemic. Pediatric reports of disease caused by this agent describe a wide range of clinical manifestations: respiratory and gastrointestinal compromise, neurological symptoms, among others; and a multisystemic inflammatory syndrome in children associated with COVID-19 (MIS-C).We describe the case of a 2-year-old boy with a diagnosis of anti-NMDAR antibody encephalitis, in whom a recent SARSCoV-2 infection was serologically proven. The presence of positive serological markers for SARS-CoV-2 in a patient who presented encephalitis due to anti-NMDAR antibodies could be interpreted as a temporal association; establishing the possibility that the virus has acted as a trigger for an autoimmune disease

Manejo de Encefalitis anti-NMDAR con Rituximab: Reporte de caso en un Hospital Público de Lima, Perú

Introducción: La encefalitis autoinmune comprende un amplio espectro de desórdenes inmunológicos, entre ellos el anti-NMDAR es el más frecuente. El manejo de esta patología es complejo debido a múltiples circunstancias. Reporte de caso: Mujer de 19 años que inicia cuadro subagudo con trastorno conductual y neurológico asociado: Alucinaciones, heteroagresividad, mutismo acinético, crisis epilépticas, discinesias orofaciales, fiebre y arritmia cardiaca transitoria reportada. La resonancia fue normal, el EEG registró ondas delta brush, Los estudios de LCR y séricos fueron negativos para causas secundarias. Se inició tratamiento con Aciclovir, medicamento anticrisis y psicofármacos, posteriormente se inicia metilprednisolona con inmunoglobulina sin respuesta satisfactoria. Inicia tratamiento con Rituximab presentando una respuesta favorable. El panel en LCR fue positivo a NMDA. Se indica control con desescalamiento progresivo de medicamentos anticrisis y psicofármacos. Conclusión: Es importante reconocer tempranamente las manifestaciones clínicas de esta entidad para así realizar un manejo oportuno que podría mejorar el pronóstico.

Introduction: Autoimmune encephalitis comprises a wide spectrum of immunological disorders, among them anti-NMDAR is the most frequent. The management of this pathology is complex due to multiple circumstances. Case report: A 19-year-old woman who started a subacute clinical picture with associated behavioral and neurological disorder: hallucinations, heteroaggressiveness, akinetic mutism, epileptic seizures, orofacial dyskinesias, fever and reported transient cardiac arrhythmia. MRI was normal, EEG recorded delta brush waves, CSF and serum studies were negative for secondary causes. Treatment was started with Acyclovir, an anti-crisis drug, and psychotropic drugs, later methylprednisolone with immunoglobulin was started without a satisfactory response. She starts treatment with Rituximab presenting a favorable response. The CSF panel was positive for NMDA. Control with progressive de-escalation of anti-crisis medications and psychotropic drugs is indicated. Conclusion: It is important to recognize early the clinical manifestations of this entity in order to carry out timely management that could improve the prognosis.

Encefalitis anti-receptor NMDA: un diagnóstico a considerar / Anti- receptor NMDA encephalitis, a diagnosis to consider

Resumen Las encefalitis son trastornos inflamatorios cerebrales, secundarias a diferentes procesos patológicos que incluyen causas infecciosas y autoinmunes. En los últimos años se han estudiado los procesos autoinmunes involucrados, con una creciente identificación de casos donde presenta una amplia variedad de síntomas neurológicos y psiquiátricos que suelen dificultar el diagnóstico oportuno. Por tanto, esta es una revisión narrativa que describe los principales aspectos de la encefalitis por anticuerpos contra el receptor de N-metil-D-aspartato (NMDAR), su patogénesis (mecanismo que comparte con los trastornos psicóticos), diagnóstico y presentación clínica; aspectos que destacan la importancia de una evaluación exhaustiva de las manifestaciones psiquiátricas en el ámbito clínico.

Abstract Encephalitis are inflammatory brain disorders that are secondary to different pathological processes that include infectious and autoimmune causes. In recent years, the autoimmune processes involved have been studied with an increment in the identification of cases that present a wide variety of neurological and psychiatric symptoms, which often make their timely diagnosis difficult. This is a narrative review that describes the main aspects of encephalitis caused by antibodies against the N-methyl-D-aspartate receptor (NMDAR), its pathogenesis (mechanism shared with psychotic disorders), diagnosis, and clinical presentation; these are aspects that highlight the importance of a thorough evaluation of psychiatric manifestations in the clinical setting.

A critical review and update on autoimmune encephalitis: understanding the alphabet soup / Revisão crítica e atualizações em encefalites autoimunes: entendendo a sopa de letrinhas

ABSTRACT Autoimmune encephalitis (AE) comprises a group of diseases mediated by antibodies against neuronal cell surface or synaptic antigens, such as ion channels or neurotransmitter receptors. New clinical syndromes and their associated antibodies were and are still being characterized over the last two decades. The fact that their main clinical features are interdisciplinary, - encompassing neuropsychiatric symptoms, cognitive dysfunction, epileptic seizures, movement and sleep disorders - has led to a surge of interest in this field. Some of these diseases present with a well-defined syndrome, being recognizable on clinical grounds. Correct diagnosis is important since AE are potentially treatable diseases, despite their severity. On the other hand, an increasing number of neuronal antibodies being described casts doubt upon the way we should utilize antibody testing and interpret results. In this article we review, summarize and update the current knowledge on antibody mediated encephalitis.

RESUMO As encefalites autoimunes compreendem um grupo de doenças mediadas por anticorpos contra antígenos de superfície neuronal ou sinapse, como canais iônicos ou receptores de neurotransmissores. Novas síndromes clínicas e os anticorpos a elas associados foram e ainda estão sendo caracterizados ao longo das últimas duas décadas. Dado que suas principais características clínicas são interdisciplinares, isto é, incluem -se sintomas neuropisquiátricos, disfunção cognitiva, crises epilépticas, distúrbio do movimento e do sono, há uma grande onda de interesse sobre esse campo de conhecimento. Algumas dessas doenças apresentam-se com uma síndrome bem definida, sendo possível reconhecê-las clinicamente. Diagnosticá-las corretamente é importante uma vez que se trata de doenças potencialmente tratáveis apesar da gravidade que lhes é característica. Por outro lado, o número crescente de anticorpos sendo descritos causam dúvida frequente sobre qual o melhor teste a solicitar e como interpretá-los. Nós aqui apresentamos uma revisão atualização resumida do conhecimento atual sobre as encefalites mediadas por anticorpos.

Encefalitis por anticuerpos contra el receptor N-metil-D-aspartato secundaria a teratoma ovárico en una paciente pediátrica / Encephalitis due to antibodies against the N-methyl-D-aspartate receptor secondary to ovarian teratoma in a pediatric patient

La encefalitis por anticuerpos contra el receptor N-metilD-aspartato es un proceso inmunomediado en el que autoanticuerpos se dirigen contra la subunidad GluN1 del receptor de glutamato del sistema nervioso central. Se caracteriza por la aparición aguda o subaguda de síntomas psiquiátricos, como confusión, pérdida de la memoria a corto plazo, cambios de conducta, catatonía, seguidos por manifestaciones neurológicas, tales como convulsiones, alteraciones del movimiento, disfunciones autonómicas, coma y depresión respiratoria. Es grave y potencialmente mortal. Su asociación con teratoma de ovario como síndrome paraneoplásico fue descrita en mujeres jóvenes. En la población pediátrica, es mucho menos frecuente y se reporta en comunicaciones de 1 o 2 pacientes y en series de pocos casos. Se presenta una paciente de 13 años con encefalitis paraneoplásica por anticuerpos contra el receptor N-metil-Daspartato, secundaria a un teratoma ovárico maduro.

The encephalitis due to antibodies against the N-methylD-aspartate receptor is a process immune-mediated in which antibodies are directed against the GluN1 subunit of the glutamate receptor in the central nervous system. It is characterized by an acute or subacute onset of psychiatric symptoms such as confusion, short-term memory loss, behavioral changes, catatonia followed by neurological manifestations such as seizures, movement disturbances, autonomic dysfunctions, coma, and respiratory depression. It is serious and life threatening. Its association with ovarian teratoma as a paraneoplastic syndrome was described in youngwomen. In the pediatric population it is much less frequent and is reported in publications of one or two patients and in series of few cases. We present a 13-year-old patient with encephalitis paraneoplastic due to antibodies against the N-methyl-Daspartate receptor, secondary to a mature ovarian teratoma.

Recent advance in experimental animal models of anti-N-methyl-D-aspartate receptor encephalitis / 中华神经科杂志

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis mediated by anti-NMDAR antibody. At present, the pathogenesis of the disease is not completely clear, and reliable animal models are of great significance for the study of its pathogenesis and pathophysiological process. The authors reviewed the reports of anti-NMDAR encephalitis′s animal models in recent years, and discussed the advantages and limitations of each model, in order to provide a more suitable animal model for further research on anti-NMDAR encephalitis.

Characteristics of brain glucose metabolism in patients with anti- N-methyl- D-aspartate receptor encephalitis underlying different inducing factors / 中华核医学与分子影像杂志

Objective:To investigate characteristics and differences of cerebral glucose metabolism in patients with anti- N-methyl- D-aspartate receptor (NMDAR) encephalitis from the perspective of different trigger factors of antibodies. Methods:A total of 15 patients (8 males, 7 females, age (30.5±17.7) years) with anti-NMDAR encephalitis between January 2016 and January 2019 in Huashan Hospital, Fudan University were recruited retrospectively. All patients underwent resting state cerebral 18F-FDG PET imaging. The characteristics of brain glucose metabolism were analyzed, and the SUV ratio (SUVR) was semi-quantitatively compared with that in 12 healthy subjects (HS; 7 males, 5 females, age (51.5±9.6) years). Independent-sample t test was used to analyze the data. Results:Among 15 patients, 5 patients were viral encephalitis-related anti-NMDAR encephalitis, showing focal decreased metabolism in unilateral temporal lobe or basal ganglia (SUVR: patients: 0.659±0.219; HS: 1.754±0.203; t=-9.58, P<0.001), with increased metabolism in contralateral temporal lobe or basal ganglia (SUVR: patients: 2.275±0.244; HS: 1.960±0.227; t=2.55, P=0.022) in 18F-FDG PET imaging. Six patients were cryptogenic anti-NMDAR encephalitis, showing asymmetric increased metabolism in frontal, temporal, parietal and basal ganglia (SUVR: patients: 2.482±0.395; HS: 1.754±0.203; t=5.23, P<0.001), with decreased metabolism in bilateral occipital lobes. The remaining 4 cases were paraneoplastic origin accompanied by teratoma, showing increased metabolism in bilateral temporal and basal ganglia (SUVR: patient: 2.359±0.181; HS: 1.960±0.227; t=3.16, P=0.007), with mild decreased metabolism in bilateral occipital lobe. Conclusions:The abnormal changes of cerebral glucose metabolism in patients with anti-NMDAR encephalitis can be divided into at least three patterns according to different trigger factors. A comprehensive understanding of these characteristic metabolic changes is helpful for detecting disease, and may provide potential value in indicating different causes.

Reporte de un caso fatal de encefalitis autoinmunitaria asociada a teratoma ovárico / Report of a fatal case of autoimmune encephalitis associated with an ovarian teratoma

INTRODUCCIÓN: El teratoma del ovario es el tumor de células germinales más frecuente. Entre sus complicaciones se describen algunos síndromes paraneoplásicos, como la encefalitis por anticuerpos contra el receptor N-metil-D-aspartato (NMDA). CASO CLÍNICO: Mujer de 22 años sin antecedentes de importancia que consulta por cuadro clínico de 4 días de evolución caracterizado por síntomas psiquiátricos y un episodio convulsivo. Se considera un cuadro de meningoencefalitis y se indica manejo antibiótico de amplio espectro y antiviral. Ante el deterioro se sospecha una encefalitis autoinmunitaria, se identifica un tumor anexial en los estudios imagenológicos compatible con teratoma y se confirma el diagnóstico con el hallazgo de anticuerpos NMDA en el líquido cefalorraquídeo. A pesar de su resección y manejo sistémico, fallece a los 5 meses. DISCUSIÓN: La encefalitis autoinmunitaria asociada a un teratoma es inusual, pero es una complicación que debe sospecharse como diagnóstico de exclusión. La mayoría tienen un pronóstico favorable, aunque hasta una cuarta parte de los casos puede asociarse a daño irreversible en la corteza del hipocampo e incluso la muerte, principalmente cuando el diagnóstico y el tratamiento son tardíos. CONCLUSIONES: Este caso es un reto clínico que representa un vacío en la evidencia actual, puesto que no existe un estándar de manejo de los teratomas. Se propone que, una vez diagnosticado un teratoma, se realice una cistectomía ovárica. Son necesarios más estudios para validar esta recomendación.

INTRODUCTION: The ovarian teratoma is the most common cell germ tumor. Some paraneoplastic syndromes have been described, including the anti-N-methyl-D-aspartate (NMDA) receptor encephalitis as part of its complications. CASE REPORT: A 22 years old female patient with no important medical history, consults due to an acute psychotic disorder and a convulsion. A meningoencephalitis was considered and broad-spectrum antibiotics and antivirals were started. Faced with deterioration, an autoimmune encephalitis is considered as well. Imaging studies revealed an ovarian teratoma and diagnosis was confirmed with antibodies against NMDA receptor in cerebrospinal fluid. Despite its resection and systemic management, the patient dies after 5 months. DISCUSSION: The autoimmune encephalitis associated with an ovarian teratoma is rare, its a complication that must be suspected as an exclusion diagnosis and most have a favorable prognosis, however up to a quarter of cases can be associated with irreversible damage to the hippocampal cortex and even death, mainly when late diagnosis and treatment are made. CONCLUSIONS: This case is a clinical challenge, no evidence is available since there is no standard for teratoma management. It is proposed that once a teratoma is diagnosed, an ovarian cystectomy is performed. Further studies are necessary to validate this recommendation.

Therapeutic strategies of pediatric anti-N-methyl-D-aspartate receptor encephalitis / 中国小儿急救医学

Anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis is an autoimmune disorder mediated by anti-NMDAR antibody.It can be found in both adults and children.Anti-NMDAR encephalitis in children is different from adults in inducement, clinical manifestation, diagnosis process, treatment, follow-up strategy, and prognosis.Although the clinical manifestation of the disease is serious, timely and effective immunotherapy can make the vast majority of children get a good prognosis.Therefore, the review summarized and analyzed the treatment progress, in order to improve the standard diagnosis and treatment of pediatric anti-NMDAR encephalitis in China, and reduce the morbidity and mortality.

Cryptococcal Encephalitis Complicating Anti-N-methyl-D-aspartate Receptor Encephalitis in an Immunosuppressed Patient / 中国医学科学院学报

Cryptococcal encephalitis is a fatal central nervous system infectious disease,whereas anti-N-methyl-D-aspartate(NMDA)receptor encephalitis(NMDARE)is an autoimmune syndrome associated with psychological symptoms,behavioural abnormalities,seizures,and dyskinesias.Despite their distinct pathologies and pathogenic mechanisms,both of them can lead to cognitive dysfunction and abnormal behaviors,although anti-NMDARE can also have mood and mental disorders as its core manifestations.A patient with nephrotic syndrome accompanied by both cryptococcal encephalitis and anti-NMDARE was treated in our center,which for the first confirmed that these two conditions could coexist in one patient.The underlying mechanism may be similar to that of anti-NMDARE after other infections.

Clinical characteristics of antiNmethylaspartate receptor encephalitis in children / 中南大学学报(医学版)

OBJECTIVES@#To analyze the clinical characteristics and prognosis of children with anti-N-methyl--aspartate receptor (NMDAR) encephalitis and to provide a basis for early clinical identification of this disease.@*METHODS@#The clinical data of 42 cases of anti-NMDAR encephalitis at Department of Pediatrics, Second Xiangya Hospital, Central South University from January 2015 to March 2018 were collected. The clinical features and followed-up outcomes were analyzed retrospectively.@*RESULTS@#There were 15 cases (35.7%) of males and 27 cases (64.3%) of females in 42 children, with a ratio of 1꞉1.8. They were aged from 4 months to 17 years, with an average of (9.20±4.66) years. The most common initial symptoms were seizures (47.6%, 20/42) and mental behavior disorder (35.7%, 15/42). During the course of the disease, 85.7% patients(36/42) had mental and behavior disorder, 85.7% patients (36/42) had epilepsy, 76.2% (32/42) had speech disorder, 66.7% patients (28/42) had dyskinesia, 66.7% patients (28/42) had the decreased level of consciousness, 61.9% patients (26/42) had autonomic instability, and 57.1% (24/42) patients had sleep disorder. All the children had positive antibody against NMDA receptor resistance encephalitis in cerebrospinal fluid. Head MRI showed the abnormal incidence was 50.0% (21/42), and the lesions involved in parietal lobe, frontal lobe, temporal lobe, occipital lobe, midbrain, thalamus, basal ganglia and optic nerve. There was a patient with optic nerve damage combined with myelin oligodendrocyte glycoprotein (MOG) antibody positive. Forty cases were examined by electroencephalogram (EEG), 92.5% cases (37/40) were abnormal, mainly showing diffuse slow waves, and δ brushes could be seen in severe cases. And there was 1 patient (2.4%) complicated with mesenteric teratoma. The mRS score (2.14±1.46) at discharge was significantly lower than the highest mRS score (3.88±1.38) during hospitalization (<0.05). After 3-39 months of follow-up, mRS score at 3 months after discharge was only 0.81±1.29, which was still improved compared with that at discharge, 76.2% cases (32/42) experienced complete or near-complete recovery (mRS score≤2), and 4.8% (2/42) cases relapsed. There was no mortality; the initial time of immunotherapy and the highest mRS score in the course of the disease were the factors affecting the prognosis. The earlier the starting time for immunotherapy and the lower mRS score in the course of the disease were, the better the prognosis was.@*CONCLUSIONS@#Seizures, mental and behavior disorder, dyskinesias, speech disorder and autonomic instability are common clinical manifestations of anti-NMDAR encephalitis in children. The effect of immunotherapy is significant, and the time to start immunotherapy and the severity of the disease are important factors affecting the prognosis. Anti-NMDAR encephalitis can be combined with other autoantibodies, but its clinical significance and mechanism need further study.

Efficacy of double fltration plasmapheresis on nine patients with severe anti-N-methyl-D-aspartate receptor encephalitis / 第二军医大学学报

Objective: To investigate the therapeutic effect of double filtration plasmapheresis (DFPP) on severe anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and its clinical significance. Methods: We retrospectively analyzed the clinical data from 9 patients with severe anti-NMDAR encephalitis confrmed by Changhai Hospital of Naval Medical University (Second Military Medical University) from Jan. 2014 to Mar. 2018. The 9 patients did not respond to methylprednisolone shock therapy. We collected the clinical manifestations, and examination results of laboratory, electroencephalogram and imaging, and analyzed the therapeutic effect of DFPP. Results: Nine anti-NMDAR encephalitis patients, including 5 females and 4 males, were admitted to neurology intensive care unit. Their ages were ranged from 15 to 69 years old, median age of onset was 37 years old, and average hospital stay was (33.2 ± 7.6) d. The main clinical symptoms were mental behavioral abnormalities (9 cases), autonomic dysfunction (9 cases), seizures (7 cases), central hypopnea (5 cases), and consciousness disorders (5 cases). One patient was complicated with ovarian teratoma. Nine patients were positive for anti-NMDAR antibodies in cerebrospinal fluid, and 7 patients were positive for anti-NMDAR antibodies in serum. All the 9 patients were examined by electroencephalogram, and 7 of them had abnormal findings, mainly with diffuse changes and abnormal slow waves. Brain magnetic resonance imaging showed that abnormal signals could be seen in the frontal lobe, parietal lobe, temporal lobe, hippocampus and other brain regions of 4 patients, and no abnormal signals were found in the other 5 patients. Nine patients were treated with DFPP after ineffective treatment with methylprednisolone, 5 of them recovered completely, and the other 4 cases had significantly improved residual symptoms. Conclusion: DFPP can be used as an alternative for patients with severe anti-NMDAR encephalitis who are not sensitive to glucocorticoid therapy. It has better clinical efficacy and it is not restricted by allogeneic plasma resources.

Early diagnosis of autoimmune encephalitis / 中华实用儿科临床杂志

Autoimmune encephalitis is a group of treatable autoimmune diseases of central nervous system.Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most common autoimmune encephalitis.Some of autoimmune encephalitis can be confirmed by specific autoantibodies, but excessive dependence on autoantibody detection usually leads to delayed treatment.This article reviews the clinical presentations of pediatric anti-NMDAR encephalitis and the antibody-negative autoimmune encephalitis so as to improve the pediatricians understanding on the diseases.

Observation of therapeutic plasma exchange in the treatment of pediatric severe critical anti￣N￣methyl￣D￣aspartate receptor encephalitis / 中国小儿急救医学

Objective To investigate the features and incidence of severe anti-N-methyl-D-aspartate receptor ( NMDAR) encephalitis in pediatric intensive care unit ( PICU) treated with therapeutic plasma exchange(TPE). Methods A retrospective study was conducted of children with severe anti NMDAR encephalitis admitted to PICU of Shanghai Children′s Hospital from July 2015 to June 2018. Demographic data,therapeutic regimens,clinical and laboratory data were analyzed. The one dose of replacement plasma was 50-70 ml/kg. The laboratory biomarkers, anti-NMDAR in serum and cerebrospinal fluid ( CSF) were measured before and after TPE treatment. Results Thirteen cases with anti-NMDAR encephalitis were analyzed. The main clinical features were seizures, unconsciousness, motor dysfunctions organ dysfunction included respiratory failure in 3 (23. 1%) patients and shock in 4 (30. 8%) cases. The average levels of PICU stays were[11. 0(5. 5,19. 0)] days. The conventional therapy included methylprednisolone,intrave-nous immunoglobulin (IVIG),antiepileptic,and immune-suppressants. Seven patients received conventional treatment,and 6 (46. 2%) cases combined TPE after unsatisfactory effect on 3 to 7 days conventional treat-ment. TPE dosage was 50-70 ml/kg body weight per times for 3-5 dosages. The Glasgow coma score(GCS) and pediatric risk of mortality Ⅲ( PRISM Ⅲ) of children after TPE treatment were signifcantly improved compared with those before TPE treatment[ GCS:7. 5(6. 0,9. 3) vs. 12. 5 (11. 5,13. 5),PRISM Ⅲ:15. 5 (9. 5,17. 5) vs. 11. 0(4. 5,12. 3),all P<0. 05]. The levels of anti-NMDAR antibody in both serum and CSF decreased significantly after TPE(all P<0. 05). Three cases (50. 0%) had anaphylaxis during TPE. Conclusion TPE could decease the levels of anti-NMDAR antibody in CSF and serum,improve psychiatric and neurologic symptoms. TPE may be a potential therapy in pediatric severe NMDAR encephalitis.

One case of anti-NMDAR encephalitis combined with NMOSD during pregnancy and literature review / 中国医师杂志

Anti-N-methyl-D-aspartate receptor (N-methyl-D-aspartate receptor,NMDAR) encephalitis is the most common autoimmune encephalitis,mostly in young women of childbearing age,but how pregnancy influence the disease is still unclear.This article reports a case of gestational morbidity,and analyzes 10 pregnant women in different stages and their babies published in domestic and foreign,aiming to briefly explore the influences of different fetuses during pregnancy.

Ovarian tumor associated with anti-N-methyl-D-aspartate receptor encephalitis: A report of 110 cases / 中国医师杂志

Objective To summarize the clinical features of patients with ovarian tumor associated anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis,and to explore the influence of operation patterns on the prognosis.Methods The clinical data of ovarian tumors with anti-NMDAR encephalitis in the Third Affiliated Hospital of Sun Yat-sen University from January 2009 to December 2018 were collected,and the clinical characteristics,treatment and prognosis were analyzed.Results A total of 110 patients with ovarian tumors and anti-NMDAR encephalitis were collected.All patients were positive for anti-NMDAR antibodies in serum and/or cerebrospinal fluid.The age of onset ranged from 10 to 35 years (24.6 ±5.7).About 60.9％ patients'initial symptom was psychosis.The main clinical features were psychosis (97.3％),seizures (83.6％),conscious disturbance (72.7％),autonomic dysfunction (64.5％),dyskinesia (64.5％),central hypoventilation (54.5％) and impaired memory (31.8％).Most patients'symptoms were relieved after surgery and immunotherapy.Postoperative pathological results revealed that ovarian teratoma accounted for 97.8％ of the ovarian tumor.The prognosis of patients with surgery was better than the patients without surgery,with statistically significant difference (P ＜ 0.05).The prognosis of patients with adnexectomy was better than the patients with ovarian tumor excision,with statistically significant difference (P ＜ 0.05).Conclusions Anti-NMDAR encephalitis,with psycho-neurological symptoms as dominant manifestation,is usually associated with ovarian tumor.For young female patients with psychosis,clinicians should be alert to the possibility of anti-NMDAR encephalitis and screen for tumor.Patients with adnexectomy and immunotherapy can get a better prognosis.

Perioperative anesthesia management in patients with anti-N-methyl-D-aspartate receptor encephalitis complicated with ovarian teratoma / 中国医师杂志

Objective To improve the understanding of perioperative anesthesia management in patients with anti-N-methyl-D-aspartate receptor encephalitis combined with a history of ovarian teratoma.Methods Case information of 10 patients with anti-N-methyl-D-aspartate receptor encephalitis with a history of ovarian teratoma admitted to the Third Affiliated hospital of Sun yat-sen University from July 2014 to November 2018 were retrospectively analyzed.Results A total of 10 patients received treatment,8 improved after treatment,2 had poor prognosis,and their families required discharge.All patients received endotracheal intubation under general anesthesia.Conclusions Anesthesiologists should pay attention to perioperative anesthesia management of patients with anti-N-methyl-D-aspartate receptor encephalitis complicated with ovarian teratoma,including preoperative evaluation,anesthesia methods and drug selection,intraoperative and postoperative management.

Identification of anti-NMDA receptor encephalitis in first-episode mental disorders and schizophrenia / 中国医师杂志

Psychiatric symptoms are one of the most common symptoms in patients with anti-N-methyl-D-aspartate (NMDA) receptor encephalitis,which is not specific compared with the symptoms of schizophrenia.Young female patients without previous history of mental disorders have sudden onset of psychiatric symptoms,conscious disturbances or suspicious conscious disturbances,especially in the presence of catatonic,requiring electroencephalogram (EEG) and head magnetic resonance imaging for the identification of anti-NMDA receptor encephalitis.Abnormal NMDA receptor antibody in cerebrospinal fluid is the basis of diagnosis.