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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.

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La encefalitis por virus herpes simple (VHS) es una causa frecuente de encefalitis grave y potencialmente fatal. La encefalitis autoinmune posherpética (EAPH) afecta a un porcentaje de los pacientes que han presentado encefalitis herpética (EH) y se caracteriza por la aparición de nuevos síntomas neurológico/psiquiátricos, y/o por el empeoramiento de los déficits adquiridos durante la infección viral dentro de un lapso temporal predecible. Se produce por un mecanismo no relacionado con el VHS, sino por fenómenos autoinmunes, y es susceptible de tratamiento con inmunomoduladores. Se presenta el caso de un varón de 5 años de edad con EAPH que requirió tratamiento inmunomodulador, de primera y segunda línea, con buena evolución y remisión de los síntomas.

Herpes simplex virus (HSV) encephalitis is a common cause of severe and potentially fatal encephalitis. Autoimmune post-herpes simplex encephalitis (AIPHSE) affects a percentage of patients who developed herpes simplex encephalitis (HSE) and is characterized by the onset of new neurological/psychiatric symptoms and/or worsening of deficits acquired during the herpes infection within a predictable time frame. It is caused by a mechanism not related to HSV, but by autoimmune conditions, and is susceptible to treatment with immunomodulators. Here we describe the case of a 5-year-old boy with AIPHSE who required first- and second-line immunomodulatory treatment, with an adequate course and remission of symptoms.

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Antecedentes: La encefalitis por anticuerpos contra el receptor de N-metil-D- aspartato (NMDAr), fue descrita por primera vez en 2005, y en 2007 Dalmau et al identificaron los anticuerpos contra el receptor NMDA. Se estima que anualmente hay 1.5 casos por cada millón de habitantes con mayor frecuencia en mujeres jóvenes entre 15 a 25 años, puede presentarse como un síndrome paraneoplásico asociado a teratoma ovárico en un 37%. Descripción del caso clínico: Femenina de 17 años con antecedente de teratoma de ovario izquierdo de recién diagnóstico, una semana posterior a la resección quirúrgica presenta: alucinaciones auditivas, ideación de persecución, insomnio, anhedonia, agitación psicomotriz, alteraciones del habla, discinesias orofaciales y alteraciones en la marcha, de un mes de evolución. El electroencefalograma (EEG) reportó hallazgos de disfunción cortico-subcortical severa según reporte por clínica privada sin acceso al estudio. La Resonancia Magnética (IRM) cerebral y citoquímica de líquido cefalorraquídeo (LCR) sin anormalidades. Ante sospecha clínica se inició tratamiento inmunosupresor con corticosteroides intravenosos y manejo sintomático antipsicótico, para agitación y ansiedad; inicialmente con midazolam en infusión y luego con olanzapina, risperidona y clonazepam; obteniendo una evolución clínica satisfactoria. Finalmente, se confirmó el diagnóstico al obtener un resultado positivo para IgG contra la subunidad N1 de glutamato (GluN1) del NMDAr. Conclusión: La encefalitis anti NMDAr es una condición rara y subdiagnosticada, puede confundirse con una enfermedad psiquiátrica primaria. Ante un primer episodio psicótico se debe hacer un interrogatorio y evaluación extensa, con la finalidad de descartar causas secundarias, como los trastornos autoinmunes con repercusiones neurológicas...(AU)

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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.

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Hay muchos factores implicados en la incidencia de la enfermedad de Alzheimer que, en combinación, terminan por impedir o dificultar las funciones neuronales normales. Actualmente, poco se conoce sobre la regulación del calcio, antes de la enfermedad y durante la misma. La inestabilidad interna de los niveles de calcio se asocia a un mayor riesgo vascular, condición prevalente en un gran número de individuos ya comprometidos por la enfermedad de Alzheimer. Esta revisión proporciona una reevaluación de los mecanismos moleculares de la ATPasa dependiente de Ca2+ del retículo sarcoendoplásmico (SERC-A) en la enfermedad y analiza los aspectos más destacados de la función de los canales de calcio dependientes de voltaje; de esta manera, se podrán abrir nuevas alternativas de tratamiento. Estos mecanismos de regulación son clínicamente relevantes, ya que se ha implicado la función irregular de SERC-A en diversas alteraciones de la función cerebral.

There are many factors involved in the incidence of Alzheimer's disease that, in combination, impede or hinder normal neuronal functions. Little is currently known about calcium regulation before and during the disease. Internal instability of calcium levels is associated with increased vascular risk, a prevalent condition in a high number of individuals already compromised by Alzheimer's disease. This review provides a reevaluation of the molecular mechanism of the sarcoendoplasmic reticulum calcium ATPase (SERC-A) in the disease and discusses salient aspects of voltage-gated calcium channel function; in these way new alternatives could be open for its treatment. These regulation mechanisms are clinically relevant since the irregular functions of SERC+A has been implicated in pathologies of brain function.

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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.

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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.

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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.

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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.

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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.

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La encefalitis es un desorden inflamatorio del encéfa- lo que deriva en un estado mental alterado, crisis con- vulsivas, déficits neurológicos focales, acompañado usualmente de signos de inflamación en el líquido ce- falorraquídeo y hallazgos en la resonancia magnética que pueden ir desde normalidad hasta anormalidades extensas. El anticuerpo anti RNMDA es el que origi- na la mayoría de los casos de encefalitis autoinmune en niños y adultos jóvenes, seguido por el anticuerpo anti LGI1 de presentación en el adulto. Se caracteri- zan por estar frecuentemente asociadas a algún tumor, responder a la inmunoterapia y provocar daños cere- brales variables que se manifiestan como cuadros clí- nicos polimorfos (desde la disfunción límbica hasta una encefalopatía multifocal o difusa). La prevalencia exacta de las encefalitis autoinmunes es incierta, exis- tiendo un aumento importante del reporte de casos en los últimos 10 años, asociado al avance en la pesqui- sa de los anticuerpos contra un antígeno celular espe- cífico. Todas las encefalitis autoinmunes responden a terapia inmunomoduladora, generalmente la evolución a la mejoría es lenta y puede completarse en meses o incluso en un año o más. Revisaremos generalidades de la encefalitis autoinmune, su forma más común y discutiremos su enfoque diagnóstico y tratamiento...(AU)

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RESUMEN La encefalitis asociada a anticuerpos contra el receptor de N-metil-D-Aspartato (NMDAr) es una entidad clínica recientemente descrita con un número creciente de casos reporta dos. Los síntomas psiquiátricos en etapas tempranas de la enfermedad conforman un reto diagnóstico para el médico tratante. Presentamos dos casos clínicos: el caso clínico 1, un hombre de 26 arios y el caso clínico 2, un joven de 18 arios, ambos abordados como primer episodio de psicosis y hospitalizados en instituciones psiquiátricas. Posteriormente, ambos casos fueron diagnosticados como encefalitis anti-NMDAr. La alta prevalencia de síntomas psiquiátricos en la encefalis anti-NMDAr demanda a los médicos psiquiatras y neurólogos a tener un alto índice de sospecha en presencia de síntomas atípicos en pacientes evaluados por primer episodio de psicosis.

ABSTRACT Anti-N-methyl-D-Aspartate receptor (NMDAr) encephalitis is a recently described clinical entity with an increasing number of reported cases. Psychiatric symptoms in the early stages of the disease constitute a diagnostic challenge for the treating physician. We present two clinical cases: clinical case 1, a 26-year-old man, and clinical case 2, an 18-year-old man; both presented with a first episode of psychosis and were hospitalized as psychiatric disorders. Subsequently, both cases were diagnosed as anti-NMDAr encephalitis. The high prevalence of psychiatric symptoms in anti-NMDAr encephalitis forces psychiatrists and neurologists to have a high degree of suspicion in the presence of atypical symptoms in patients evaluated for the first episode of psychosis.

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RESUMEN La encefalitis autoinmune por anticuerpos contra el receptor N-metil-D-aspartato (anti-NMDAR) es un desorden mediado por anticuerpos contra antígenos de superficie neuronal, cuyo diagnóstico temprano y tratamiento oportuno mejoran el pronóstico de la enfermedad. Se presentan cuatro casos con el diagnóstico definitivo de encefalitis autoinmune por anti-NMDAR, tratados en el Instituto Nacional de Ciencias Neurológicas en Lima-Perú. Todos los pacientes presentaron crisis epilépticas y tres casos desarrollaron un estado epiléptico refractario. Asimismo, tres pacientes presentaron alteraciones neuropsiquiátricas, discinesias y disautonomías. Dos casos requirieron soporte ventilatorio. Todos presentaron un electroencefalograma anormal, dos casos tuvieron pleocitosis en líquido cefalorraquídeo, y sólo uno mostró anormalidades cerebrales en la resonancia magnética. Respecto al tratamiento, todos los pacientes recibieron inmunoterapia con metilprednisolona y sólo dos de ellos requirieron plasmaféresis por respuesta ineficaz al tratamiento con corticoides. A los 12 meses del alta hospitalaria, tres pacientes quedaron libre de crisis epilépticas y sólo un caso no logró la independencia funcional. Estos casos muestran que la encefalitis anti-NMDAR es una condición tratable y su reconocimiento temprano junto con un tratamiento adecuado (inmunoterapia/plasmaféresis) son esenciales para una evolución favorable.

ABSTRACT Autoimmune encephalitis with antibodies against the N-methyl-D-aspartate receptor (anti-NMDAR) is a disorder mediated by antibodies against neural surface antigens, whose early diagnosis and timely treatment improve the prognosis of the disease. Four cases with the definitive diagnosis of autoimmune encephalitis by anti-NMDAR are presented, treated at the National Institute of Neurological Sciences in Lima-Peru. All patients had epileptic seizures and three cases developed a refractory epileptic state. In addition, three patients presented neuropsychiatric alterations, dyskinesias, and dysautonomia. Two cases required ventilatory support. All presented an abnormal electroencephalogram; two cases had pleocytosis in cerebrospinal fluid, and only one showed brain abnormalities on MRI. Regarding treatment, all patients received methylprednisolone immunotherapy and only two of them required plasma exchange for an ineffective response to corticosteroid treatment. After 12 months of hospital discharge, three patients were free of epileptic seizures and only one case did not achieve functional independence. These cases show that anti-NMDAR encephalitis is a treatable condition and its early recognition together with appropriate treatment (immunotherapy/plasmapheresis) are essential for a favorable evolution.

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OBJETIVOS: Relatar dois casos com apresentações diferentes de encefalite antirreceptor N-metil-D-aspartato (NMDA), uma doença autoimune recentemente identificada e caracterizada por alterações da consciência, déficit de memória, convulsões, disfunção autonômica e distúrbios do movimento. DESCRIÇÃO DOS CASOS: Criança de seis anos, sexo feminino, que se apresentou com movimentos distônicos e coreoatetósicos incapacitando a marcha. Adolescente de 17 anos, sexo masculino, com alteração do comportamento, amnésia retrógrada e convulsões. Ambos realizaram eletroencefalograma e ressonância magnética cerebral que não revelaram alterações relevantes. Os anticorpos antirreceptor NMDA foram positivos no líquido cefalorraquidiano em ambos os casos e no sangue no primeiro paciente. Foram administrados metilprednisolona, imunoglobulina e rituximab em diferentes intervalos. Ambos tiveram uma recidiva cerca de seis meses depois, com recuperação ao final de um ano e meio após o diagnóstico. CONCLUSÕES: A encefalite antirreceptor NMDA deve ser considerada quando estamos perante o início súbito de sintomas neuropsiquiátricos. O diagnóstico e terapêutica precoces são fatores prognósticos fundamentais.

AIMS: To report two cases with different presentations of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, a newly identified autoimmune disease characterized by consciousness changes, memory deficit, seizures, autonomic dysfunction and movement disorders. CASES DESCRIPTION: A six-year-old female, who presented with dystonic and choreoathetoid movements with refusal to walk. A 17-yearold male, presented with behavioral changes, retrograde amnesia and seizures. Electroencephalogram and brain magnetic resonance imaging did not show any significant findings. Anti-NMDAR antibodies were positive in cerebrospinal fluid in both cases and in serum in the first patient. Methylprednisolone, immunoglobulin and rituximab were given at different intervals. Both had a recurrence about six months later, with recovery at the end of one and a half year of the diagnosis. CONCLUSIONS: Anti-NMDAR encephalitis should be considered in patients with sudden onset of neuropsychiatric symptoms. Early diagnosis and treatment are major prognostic factors.

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ABSTRACT Autoimmune encephalitis (AIE) is one of the most common causes of noninfectious encephalitis. It can be triggered by tumors, infections, or it may be cryptogenic. The neurological manifestations can be either acute or subacute and usually develop within six weeks. There are a variety of clinical manifestations including behavioral and psychiatric symptoms, autonomic disturbances, movement disorders, and seizures. We reviewed common forms of AIE and discuss their diagnostic approach and treatment.

RESUMO As encefalites autoimunes (EAI) são a principal causa de encefalite não-infecciosa. As manifestações neurológicas são variadas, incluindo alterações comportamentais ou psiquiátricas, disautonomia, transtornos do movimento e epilepsia. Habitualmente a instalação dos sintomas ocorre em até 6 semanas, de forma aguda ou subaguda. As EAI podem ser desencadeadas por tumores, quadros infecciosos virais ou ainda apresentar etiologia criptogênica. Este artigo revisa as principais EAI, estratégias de diagnóstico e tratamento.

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ABSTRACT Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a form of autoimmune encephalopathy that presents with a wide variety of symptoms, including neuropsychiatric manifestations. The authors' aim for this study was to analyze the results of paraclinical studies of patients with a diagnosis of anti-NMDAR encephalitis and the association between symptom onset and diagnosis, and start of immunotherapy. Retrospective data of 29 patients with anti-NMDAR encephalitis were gathered and analyzed. Abnormal EEG was found in 27 patients (93.1%), whereas MRI was abnormal in 19 patients (65.5%). In contrast, an inflammatory pattern on CSF analysis was found in only 13 patients (44.8%). The absence of pleocytosis or increased proteins in the CSF was associated with a longer time from symptom onset to diagnosis and treatment (p = 0.003). The authors conclude that noninflammatory CSF may delay the correct diagnosis and start of immunotherapy in anti-NMDAR encephalitis. In the presence of suggestive clinical features, extensive studies including EEG are recommended.

RESUMEN La encefalitis por receptor anti-N-metil-D-aspartato (anti-NMDAR) es una encefalopatía autoinmune con una amplia variedad de síntomas, incluyendo manifestaciones neuropsiquiátricas. Nuestro objetivo en este estudio fue analizar los resultados paraclínicos de pacientes diagnosticados con encefalitis anti-NMDAR y la asociación entre inicio de sintomatología, el diagnóstico y el inicio de inmunoterapia. Encontramos un EEG anormal en 27 pacientes (93.1%), así como IRM anormal en 19 de ellos (65.5%). En contraste, el análisis de LCR mostró un patrón inflamatorio en tan solo 13 pacientes (44.8%). La ausencia de pleocitosis o proteínas incrementadas en el LCR se asoció con un mayor tiempo desde el inicio de la sintomatología hasta el inicio del tratamiento (p=0.003). Concluimos que el LCR no inflamatorio puede retrasar el diagnóstico correcto y el inicio de tratamiento en encefalitis anti-NMDAR, por lo que se recomienda la realización de estudios exhaustivos, incluyendo EEG, ante la presencia de indicadores clínicos sugerentes del padecimiento.

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Abstract Anti-N-methyl-D-aspartate receptor encephalitis is a recently described neurological disorder and an increasingly recognized cause of psychosis, movement disorders and autonomic dysfunction. We report 20-year-old Chinese female who presented with generalized tonic-clonic seizures, recent memory loss, visual hallucinations and abnormal behavior. Anti-N-methyl-D-aspartate receptor encephalitis was diagnosed and a computed tomography scan of abdomen reviewed a left adnexal tumor. We describe the first such case report of a patient with anti-N-methyl-D-aspartate receptor encephalitis who was given a bilateral transversus abdominis plane block as the sole anesthetic for removal of ovarian tumor. We also discuss the anesthetic issues associated with anti-N-methyl-D-aspartate receptor encephalitis. As discovery of tumor and its removal is the focus of initial treatment in this group of patients, anesthetists will encounter more such cases in the near future.

Resumo A encefalite antirreceptor de N-metil-D-aspartato (NMDA) é um distúrbio neurológico recentemente descrito e uma causa cada vez mais reconhecida de psicose, distúrbios do movimento e disfunção autonômica. Relatamos o caso de uma paciente de origem chinesa, de 20 anos, que se apresentou com crises tônico-clônicas generalizadas, perda de memória recente, alucinações visuais e comportamento anormal. Encefalite antirreceptor de NMDA foi diagnosticada e uma tomografia computadorizada de abdome revelou um tumor anexial à esquerda. Descrevemos o primeiro relato de caso de paciente com encefalite antirreceptor de NMDA submetida ao bloqueio de plano transverso abdominal (PTA) bilateral como única anestesia para remoção de tumor ovariano. Também discutimos as questões anestésicas associadas à encefalite antirreceptor de NMDA. Como a descoberta e a remoção do tumor são o foco do tratamento inicial nesse grupo de pacientes, os anestesiologistas encontrarão mais desses casos no futuro próximo.

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La encefalitis debida a anticuerpos contra receptores N-metil-D-aspartato (NMDA)es una entidad potencialmente tratable, caracterizada por síntomas neuropsiquiátricos que incluyen crisis epilépticas, alteración de conciencia, catatonía y trastornos autonómicos, y desencadenada por una respuesta inmunológica mediada por antígenos. A su vez, el síndrome DRESS (sigla en inglés de Reacción a drogas con eosinofília y síntomas sistémicos) es un cuadro de hipersensibilidad retardada mediada por células, frecuentemente asociada a fármacos antiepilépticos aromáticos. Se presenta el caso de una paciente joven que debutó con crisis epilépticas inicialmente fármaco-sensibles, desarrolló luego el síndrome de DRESS secundario a fenitoína. Cursó posteriormente con trastornos de memoria y lenguaje, alteraciones conductuales y estado catatónico y presentó anticuerpos contra receptores NMDA en el líquido cefalorraquídeo. Ambas entidades respondieron a inmunoterapia con corticoides, lo cual contribuiría a explicar una asociación fisiopatogénica entre estas dos entidades inmunomediadas.

N-Methyl-D-Aspartate receptor encephalitis is a potentially treatable entity characterized by neuropsychiatric symptoms including epileptic seizures, disruption of consciousness, catatonia, and autonomic disorders, and triggered by an immunological response mediated by an antigen. In turn, the DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a delayed cell-mediated hypersensitivity reaction, frequently associated with antiepileptic aromatic drugs. The case is presented of a young patient who debuted with epileptic seizures initially drug-sensitive, developedthen DRESS syndrome secondary to the use of phenytoin, and later presented disorders of memory and language, behavioral alterations and catatonic state, and presented anti- NMDA receptor antibodies in CSF. Both entities responded to corticoid immuno-therapy, which could contribute to explain a pathogenic association between these two immunomediated entities.

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Resumen La encefalitis por anticuerpos contra los receptores de N- Metil de aspartato (NMDA) está asociada con autoanticuerpos contra los heterómeros NR1/NR2 de los receptores de NMDA. Se presenta sobre todo en adultos jóvenes, con predominio en el sexo femenino, y buena respuesta al tratamiento. Su presentación clínica tiene manifestaciones neuropsiquiátricas, pasando por varias etapas hasta una recuperación gradual. Puede asociarse o no con la presencia de lesión tumoral Puede ser confundida fácilmente con encefalitis de tipo infecciosa por lo que es importante conocer su presentación clínica para un diagnóstico y tratamiento oportunos y así evitar mayor morbilidad y mortalidad. En este artículo se describe el caso de encefalitis autoinmune por anticuerpos contra los receptores NMDA en un hombre joven de 22 años de edad, ingresado en el Hospital Enrique Garcés de la ciudad de Quito- Ecuador y se hace una revisión de esta patología.

ABSTRACT Encephalitis caused by N-methyl-D-aspartate receptor antibodies is associated with auto antibodies against the heteromeric NR1/NR2 units of NMDA receptors. This type of encephalitis occurs more commonly in young adults, most of them women, and shows a good response to known treatments. Clinical features include neuropsychiatric manifestations, advancing through a series of stages up to a gradual recovery. This type of encephalitis can be associated with the presence, or lack thereof, lesions caused by tumors. It can easily be mistaken with infectious encephalitis, therefore is important to recognize its clinical features for an appropriate diagnosis and treatment in order to prevent higher morbidity and mortality. In this article, I describe a case study of autoimmune encephalitis caused by NMDA receptor antibodies in a twenty-two year old man, admitted to the Enrique Garcés Hospital in Quito-Ecuador, and I make a literature review on this pathology.

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Anti-N-methyl-d-aspartate receptor encephalitis is a recently described neurological disorder and an increasingly recognized cause of psychosis, movement disorders and autonomic dysfunction. We report 20-year-old Chinese female who presented with generalized tonic-clonic seizures, recent memory loss, visual hallucinations and abnormal behavior. Anti-N-methyl-d-aspartate receptor encephalitis was diagnosed and a computed tomography scan of abdomen reviewed a left adnexal tumor. We describe the first such case report of a patient with anti-N-methyl-d-aspartate receptor encephalitis who was given a bilateral transversus abdominis plane block as the sole anesthetic for removal of ovarian tumor. We also discuss the anesthetic issues associated with anti-N-methyl-d-aspartate receptor encephalitis. As discovery of tumor and its removal is the focus of initial treatment in this group of patients, anesthetists will encounter more such cases in the near future.

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