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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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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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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.

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.

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BACKGROUND: Anti-NMDAR encephalitis is an emerging differential diagnosis of first episode and persistent psychosis in the psychiatric community, as clinical manifestations include psychiatric symptoms, cognitive dysfunction, seizures, decreased consciousness, and dyskinesias. This disease is associated with extreme delta brush (EDB), but the significance and temporal course of this EEG pattern still needs to be determined. Herein, we report a case of anti-NMDAR encephalitis with persistent psychosis associated with EDB occurrence on multiple occasions during a 5-year disease course. CASE PRESENTATION: A 15-year-old girl was diagnosed with anti-NMDAR encephalitis and treated with progressive improvement. Four years after initial manifestations, an EDB pattern was seen on electroencephalogram (EEG) without new neurological symptoms. She had residual symptoms of episodic auditory hallucinations and impulsivity. One year later, the patient had a recurrence of neurological symptoms (seizures, dyskinesias and impaired attention), persisting with EDB on EEG. Clinical symptoms and EDB resolved after second-line treatment with rituximab. CONCLUSION: We describe the first case of persistent psychosis in anti-NMDAR encephalitis associated with extreme delta brush on multiple EEGs on prolonged follow-up. Electroencephalographic patterns such as EDB may serve as markers of residual disease activity, including psychiatric symptoms. Further studies with prolonged EEG monitoring are needed to better understand these findings.

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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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In recent decades, an area of active research has supported the notion that progesterone promotes a wide range of remarkable protective actions in experimental models of nervous system trauma or disease, and has also provided a strong basis for considering this steroid as a promising molecule for modulating the complex maladaptive changes that lead to neuropathic pain, especially after spinal cord injury. In this review, we intend to give the readers a brief appraisal of the main mechanisms underlying the increased excitability of the spinal circuit in the pain pathway after trauma, with particular emphasis on those mediated by the activation of resident glial cells, the subsequent release of proinflammatory cytokines and their impact on N-methyl-D-aspartate receptor function. We then summarize the available preclinical data pointing to progesterone as a valuable repurposing molecule for blocking critical cellular and molecular events that occur in the dorsal horn of the injured spinal cord and are related to the development of chronic pain. Since the treatment and management of neuropathic pain after spinal injury remains challenging, the potential therapeutic value of progesterone opens new traslational perspectives to prevent central pain.

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Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis presents commonly with psychiatric symptoms. One cohort of these patients reported that antipsychotic administration led to neuroleptic intolerance (NI) in 19% of them, which was preventable by a prompt encephalitis diagnosis. To date, there is no clear description of the "neuroleptic intolerance" spectrum in general or during anti-NMDAR encephalitis. We aimed to synthesize epidemiological and clinical characteristics of patients with NI and confirmed anti-NMDAR encephalitis, the time to the encephalitis diagnosis, the disease course, outcomes at discharge, and associated factors. We systematically searched three databases, to include clinical cases, case series, and observational studies. Additionally, we reported one clinical case. Results were summarized using narrative synthesis and the quality of the included studies was assessed. We included 22 records representing 40 patients (28 females; mean age, 24.6). Overall, the evidence quality was low. Initially, most cases were admitted in psychiatric wards (70%) with purely psychiatric symptoms (37.5%). However, most of them developed subtle concomitant neurological symptoms. The mean time to anti-NMDAR encephalitis diagnosis was 26.7 days, which was triggered by the NI in six patients. We found no association between clinical variables as delayed diagnosis, admission to psychiatric wards or the presence of malignancy with outcome variables as unfavorable outcomes at discharge, ICU, or mechanical ventilation requirement. A thorough neurological examination in young patients with new-onset psychiatric symptoms could help emergency physicians, neurologists, and psychiatrists suspect anti-NMDAR encephalitis earlier. Awareness of NI as a potential side effect during suspected or confirmed anti-NMDAR encephalitis is encouraged.

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Objective: Ketamine, an N-methyl D-aspartate (NMDA) receptor antagonist, can promote rapid action in the management of individuals with treatment-resistant depression (TRD) at sub-anesthetic doses. However, few studies have investigated the long-term use of ketamine administered intravenously (IV) and intranasally (IN). We report the design and rationale of a therapeutic trial for assessing the efficacy, safety, and tolerability of repeated-dose intramuscular (IM) ketamine vs. active treatment (escitalopram and aripiprazole) in TRD patients. Methods: A comparative, parallel-group, randomized double-blind trial assessing the efficacy, safety, and tolerability of acute (4 weeks) and maintenance (24 weeks) use of IM ketamine (0.75 mg/kg) vs. active control (escitalopram 15 mg and aripiprazole 5 mg) in individuals with moderate-severe intensity TRD (no psychotic symptoms) with or without suicide risk will be conducted. Patients with TRD (18-40 years) will be randomized and blinded to receive ketamine IM or active treatment at a 1:1 ratio for 4 weeks (active treatment) and 24 weeks (maintenance treatment). Subjects will be assessed using clinical scales, monitored for vital signs (VS) after application of injectable medication, and undergo neuropsychological tests. The primary outcome will be changed on the Montgomery-Åsberg Depression Rating Scale (MADRS) during the course of the trial. The study is in running. Results: This study can potentially yield evidence on the use of IM ketamine in the treatment of depressive disorders as an ultra-rapid low-cost therapy associated with less patient discomfort and reduced use of medical resources, and can elucidate long-term effects on different outcomes, such as neuropsychological aspects. Conclusions: The trial can help promote the introduction of a novel accessible approach for the treatment of complex disease (TRD) and also allow refinement of its long-term use. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04234776, identifier: NCT04234776.

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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

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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 SARS-CoV-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.

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.

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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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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 young women. 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

La encefalitis por anticuerpos contra el receptor N-metil-D-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.

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The spectrum of autoimmune encephalitis (AE) encompasses several entities characterized by a variable frequency of psychiatric symptoms, cognitive dysfunction, focal deficits, and seizures. Although patients with AE can be categorized in specific syndromes, overlapping manifestations are also common. Furthermore, atypical correlations between clinical phenotypes and autoantibody profiles could occur in rare cases. Here, we report the rare case of a young adult man attending due to new-onset seizures and a history of memory loss, autonomic disturbances, headache, behavioral changes, and visual and olfactory hallucinations. The patient was subjected to a complete diagnostic approach that included a comprehensive laboratory workup, neuropsychological testing, electroencephalogram, cerebrospinal fluid (CSF) analysis, brain MRI, and positron emission tomography/computed tomography scan that revealed a functional and structural compromise of the bilateral medial temporal lobes. Together with the clinical manifestations of the patient, these findings were compatible with the diagnosis of autoimmune limbic encephalitis (ALE). Strikingly, further analysis of the CSF showed autoantibodies against the N-methyl-D-aspartate (NMDA) receptor. We found very few cases of the co-occurrence of anti-NMDA receptor antibodies and nonparaneoplastic ALE in the literature, especially in male patients. Our report exemplifies the complicated differential diagnosis of ALE and adds clinical information of the association with anti-NMDA receptor antibodies.

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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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Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an immune-mediated disease that induces a wide spectrum of symptoms, especially in toddlers. These include acute-onset movement disorders, with neurological regression, and other associated neurological symptoms. Anti-NMDAR encephalitis remains a diagnostic challenge, especially in toddlers, with better prognosis associated with early treatment. We report the case of a 15-months-old boy who initially presented with vomiting and later with acute-onset dystonia after the administration of antiemetics. Within 14 days, the patient developed neuropsychomotor developmental regression and worsening dystonia. After ruling out an acute dystonic reaction and glutaric acidemia type 1 (GA-1), a final diagnosis of anti-NMDAR encephalitis was made. The patient responded well to immunomodulatory therapy. The present case underscores the importance of early treatment for patient prognosis and of including anti-NMDAR encephalitis in the differential diagnosis of acute-onset movement disorders.

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BACKGROUND: Encephalitis due to anti-N-methyl-D-aspartate receptor antibodies (ANMDARE) is the most frequent immune-mediated encephalitis. It is distinguished by the subacute onset of neuropsychiatric symptoms. OBJECTIVE: To evaluate the characteristic neuropsychiatric symptoms and their outcome in patients diagnosed with ANMDARE. METHODS: This was a prospective, longitudinal study in patients with a diagnostic suspicion of ANMDARE that presented to the National Institute of Neurology from March 2018 to February 2019. A comparative analysis of two groups (positive N-methyl-D-aspartate receptor [NMDAR] vs. negative NMDAR antibodies in cerebrospinal fluid [CSF]) was done on admission and at discharge. Neuropsychiatric systematic assessments included the Neuropsychiatric Inventory Questionnaire, the Bush Francis Catatonia Rating Scale, the Confusion Assessment Method Severity, the Montreal Cognitive Assessment, and the Overt Agitation Severity Scale. RESULTS: 24 individuals were analysed: 14 had positive NMDAR antibodies, and 10 had negative NMDAR antibodies in CSF. On admission, agitation/aggression, euphoria/exaltation, and disinhibition were more common in patients with positive antibodies. Excited catatonia and delirium were diagnosed more frequently in patients with positive antibodies. At discharge, there was an important decrease in neuropsychiatric symptoms, but substantial cognitive impairment remained. The mean hospitalisation length was 41.71 (SD 39.33) days for patients with definitive ANMDARE (p 0.259). CONCLUSIONS: Neuropsychiatric symptoms profile in ANMDARE was associated with the early onset of euphoria/exaltation and disinhibition, accompanied by marked psychomotor agitation. When ANMDARE was suspected, the presence of excited-type catatonia and delirium showed a tendency to predict definitive ANMDARE. At discharged, most patients recovered from catatonia, delirium, and psychosis, but marked cognitive symptoms, anxiety, and depression persisted at discharge.

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