Brazilian consensus recommendations on the diagnosis and treatment of autoimmune encephalitis in the adult and pediatric populations / Consenso brasileiro sobre o diagnóstico e o tratamento de encefalites autoimunes nas populações adulta e pediátrica

Abstract Background Autoimmune encephalitis (AIE) is a group of inflammatory diseases characterized by the presence of antibodies against neuronal and glial antigens, leading to subacute psychiatric symptoms, memory complaints, and movement disorders. The patients are predominantly young, and delays in treatment are associated with worse prognosis. Objective With the support of the Brazilian Academy of Neurology (Academia Brasileira de Neurologia, ABN) and the Brazilian Society of Child Neurology (Sociedade Brasileira de Neurologia Infantil, SBNI), a consensus on the diagnosis and treatment of AIE in Brazil was developed using the Delphi method. Methods A total of 25 panelists, including adult and child neurologists, participated in the study. Results The panelists agreed that patients fulfilling criteria for possible AIE should be screened for antineuronal antibodies in the serum and cerebrospinal fluid (CSF) using the tissue-based assay (TBA) and cell-based assay (CBA) techniques. Children should also be screened for anti-myelin oligodendrocyte glucoprotein antibodies (anti-MOG). Treatment should be started within the first 4 weeks of symptoms. The first-line option is methylprednisolone plus intravenous immunoglobulin (IVIG) or plasmapheresis, the second-line includes rituximab and/or cyclophosphamide, while third-line treatment options are bortezomib and tocilizumab. Most seizures in AIE are symptomatic, and antiseizure medications may be weaned after the acute stage. In anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, the panelists have agreed that oral immunosuppressant agents should not be used. Patients should be evaluated at the acute and postacute stages using functional and cognitive scales, such as the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Modified Rankin Scale (mRS), and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Conclusion The present study provides tangible evidence for the effective management of AIE patients within the Brazilian healthcare system.

Resumo Antecedentes Encefalites autoimunes (EAIs) são um grupo de doenças inflamatórias caracterizadas pela presença de anticorpos contra antígenos neuronais e gliais, que ocasionam sintomas psiquiátricos subagudos, queixas de memória e distúrbios anormais do movimento. A maioria dos pacientes é jovem, e o atraso no tratamento está associado a pior prognóstico. Objetivo Com o apoio da Academia Brasileira de Neurologia (ABN) e da Sociedade Brasileira de Neurologia Infantil (SBNI), desenvolvemos um consenso sobre o diagnóstico e o tratamento da EAIs no Brasil utilizando a metodologia Delphi. Métodos Um total de 25 especialistas, incluindo neurologistas e neurologistas infantis, foram convidados a participar. Resultados Os especialistas concordaram que os pacientes com critérios de possíveis EAIs devem ser submetidos ao rastreio de anticorpos antineuronais no soro e no líquido cefalorraquidiano (LCR) por meio das técnicas de ensaio baseado em tecidos (tissue-based assay, TBA, em inglês) e ensaio baseado em células (cell-based assay, CBA, em inglês). As crianças também devem ser submetidas ao rastreio de de anticorpo contra a glicoproteína da mielina de oligodendrócitos (anti-myelin oligodendrocyte glycoprotein, anti-MOG, em inglês). O tratamento deve ser iniciado dentro das primeiras 4 semanas dos sintomas, sendo as opções de primeira linha metilprednisolona combinada com imunoglobulina intravenosa (IGIV) ou plasmaférese. O tratamento de segunda linha inclui rituximabe e ciclofosfamida. Bortezomib e tocilizumab são opções de tratamento de terceira linha. A maioria das crises epilépticas nas EAIs são sintomáticas, e os fármacos anticrise podem ser desmamadas após a fase aguda. Em relação à encefalite antirreceptor de N-metil-D-aspartato (anti-N-methyl-D-aspartate receptor, anti-NMDAR, em inglês), os especialistas concordaram que agentes imunossupressores orais não devem ser usados. Os pacientes devem ser avaliados na fase aguda e pós-aguda mediante escalas funcionais e cognitivas, como Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Modified Rankin Scale (mRS), e Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Conclusão Esta pesquisa oferece evidências tangíveis do manejo efetivo de pacientes com EAIs no sistema de saúde Brasileiro.

Psicosis como manifestación inicial de encefalitis autoinmune contra los receptores N-metil-D-aspartato (ECR-NMDA): reporte de caso / Psychosis as first manifestation of autoimmune encephalitis against N-methyl-D-aspartate receptors (ECR-NMDA). Case Report

RESUMEN Se presenta el caso de un varón de 21 años hospitalizado en el servicio de psiquiatría de un hospital general con historia de alteraciones de pensamiento, percepción y conducta, y que tuvo un intento suicida. En la unidad de hospitalización, el paciente presentó una evolución tórpida, incluyendo la aparición de movimientos involuntarios y un progresivo trastorno sensorial que determinó su traslado a la unidad de cuidados intermedios del servicio de medicina interna. Después de exámenes de laboratorio, apoyo de imágenes y evaluación por diferentes especialidades, el diagnóstico final fue el de un cuadro compatible con encefalitis anti-receptor NMDA.

ABSTRACT The case of a 21-year-old man, hospitalized in the psychiatric service of a general hospital with a history of abnormal thought, perception, and behavioral processes, reaching a suicidal attempt, is presented. In the psychiatric hospitalization unit, he experienced a torpid clinical course, including the appearance of involuntary movements and a progressive sensory disorder that led to his transfer to the Intermediate Care Unit of the Internal Medicine Service. After laboratory tests, imaging support and evaluation by different medical specialties, the final diagnosis was a clinical picture compatible with NMDA anti-receptor encephalitis.

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.

Clinical features of Brucella meningitis combined with anti-N-methyl-D-aspartate receptor encephalitis(report of one case) / 临床神经病学杂志

Objective To investigate the clinical features of Brucella meningitis combined with anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis.Methods The clinical data of one patient diagnosed by the Department of Neurology of Nanjing Second Hospital in May 2022 with brucella meningitis combined with anti-NMDAR encephalitis were reported,and its clinical characteristics were summarized and analyzed through literature search.Results The patient was a 33-year-old man with headache,vomiting,weakness in both lower extremities,and fever 1 week later.Brain MRI showed abnormal signals in the deep white matter of the bilateral frontal lobes,and mild enhancement of the basal ganglia and pia mater.CSF suggested an increase in nucleated cells,mainly monocytes,increased protein,and decreased glucose.CSF culture showed Brucella,Brucella IgG antibody(+),Brucellosis tiger red plate agglutination test(+),test tube agglutination test was 1∶25,and temperature decreased after anti-brucella treatment.Patients presented with unresponsiveness,cognitive decline,and speech impairment in the 22nd day of the course of the disease,CSF pathogenic microorganism metagenomic testing suggested Brucella malta,and CSF autoimmune antibodies suggested moderate positivity for antiglutamate receptor(NMDAR type).Symptoms improved with high-dose shock hormone therapy.Conclusions CSF etiology metagenomic testing can improve the diagnosis rate of Brucella meningitis.Brucella may be used as a predisposing factor for anti-NMDAR encephalitis,when the patient's condition is recurrent,and cognitive decline,speech disorders and other symptoms,it is necessary to be alert to the possibility of promoting anti-NMDAR encephalitis,and relevant antibody detection should be improved in time to start immunotherapy as soon as possible.

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.

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.

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.

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.

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.

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.

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.

Research progress of anti-N-methyl-D-aspartate receptor antibody / 中华检验医学杂志

Anti-N-methyl-D-aspartate receptor (NMDAR) antibody is an autoimmune encephalitis antibody associated with Anti-NMDAR encephalitis.Since the discovery of the antibody in 2007,the basic research and clinical application of the antibody in the field of neuroimmunology have gradually increased.This article reviews the progress of anti-NMDAR antibody overview,the relationship between anti-NMDAR antibody and encephalitis,and the laboratory detection of anti-NMDAR antibody,so as to provide a reference for clinical diagnosis and treatment.

Factors Affecting the Response to First-Line Treatments in Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis

BACKGROUND AND PURPOSE: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common type of autoimmune encephalitis. This study aimed to explore the possible factors affecting the response to first-line treatments in patients with anti-NMDAR encephalitis. METHODS: We enrolled 29 patients who were diagnosed as anti-NMDAR encephalitis between January 1, 2015, and June 30, 2018. They were divided into the remission and nonremission groups according to their response to first-line treatments. The demographics, clinical manifestations, main ancillary examinations, follow-up treatments, and prognosis of patients were recorded. The symptoms reported on in this study occurred before treatments or during the course of first-line treatments. RESULTS: There were 18 patients (62.07%) in the remission group and 11 patients (37.93%) in the nonremission group. Compared to the remission group, a higher proportion of the patients in the nonremission group exhibited involuntary movements, decreased consciousness, central hypoventilation, lung infection, and hypoalbuminemia. The nonremission group had a high incidence of increased intracranial pressure and significant elevations of the neutrophil-to-lymphocyte ratio in peripheral blood (NLR), aspartate aminotransferase, and fibrinogen. Six patients (54.55%) in the nonremission group received second-line immunotherapy. Only one patient (3.45%) died, which was due to multiple-organ failure. CONCLUSIONS: Anti-NMDAR-encephalitis patients with more symptoms—especially involuntary movements, disturbance of consciousness, central hypoventilation, and accompanying hypoalbuminemia and pulmonary infection—may respond poorly to first-line treatments. Positive second-line immunotherapy therefore needs to be considered. Admission to an intensive-care unit, increased cerebrospinal fluid pressure, and increased NLR might be the significant factors affecting the response to first-line treatments.

Regard on the diagnosis and treatment of lethal Anti-NMDAR encephalitis initiated by teratoma / 中国医师杂志

Teratoma is the most common germ cell tumor,which accounts for 20％ to 40％ of ovarian tumor.Recently,teratoma has been found to be able to initiate anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis,which belongs to autoimmune encephalitis with the possibilities of lethality and disability.The main clinical features are psychosis,impaired memory,dyskinesia,autonomic dysfunction,seizures,conscious disturbance and central hypoventilation.Most patients can get a good prognosis after immunotherapy and surgery.This article reviews the progresses of anti-NMDAR encephalitis to improve the cognition of clinicians.It is recommended that all anti-NMDAR encephalitis patients should receive tumor screening.And gynecologist should pay more attention to the diagnosis and treatment of benign ovarian tumor.