Autoimmune encephalitis in a resource-limited public health setting: a case series analysis / Encefalite autoimune em um hospital universitário público: análise de uma série de casos

Abstract Background Autoimmune encephalitis (AE) consists of a group of acquired diseases that affect the central nervous system. A myriad of phenotypes may be present at the onset. Due to the heterogeneity of clinical presentations, it is difficult to achieve uniformity for the diagnostic and therapeutic processes and follow-up strategies. Objective To describe a series of patients diagnosed with AE in a resource-limited public hospital in southern Brazil and to analyze therapeutics and outcomes. Methods We retrospectively reviewed the electronic medical records of patients diagnosed with AE at the Hospital de Clínicas de Porto Alegre from 2014 to 2022. Data collected included clinical presentation, neuroimaging, cerebrospinal fluid testings, electroencephalogram, autoantibodies, treatments, outcomes, follow-up time, degree of neurological impairment, and mortality. Results Data from 17 patients were retrieved. Eleven cases were classified as definite AE and 6 as possible AE. Autoantibodies were identified in 9 patients. Timing for diagnosis was impacted by the high costs associated with autoantibody testing. Most patients became functionally dependent (82.4%) and most survivors remained with autoimmune-associated epilepsy (75%). Five patients died during hospitalization, and one after a 26-month of follow-up. Conclusion In this resource-limited hospital, patients with AE had a worse clinical outcome than that previously described in the literature. Development of epilepsy during follow-up and mortality were greater, whilst functional outcome was inferior. Autoantibody testing was initially denied in most patients, which impacted the definitive diagnosis and the use of second-line therapies.

Resumo Antecedentes A encefalite autoimune (EA) consiste em um grupo de doenças adquiridas que afetam o sistema nervoso central. Objetivo Descrever uma série de pacientes diagnosticados com EA em um contexto de atenção terciária à saúde com recursos limitados e analisar a terapêutica e os resultados. Métodos Revisamos retrospectivamente os prontuários eletrônicos de pacientes diagnosticados com EA no Hospital de Clínicas de Porto Alegre de 2014 a 2022. Os dados coletados incluíram apresentação clínica, neuroimagem, exames de líquido cefalorraquidiano, eletroencefalograma, autoanticorpos, tratamentos, resultados, tempo de acompanhamento, grau de comprometimento neurológico e mortalidade. Resultados Dados de 17 pacientes foram coletados. Onze casos foram classificados como EA definitivo e seis como EA possível. Autoanticorpos foram identificados em nove pacientes. O tempo para o diagnóstico foi afetado pelos altos custos associados ao teste de autoanticorpos. A maioria dos pacientes tornou-se funcionalmente dependente (82,4%), e a maioria dos sobreviventes permaneceu com epilepsia autoimune associada (75%). Cinco pacientes faleceram durante a internação, e um após 26 meses de seguimento. Conclusão No hospital em questão, os pacientes com EA tiveram um desfecho clínico pior do que o previamente descrito na literatura. O desenvolvimento de epilepsia durante o acompanhamento e a mortalidade foram maiores, enquanto o desfecho funcional foi inferior. Os testes de autoanticorpos foram inicialmente negados para a maioria dos pacientes, o que impactou o diagnóstico definitivo e o uso de terapias de segunda linha.

Manifestaciones neurológicas asociadas a infección por virus chikungunya en una población pediátrica hospitalaria

Introducción: La infección por Chikungunya se presenta fiebre y afectación cutánea. Las manifestaciones neurológicas, incluyen encefalopatías principalmente encefalitis; afectación periférica como mielitis, o una combinación de éstas. Objetivo: Describir la frecuencia y las manifestaciones neurológicas asociadas a infección por virus Chikungunya en el periodo enero-marzo 2023 en una población pediátrica. Materiales y Métodos: Estudio descriptivo retrospectivo de corte transversal de serie de casos Ingresaron menores de 18 años con manifestaciones neurológicas y resultados positivos PCR RT a virus Chikungunya que acudieron a un Hospital Público en enero-marzo del 2023. Las variables: demográficas, tiempo de evolución, síntomas, diagnósticos neurológicos, estudio de líquido cefalorraquídeo, electroencefalograma, estudios imagenológicos, tratamiento, ingreso a Unidad de Cuidados Intensivos, disfunción orgánica, mortalidad. Los datos se analizaron en SPSS utilizando estadística descriptiva. El protocolo fue aprobado por el comité de ética. Resultados: Ingresaron 24 pacientes, con edad de 10.0 ±1 meses. El 58.7% de sexo masculino. Como síntoma neurológico, el 54.1% tuvo convulsión. Los diagnósticos neurológicos, el 83.3% fue Encefalitis. Los pacientes con diagnóstico de Encefalitis, 75% fueron menores de 3 meses, 50% con líquido cefalorraquídeo patológico, 45% se realizó Electroencefalografía, 50% recibió inmunoglobulinas. El 50% ingresaron a Unidad de Cuidados Intensivos. Pediátricos. El 60% presentó disfunción orgánica. La mortalidad fue del 4.2%. Conclusión: El diagnóstico neurológico más frecuente fue la encefalitis, predominó en lactantes menores de 3 meses. Los síntomas neurológicos fueron: crisis convulsivas e irritabilidad. Más de la mitad presentaron disfunción orgánica, se registró la mortalidad de un paciente.

Introduction: Chikungunya infection present clinically with fever and skin involvement. Neurological manifestations include encephalopathies, mainly encephalitis and meningoencephalitis; peripheral involvement such as myelitis, Guillain Barré Syndrome; or a combination of these such as encephaloneuromyelopathy. Objective: To describe the frequency and neurological manifestations associated with Chikungunya virus infection during the January-March 2023 time period in a pediatric population. Materials and Methods: This was a descriptive, retrospective and cross-sectional study of a case series. Minors under 18 years of age were admitted with neurological manifestations and positive RT-PCR results for Chikungunya virus who presented to a Public Hospital in January-March 2023. The variables were: demographics, reason for hospitalization, symptoms, neurological diagnoses, cerebrospinal fluid study, electroencephalogram, imaging studies, treatment, admission to the Intensive Care Unit, organic dysfunction and mortality. Data were analyzed in SPSS using descriptive statistics. The protocol was approved by the Ethics Committee. Results: 24 patients were admitted, aged 10.0 ±16 months. 58.7% were male. As a neurological symptom, 54.1% had a seizure. Among the neurological diagnoses, 83.3% were encephalitis. Among the patients diagnosed with encephalitis, 75% were younger than 3 months, 50% had pathological cerebrospinal fluid, 45% underwent electroencephalography, and 50% received immunoglobulins. 50% were admitted to the Pediatric Intensive Care Unit. 60% presented organic dysfunction. Mortality was 4.2%. Conclusions: The most frequent neurological diagnosis was encephalitis, it predominated in infants under 3 months. The neurological symptoms were: seizures and irritability. More than half presented organic dysfunction, one patient expired.

Encefalitis autoinmune seronegativa asociada a síndrome de Sjögren primario / Autoimmune seronegative encephalitis associated to primary Sjögren's disease

La encefalitis autoinmune es un trastorno inmunomediado que compromete distintos territorios del parénquima cerebral, involucrando frecuentemente la materia gris profunda o la corteza, con o sin compromiso de la materia blanca, meninges o médula espinal. Se asocia frecuentemente con enfermedades autoinmunes o paraneoplásicas, y constituye un reto diagnóstico. Reportamos el caso de una mujer de 55 años con antecedente de síndrome de Sjögren que consultó a Emergencias por cefalea y confusión. El líquido cefalorraquídeo (LCR) presentaba leucocitosis con neutrofilia. En la resonancia magnética nuclear (RMN) cerebral se evidenciaron múltiples imágenes de comportamiento restrictivo, de señal hiperintensa en T2 y FLAIR, a predominio córtico-subcortical a nivel occipital bilateral, hemisferio cerebeloso derecho y parietal derecho. Se descartaron infecciones y neoplasias. El panel de anticuerpos para encefalitis autoinmune aquaporina-4 y anti-MOG en LCR fue negativo. Recibió metilprednisolona endovenosa con mejoría progresiva de los síntomas.

Autoimmune encephalitis is an immune-mediated disorder that affects different areas of the brain parenchyma, often involving deep gray matter or the cortex, with or without involvement of white matter, meninges, or spinal cord. It is frequently associated with autoimmune or paraneoplastic diseases and is a diagnostic challenge. We report the case of a 55-year-old woman with history of Sjögren's syndrome who presented to the emergency department with headache and episodes of confusion. Cerebrospinal fluid (CSF) analysis showed leukocytosis with neutrophilia. Brain MRI revealed multiple restricted diffusion lesions with hyperintense signal on T2 and FLAIR sequences, predominantly in the bilateral occipital region, right cerebellar hemisphere, and right parietal region. Infections and neoplasms were ruled out. The panel of antibodies for autoimmune encephalitis, including Aquaporin-4 and anti-MOG in CSF, was negative. She received intravenous methylprednisolone, leading to symptom improvement.

Encefalitis autoinmune posherpética. Caso clínico pediátrico / Autoimmune post-herpes simplex encephalitis. A pediatric clinical case report

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.

Review of dengue, zika and chikungunya infections in nervous system in endemic areas / Revisão da infecção por dengue, zika e chikungunya no sistema nervoso em áreas endêmicas

Abstract Dengue, zika, and chikungunya are arboviruses of great epidemiological relevance worldwide. The emergence and re-emergence of viral infections transmitted by mosquitoes constitute a serious human public health problem. The neurological manifestations caused by these viruses have a high potential for death or sequelae. The complications that occur in the nervous system associated with arboviruses can be a challenge for diagnosis and treatment. In endemic areas, suspected cases should include acute encephalitis, myelitis, encephalomyelitis, polyradiculoneuritis, and/or other syndromes of the central or peripheral nervous system, in the absence of a known explanation. The confirmation diagnosis is based on viral (isolation or RT-PCR) or antigens detection in tissues, blood, cerebrospinal fluid, or other body fluids, increase in IgG antibody titers between paired serum samples, specific IgM antibody in cerebrospinal fluid and serological conversion to IgM between paired serum samples (non-reactive in the acute phase and reactive in the convalescent). The cerebrospinal fluid examination can demonstrate: 1. etiological agent; 2. inflammatory reaction or protein-cytological dissociation depending on the neurological condition; 3. specific IgM, 4. intrathecal synthesis of specific IgG (dengue and chikungunya); 5. exclusion of other infectious agents. The treatment of neurological complications aims to improve the symptoms, while the vaccine represents the great hope for the control and prevention of neuroinvasive arboviruses. This narrative review summarizes the updated epidemiology, general features, neuropathogenesis, and neurological manifestations associated with dengue, zika, and chikungunya infection.

Resumo Dengue, zika e chikungunya são arboviroses de grande relevância epidemiológica em todo o mundo. A emergência e reemergência dessas infecções virais transmitidas por mosquitos constituem um grave problema de saúde pública humana. As manifestações neurológicas causadas por esses vírus têm alto potencial de morte ou sequelas. As complicações que ocorrem no sistema nervoso associadas às arboviroses podem representar um desafio diagnóstico e de tratamento. Em áreas endêmicas, casos suspeitos devem incluir encefalite, mielite, encefalomielite, polirradiculoneurite e/ou outras síndromes do sistema nervoso central ou periférico, na ausência de explicação conhecida. Caso confirmado de arbovirose neuroinvasivo é baseado na detecção viral (isolamento ou RT-PCR) ou de antígenos em tecidos, sangue, líquido cefalorraquidiano ou outros fluidos corporais, aumento dos títulos de anticorpos IgG entre amostras de soro pareadas, anticorpo IgM específico no líquido cefalorraquidiano e conversão sorológica para IgM entre amostras de soro pareadas. O exame do líquido cefalorraquidiano pode demonstrar: 1. agente etiológico; 2. reação inflamatória ou dissociação proteico-citológica, dependendo do quadro neurológico; 3. valor absoluto de IgM específica; 4. síntese intratecal de anticorpos IgG específicos (dengue e chikungunya); 5. exclusão de outros agentes infecciosos. O tratamento das complicações neurológicas visa melhorar os sintomas, enquanto a vacina representa a grande esperança para o controle e a prevenção das arboviroses neuroinvasivas. Esta revisão narrativa resume a atualização da epidemiologia, características gerais, neuropatogênese e manifestações neurológicas associadas à infecção pelos vírus da dengue, zika e chikungunya.

Encefalitis asociada a infección por SARS-CoV-2

El virus SARS-CoV-2 produce una enfermedad conocida como COVID-19 y puede producir complicaciones neurológicas como la encefalitis, la cual consiste en la inflamación a nivel del parénquima cerebral. Su pronto diagnóstico es crucial para poder asegurar la supervivencia de los individuos, ya que puede llevar al paciente al ingreso en unidad de cuidados intensivos. El tratamiento consiste en el soporte vital, la disminución de la inflamación y de la presión intracraneal, aunque estas medidas en ocasiones no son suficientes debido a que posee una alta tasa de mortalidad. Objetivo. Identificar las principales características clínicas de la encefalitis asociada a la infección por SARS-CoV-2. Metodología. Se realizó una revisión sistemática bajo la metodología PRISMA, utilizando diversos motores de búsqueda como PubMed, ScienceDirect, Web of Science y Scopus de los últimos cinco años en idioma inglés y español. Resultados. Se encontraron 63 artículos identificados en las bases de datos: PubMed; 18, Scielo con un total de 3, Sciencedirect con 3 y Google Scholar; 39. De estos artículos encontrados, 15 artículos estaban duplicados, 13 artículos eliminados por título y resumen, esto realizado luego de tomar en cuenta criterios de exclusión y relevancia del artículo mismo, se eliminaron 25 artículos luego de analizar el texto completo, obteniendo finalmente 10 artículos a emplear dentro del presente estudio. Conclusión. Se concluyó que el SARS-CoV-2 tiene repercusión a nivel del sistema nervioso central, dando como resultado la presencia de patologías como encefalitis, la cual tiene una baja incidencia entre los pacientes, pero una mortalidad para nada despreciable.

The SARS-CoV-2 virus produces a disease known as COVID-19 and can produce neurological complications such as encephalitis, which consists of inflammation at the level of the brain parenchyma. Early diagnosis is crucial to ensure the survival of individuals, as it can lead to admission to the intensive care unit. Treatment consists of life support, reduction of inflammation and intracranial pressure, although these measures are sometimes not sufficient due to a high mortality rate. Objective. To identify the main clinical features of encephalitis associated with SARS-CoV-2 infection. Methodology. A systematic review was carried out under the PRISMA methodology, using different search engines such as PubMed, ScienceDirect, Web of Science and Scopus from the last five years in English and Spanish. Results. We found 63 articles identified in the databases: PubMed; 18, Scielo with a total of 3, Sciencedirect with 3 and Google Scholar; 39. Of these articles found, 15 articles were duplicates, 13 articles eliminated by title and abstract, this done after taking into account exclusion criteria and relevance of the article itself, 25 articles were eliminated after analyzing the full text, finally obtaining 10 articles to be used within the present study. Conclusion. It was concluded that SARS-CoV-2 has repercussions at the level of the central nervous system, resulting in the presence of pathologies such as encephalitis, which has a low incidence among patients, but not negligible mortality.

O vírus SARS-CoV-2 causas uma doença conhecida como COVID-19 e pode levar a complicações neurológicas, como a encefalite, que consiste em uma inflamação no nível do parênquima cerebral. O diagnóstico precoce é fundamental para garantir a sobrevivência dos indivíduos, pois pode levar à internação na unidade de terapia intensiva. O tratamento consiste em suporte à vida, redução da inflamação e redução da pressão intracraniana, embora essas medidas às vezes não sejam suficientes devido à alta taxa de mortalidade. Objetivo. Identificar as principais características clínicas da encefalite associada à infecção pelo SARS-CoV-2. Metodologia. Foi realizada uma revisão sistemática de acordo com a metodologia PRISMA, usando vários mecanismos de busca, como PubMed, ScienceDirect, Web of Science e Scopus, dos últimos cinco anos, em inglês e espanhol. Resultados. Sessenta e três artigos foram identificados nos seguintes bancos de dados: PubMed; 18, Scielo com um total de 3, Sciencedirect com 3 e Google Scholar; 39. Desses artigos encontrados, 15 eram duplicatas, 13 artigos foram eliminados pelo título e resumo, o que foi feito após levar em conta os critérios de exclusão e a relevância do artigo em si, 25 artigos foram eliminados após a análise do texto completo, obtendo-se finalmente 10 artigos a serem usados no presente estudo. Conclusões. Concluiu-se que o SARS-CoV-2 tem repercussões em nível do sistema nervoso central, resultando na presença de patologias como a encefalite, que tem baixa incidência entre os pacientes, mas mortalidade não desprezível.

Secuelas cognitivas en encefalitis inmunomediadas: cohorte de pacientes en Argentina / Cognitive sequelae in immunomediated encephalitis: cohort of patients in Argentina

Resumen Introducción: Las encefalitis inmunomediadas son un desorden neurológico de origen autoinmune. Actual mente es escasa la descripción de las secuelas cognitivas crónicas. El objetivo del presente trabajo fue caracterizar la secuela cognitiva de diferentes tipos de encefalitis inmunomediadas en una cohorte de un centro único de Argentina. Métodos: Estudio prospectivo, observacional, trans versal, de pacientes en seguimiento en un hospital de la Ciudad de Buenos Aires, con diagnóstico de encefalitis inmunomediada probable y definitiva. Se evaluaron variables epidemiológicas, clínicas, paraclínicas y tra tamiento. Se determinó la secuela cognitiva a través de una evaluación neurocognitiva realizada a partir del año de la presentación clínica. Resultados: Fueron incluidos 15 pacientes, todos con resultado disminuido en al menos un test. La memoria fue el dominio más afectado. Aquellos que se encon traban bajo tratamiento inmunosupresor al momento de evaluarse presentaron menores resultados en el aprendizaje seriado (media -2.94; desvío estándar 1.54) versus los que se encontraban sin tratamiento (media -1.18; desvío estándar 1.40; p = 0.05) y en la prueba de reconocimiento (media -10.34; desvío estándar 8.02) ver sus sin tratamiento (media -1.39; desvío estándar 2.21; p = 0.003). Los pacientes con estatus epiléptico tuvieron resultados deficitarios en la prueba de reconocimiento (media -7.2; desvío estándar 7.91) en comparación a los que no lo tenían (media -1.47; desvío estándar 2.34; p = 0.05). Conclusión: Nuestros resultados demuestran que, a pesar del curso monofásico de la enfermedad, todos los pacientes presentan daño cognitivo persistente más allá del año del inicio del cuadro. Estudios prospectivos de mayor envergadura serían necesarios para confirmar nuestros hallazgos.

Abstract Introduction: Autoimmune encephalitis represents a group of immune-mediated neurological disorders. At present, the description of the chronic cognitive sequela is scarce. The objective of this study was to characterize the cognitive after effects of different types of autoimmune encephalitis in a cohort from a single center in Argentina. Methods: Prospective, observational, cross-sectional study of patients under follow-up at a hospital in Buenos Aires city, with a diagnosis of probable and definitive immune-mediated encephalitis. Epidemiological, clini cal, paraclinical and treatment related variables were evaluated. Cognitive sequela was determined through a neurocognitive evaluation performed at least a year after the clinical presentation. Results: Fifteen patients were included. All had di minished results in at least one test. Memory was the most affected domain. Patients who were under im munosuppressive treatment at the time of evaluation presented lower results in serial learning (mean -2.94; standard deviation 1.54) versus those who weren't under treatment (mean -1.18; standard deviation 1.40; p = 0.05). The same pattern was observed on the recognition test of treatment group (mean -10.34; standard deviation 8.02) versus treatment-free group (mean -1.39; standard deviation 2.21; p =0.003). Patients with status epilepticus had poorer results in the recognition test (mean -7.2; standard deviation 7.91) compared to those without it (mean -1.47; standard deviation 2.34; p = 0.05). Conclusion: Our results show that, despite the mo nophasic course of this disease, all patients had persis tent cognitive damage beyond the year of onset. Larger prospective studies are required to confirm our findings.

Autoimmune encephalitis related to nivolumab followed by tumor regression / Encefalitis autoinmune relacionada con nivolumab se guida de regresión tumoral

Abstract Immune checkpoints inhibitors have shown a re markable improvement in overall survival of stage IV renal cell carcinoma patients. Nevertheless, there is a wide range of immune-related adverse events (IRAE) that arise from these revolutionary treatments. Autoim mune encephalitis is a rare but severe central nervous system IRAE in these cancer patients. The severities of these IRAEs preclude patients from continuing im munotherapy treatment. Few cases of autoimmune encephalitis with immunotherapy have been described in the literature and optimal clinical management of these events as well as patient's immune-mediated response after treatment suspension is still unclear. Here, we report a case of a 67 years-old woman with stage IV renal cell carcinoma under treatment with nivolumab who developed autoimmune encephalitis. After high doses of corticosteroids patient's condition improved significantly with full recovery after 5 days of treatment. Even though nivolumab was not reinstalled, a persistent response of her oncologic disease was evi denced. We expect that this case can contribute to the existing literature of both subjects, the management of autoimmune encephalitis as grade IV immune related adverse event and the responses of immune checkpoint inhibitors after IRAE.

Resumen Los inhibidores de puntos de control inmunológico han mostrado una importante mejoría en la supervi vencia global de los pacientes con carcinoma de riñón estadio IV. Sin embargo, existe una amplia variedad de efectos adversos inmunomediados que surgen a partir de estos tratamientos revolucionarios. La encefalitis au toinmune es un infrecuente pero grave efecto adverso inmunomediado del sistema nervioso central en estos pacientes. La gravedad de este cuadro impide que los pa cientes continúen con el tratamiento de inmunoterapia. Se han descrito pocos casos de encefalitis autoinmune con inmunoterapia en la literatura y aún no está claro el manejo clínico óptimo de estos eventos, ni cómo continua la respuesta inmunomediada después de la suspensión del tratamiento. Presentamos el caso de una mujer de 67 años con carcinoma de células renales estadio IV que desarrolló encefalitis autoinmune durante el tratamiento con nivolumab. La paciente mejoró significativamente luego del inicio del tratamiento con altas dosis de cor ticoides, con una recuperación completa después de 5 días del mismo. Si bien el nivolumab no se reinició, se evidenció una respuesta persistente de su enfermedad oncológica. Esperamos que este caso pueda contribuir a la literatura existente de ambos temas, el manejo de la encefalitis autoinmune como efecto adverso inmunome diado grado IV y las respuestas que se obtienen con la inmunoterapia luego de estos efectos adversos.

Encefalitis aguda por dengue durante el embarazo

El dengue es un problema de salud pública. La mayoría de los pacientes desarrollan signos clínicos que van desde enfermedad leve hasta síndrome hemorrágico. Las manifestaciones neurológicas inusuales son raras y cada vez existen más pruebas de neurotropismo. La encefalitis por dengue es el resultado del trastorno multisistémico que ocurre en la infección grave y durante el embarazo puede ser difícil de diagnosticar. Además, es importante considerarla como diagnóstico diferencial en pacientes en zonas endémicas en pacientes con enfermedad febril aguda y síntomas neurológicos. El manejo de la encefalitis por dengue durante el embarazo es un desafío y es necesario realizar todas las pruebas posibles para decidir el manejo óptimo y preciso para evitar complicaciones maternas. Se presenta un caso de encefalitis aguda por dengue durante el embarazo.

Dengue is a public health problem. Most patients develop clinical signs ranging from mild illness to hemorrhagic syndrome. Unusual neurological manifestations are rare and there is increasing evidence of neurotropism by the virus. Dengue encephalitis is the result of the multisystem disorder that occurs in severe infection and during pregnancy can be difficult to diagnose. In addition, it is important to consider it as a differential diagnosis in patients in endemic areas in patients with acute febrile illness and neurological symptoms. The management of dengue encephalitis during pregnancy is a challenge and it is necessary to perform all possible tests to decide the optimal and accurate management to avoid maternal complications. A case of acute dengue encephalitis during pregnancy is presented.

Epilepsia secundaria a encefalitis por el virus de Epstein Barr / Epilepsy secondary to encephalitis due to Epstein Barr virus

Presentación del caso. Se trata de una mujer de 44 años de edad, con historia de cefalea occipital, lenguaje incoherente y pensamiento confuso. Inicialmente presentaba diez puntos en la escala de Glasgow y una hemiparesia izquierda. La tomografía computarizada de cráneo, reportó edema cerebral con lesión hipodensa talámica derecha y deterioro neurológico progresivo.El electroencefalograma evidenció desaceleración unilateral hemisférica derecha. El estudio del líquido cefalorraquídeo describió hiperproteinorraquia y un recuento a predominio linfocitario de 450 células con glucorraquia conservada, sin presencia de bacterias. Intervención terapéutica. se manejó con soporte ventilatorio invasivo y con tratamiento antibiótico y antiviral a dosis meníngeas, además de anticonvulsivantes. Los hallazgos tomográficos de control reportaron una hidrocefalia; se colocó una derivación ventricular tipo Becker. La serología IgM resultó positiva para virus de Epstein Barr y se identificó el genoma viral en el líquido cefalorraquídeo, a través de la prueba de reacción en cadena de polimerasa. La tomografía cerebral de control, evidenció la persistencia de la ventriculomegalia y de edema cerebral, lo que generó el diagnóstico de una encefalitis de etiología viral complicada con epilepsia secundaria por una lesión estructural desmielinizante del hemisferio cerebral derecho. Evolución clínica. La intervención terapéutica con inmunoglobulina intravenosa generó una mejoría del estado general. Fue posible retirar la derivación ventricular y la ventilación pulmonar diez y 19 días después del ingreso, respectivamente. La paciente se encuentra actualmente en fisioterapia con persistencia de hemiparesia izquierda, alteraciones de la marcha, disartria y episodios convulsivos controlados durante los últimos seis meses

Case presentation. This case is about a 44 years old woman with a history of occipital headache, incoherent speech and confused thinking. She initially presented ten points on the Glasgow scale and left hemiparesis. Cranial CT scan reported cerebral edema with right thalamic hypodense lesion and progressive neurological deterioration. The electroencephalogram showed unilateral right hemispheric deceleration. The cerebrospinal fluid study showed hyperproteinuria and a predominantly lymphocyte count of 450 cells with preserved glycorrhachia, without the presence of bacteria. Treatment.was managed with invasive ventilatory support and antibiotic and antiviral treatment at meningeal doses, in addition to anticonvulsants. Control tomographic findings showed hydrocephalus; a Becker type ventricular shunt was placed. IgM serology was positive for Epstein Barr virus and the viral genome was identified in the cerebrospinal fluid by polymerase chain reaction test. The control brain tomography showed persistent ventriculomegaly and cerebral edema, which led to the diagnosis of encephalitis of viral etiology complicated by epilepsy secondary to a demyelinating structural lesion of the right cerebral hemisphere. Outcome. Therapeutic intervention with intravenous immunoglobulin was performed with improvement of the general condition, it was possible to remove the ventricular shunt and pulmonary ventilation ten and 19 days after admission, respectively. The patient is currently in physical therapy with persistence of left hemiparesis, gait disturbances, dysarthria, and controlled convulsive episodes during the last six months.

DIAGNOSTIC DILEMMA IN TYPHOID ENCEPHALOPATHY

Using the immune system to its advantage, Salmonella Typhi initially invades the gut followed by the reticuloendothelial system and finally the nervous system, involvement of which usually occurs around the second week of fever. In developing countries, delayed diagnosis is predominantly due to hesitation in seeking treatment. Our subject presented with fever since one week, altered mentation, headache and neck pain; she was diagnosed with enteric fever. Although her neurological abnormality could be a complication of the infection, it appeared when she became afebrile- hence we evaluated her for autoimmune conditions. Positive results hinted at autoimmune encephalitis triggered by the infection; further studies were inconclusive. Association of enteric fever with autoimmune encephalitis has not been reported. Three months later, presence of antinuclear antibodies (ANA) was rechecked- a negative report led to a retrospective diagnosis of transient ANA positivity in a nonautoimmune inflammatory disease, the case in point being enteric fever.

The relationship between MMP-2 rs243865, MMP-9 rs398242 and CXCL-12 rs1801157 gene polymorphisms with Japanese encephalitis disease and disease outcome in North Indian population

Background & objectives: Japanese encephalitis virus (JEV) is one of the most important causes of acute and uncontrolled inflammatory disease in Asia. Matrix metalloproteinases (MMPs) and chemokines play a detrimental role in the host response to JE disease, aetiology, and disease outcome. Evidently, MMPs are widely circulated in the brain and regulate various process including microglial activation, inflammation, blood-brain barrier disruption as well as affects central nervous system (CNS). The present study was to assess the association of single nucleotide polymorphisms of MMP-2, MMP-9 and chemokine (CXCL-12/SDF1-3’) in the north Indian population. Methods: We performed case-control study comprising of 125 patients and 125 healthy controls in north Indian population. Genomic DNA was extracted from whole blood and gene polymorphism have been determined by PCR-RFLP method. Results: MMP-2, MMP-9 and CXCL-12 gene was not significantly associated with JE disease, but homozygous (T/T) genotype of MMP-2 was statically associated with disease outcome (p=0.05, OR=0.110). A/G and G/G genotype of CXCL-12 was significantly associated with severity of disease. (p=0.032, OR=5.500, p=0.037, OR= 9.167). The serum level of MMP-2 was observed significantly increased in JE patients with homozygous (T/T) genotype whereas increased MMP-9 level was associated with heterozygous genotype. Interpretation & conclusion: MMP-2, MMP-9 and CXCL-12 gene polymorphism were not associated with JE susceptibility, but MMP-2 may be contributed to disease protection. CXCL-12 was associated with disease severity. In our concern this is the first report from northern India.

Anti-CASPR2 antibody-associated autoimmune encephalitis： a case report / 四川精神卫生

This paper elaborated a case of an elderly patient with anti-contactin-associated protein-like 2 （CASPR2） antibody-associated autoimmune encephalitis. It illustrated the common manifestations and diagnostic process of anti-CASPR2 antibody-associated encephalitis， and the analysis of clinical symptoms and ancillary findings had contributed to gaining insight into the diagnosis of autoimmune encephalitis in elderly patients characterized by distinct psycho-behavioral abnormalities and cognitive decline， as well as suggesting the possibility that autoimmune encephalitis in elderly may exacerbate the development of cerebrovascular disease.

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.

Clinical features of autoimmune encephalitis secondary to epidemic encephalitis B in 5 children / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features of children with autoimmune encephalitis (AE) secondary to epidemic encephalitis B (EEB).@*METHODS@#A retrospective analysis was performed on the medical data of five children with EEB with "bipolar course" who were treated in Children's Hospital Affiliated to Zhengzhou University from January 2020 to June 2022.@*RESULTS@#Among the five children, there were three boys and two girls, with a median age of onset of 7 years (range 3 years 9 months to 12 years) and a median time of 32 (range 25-37) days from the onset of EEB to the appearance of AE symptoms. The main symptoms in the AE stage included dyskinesia (5/5), low-grade fever (4/5), mental and behavioral disorders (4/5), convulsion (2/5), severe disturbance of consciousness (2/5), and limb weakness (1/5). Compared with the results of cranial MRI in the acute phase of EEB, the lesions were enlarged in 3 children and unchanged in 2 children showed on cranial MRI in the AE stage. In the AE stage, four children were positive for anti-N-methyl-D-aspartate receptor antibody (one was also positive for anti-γ-aminobutyric acid type B receptor antibody), and one was negative for all AE antibodies. All five children in the AE stage responded to immunotherapy and were followed up for 3 months, among whom one almost recovered and four still had neurological dysfunction.@*CONCLUSIONS@#EEB can induce AE, with anti-N-methyl-D-aspartate receptor encephalitis as the most common disease. The symptoms in the AE stage are similar to those of classical anti-N-methyl-D-aspartate receptor encephalitis. Immunotherapy is effective for children with AE secondary to EEB, and the prognosis might be related to neurological dysfunction in the acute phase of EEB.

Clinical features of autoimmune glial fibrillary acidic protein astrocytopathy in children: an analysis of 34 cases / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features of children with autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A).@*METHODS@#A retrospective analysis was performed on the medical data of 34 children with GFAP-A who attended the Department of Neurology, Children's Hospital of Chongqing Medical University, from January 2020 to February 2022. The medical data included clinical manifestations, cerebrospinal fluid features, imaging examination results, treatment, and prognosis.@*RESULTS@#The median age of onset was 8.4 (range 1.9-14.9) years for the 34 children with GFAP-A. The main clinical manifestations included headache (50%, 17/34), fever (47%, 16/34), visual impairment (47%, 16/34), and disturbance of consciousness (44%, 15/34). Abnormal cerebrospinal fluid results were observed in 19 children (56%, 19/34), among whom 8 children had positive autoantibody. The children with overlap syndrome had significantly higher recurrence rate and rate of use of immunosuppressant than those without overlap syndrome (P<0.05). About 77% (24/31) of the children had good response to immunotherapy, and only 1 child had poor prognosis.@*CONCLUSIONS@#Children with GFAP-A often have non-specific clinical symptoms and show good response to immunotherapy. Children with overlap syndrome have a high recurrence rate, and early application of immunosuppressants may help to prevent recurrence and alleviate symptoms.

Espectro clínico de la Encefalitis Autoinmune no NMDAR en pediatría

En este trabajo se realizó una revisión narrativa de los principales hallazgos en la literatura médica sobre las manifestaciones clínicas de la encefalitis autoinmune pediátrica (EAP) no mediada por anticuerpos anti receptor del ácido N-metil-D-aspartato (NMDAR). Las EAP que se destacaron se asocian con anticuerpos específicos como el complejo de canales de potasio dependiente de voltaje, la decarboxilasa del ácido glutámico, el receptor del ácido alfa-amino-3-hidroxi-5-metil-4-isoxazolpropiónico y el receptor ácido-gamma-aminobutírico. El diagnóstico de esta patología es un desafío en pediatría debido a la complejidad de las manifestaciones psiquiátricas y neurológicas generadas por la afectación de la corteza, el sistema límbico, el tallo cerebral, los ganglios basales y el cerebelo. A su vez, la comprensión de sus síntomas permite identificar la superposición en las presentaciones clínicas entre los diferentes tipos de EAP y el diagnóstico diferencial con otras enfermedades inflamatorias del cerebro, infecciones, enfermedades metabólicas y trastornos psiquiátricos. El conocimiento biomédico y la sospecha clínica de las EAP no NMDAR establece un campo de investigación que crece en neuropsiquiatría y favorece el diagnóstico y tratamiento de las encefalitis subdiagnosticadas.

This work presents a narrative review of the main findings in the medical literature on the clinical manifestations of pediatric autoimmune encephalitis (PAE) not mediated by anti-N-methyl-Daspartate acid receptor (NMDAR) antibodies. Prominent PAEs are associated with specific antibodies, such as the voltage-gated potassium channel complex, glutamic acid decarboxylase, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, and alpha-amino -3-hydroxy-5. -methyl-4-isoxazolepropionic acid receptor. -gamma-aminobutyric. Diagnosis of this pathology is a challenge in pediatrics due to the complexity of psychiatric and neurological manifestations generated by involvement of cortex, limbic system, brainstem, basal ganglia and cerebellum. In turn, understanding its symptoms allows identifying the overlap in clinical presentations between the different types of PAE and the differential diagnosis with other inflammatory diseases of the brain, infections, metabolic diseases and psychiatric disorders. Biomedical knowledge and clinical suspicion of non-NMDAR PAE establishes a growing field of research in neuropsychiatry and favors the diagnosis and treatment of underdiagnosed encephalitides.

Anticuerpos Anti-Titina en Encefalitis Autoinmune: ¿Casualidad o Causalidad? A propósito de un caso

Las encefalitis autoinmunes son una condición emergente, caracterizada por la aparición repentina de síntomas psicóticos o depresivos "de novo", crisis convulsivas o estatus epiléptico refractario, o demencia rápidamente progresiva. Las encefalitis autoinmunes están asociadas a diversos fenómenos desencadenantes, como infecciones virales previas entre las más comunes, y se asocian con la presencia de anticuerpos antineuronales y/o onconeuronales, que deben estudiarse ante la sospecha de esta entidad. Es muy importante desarrollar un diagnóstico presuntivo y precoz, ya que la terapia con inmunosupresores como los corticoides -iniciados en el momento oportuno-, puede cambiar su evolución hacia la mejoría clínica. Presentamos un paciente con encefalitis autoinmunes y anticuerpos anti-Titina positivos (habitualmente presentes en timoma y miastenia gravis), no asociados a neoplasia conocida y con buena respuesta a esteroides.

Autoimmune Encephalitis, are an emerging condition, characterized by the sudden onset of psychotic or depressive symptoms "de novo", refractory seizures or epilepsy, or rapidly progressive dementias. The autoimmune encephalitis are associated to various triggered phenomena as a previous viral infections among others; it's related to the presence of antineuronal and/or onconeuronal antibodies, and there must be studied when autoimmune encephalitis is suspected. It is very important to develop a presumptive and early diagnosis, since steroid therapy -on opportunity time- can change its evolution towards clinical improvement. We present a patient with autoimmune encephalitis, and positive anti-Titin antibodies (usually presents in thymoma and myasthenia gravis) not associated with known neoplasia, and with a good response to steroids.

Encefalitis límbica asociada a secreción inadecuada de hormona antidiurética. Reporte de un caso y revisión de la literatura / Limbic encephalitis associated with inappropriate secretion of antidiuretic hormone. A case report and literature review / Encefalite límbica associada à secreção inapropriada de hormônio antidiurético. Relato de caso e revisão da literatura

La encefalitis límbica (EL) autoinmune es una afección neurológica infrecuente de curso subagudo con manifestaciones neuropsicológicas. Actualmente el tratamiento inmunoterápico agudo o de mantenimiento es dirigido según el anticuerpo neural acompañante y la presencia o ausencia de cáncer. Presentamos el caso de una mujer de 52 años con hipotiroidismo autoinmune, síndrome de secreción inadecuada de hormona antidiurética (SIADH) e hiponatremia (hipoNa) persistente, con evolución progresiva de perdida de la memoria y crisis distónicas faciobraquiales (DFBC) a quien se le realiza un diagnóstico oportuno de encefalitis límbica. Recibió tratamiento intravenoso combinado en base a corticoides e inmunoglobulina con buena respuesta y morbilidad mínima neuropsicológica. El reconocimiento de esta patología permite un diagnóstico y tratamiento temprano, imprescindible para mejorar el pronóstico de estos pacientes.

Autoimmune limbic encephalitis is a rather unusual neurological condition with subacute progression and neuropsychological symptoms. Currently, acute or maintenance treatment with immunotherapy is targeted depending on the accompanying neural specific antibody and the presence or absence of cancer. The study presents the case of a 52-year-old woman suffering from autoimmune hypothyroidism, syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) and persistent hyponatremia, with progressive evolution which involved memory loss and faciobrachial dystonic seizures (FBDS). She was timely diagnosed with limbic encephalitis and was treated with intravenous combined corticosteroids and immunoglobulin therapy. Response was good, with minimum neuropsychological. Recognizing this condition allows for early diagnosis and treatment, what is key to improve the prognosis of these patients.

A encefalite límbica (LE) autoimune é uma condição neurológica rara de curso subagudo com manifestações neuropsiquiátrica. Atualmente, o tratamento com imunoterapia aguda ou de manutenção é orientado de acordo com o anticorpo neural e a presença ou ausência de câncer. Apresentamos o caso de uma mulher de 52 anos com hipotireoidismo autoimune, síndrome de secreção inapropriada de hormônio antidiurético e hiponatremia persistente, com evolução progressiva da perda de memória e crises distônicas faciobraquiais que foi diagnosticada oportunamente como encefalite límbica. Recebeu tratamento endovenoso combinado à base de corticoide e imunoglobulina com boa resposta e morbidade neuropsiquiátrica mínima. O reconhecimento desta patologia permite um diagnóstico e tratamento precoces, essenciais para melhorar o prognóstico desses pacientes.

Clinical efficacy and influencing factors of mild therapeutic hypothermia for influenza-associated encephalopathy/encephalitis in children with different center temperatures / 中国热带医学

@#Abstract: Objective To investigate the clinical outcomes and influencing factors of mild therapeutic hypothermia for influenza-associated encephalopathy/encephalitis (IAE) in children with different center temperatures, and to provide ideas and references for new mild therapeutic hypothermia scheme. Methods　A total of 115 hospitalized children with IAE who were scheduled to receive mild therapeutic hypothermia in Zhongshan Hospital Affiliated to Xiamen University from January 2019 to February 2022 were collected as subjects. They were randomly divided into two groups, namely, the 33 ℃ group (n=60) and the 35 ℃ group (n=55). The clinical features and clinical outcomes of the two groups were analyzed. Univariate and multivariate logistic regression analysis was performed for 6-month to investigate the factors affecting neurological disability. Results　The baseline indicators after treatment, such as Glasgow Coma Scale (GCS) score, cerebrospinal fluid total protein (CSF-TP), CSF lactate dehydrogenase (CSF-LDH), lymphocyte (Lym), creatine kinase-MB (CK-MB), LDH, and neuron-specific enolase (NSE), revealed no significant differences between the two groups before treatment or after treatment (P>0.05). There was no significant difference between the two groups after treatment in the clinical outcomes including GCS score D-value, time of hospitalization, 6-month neurological disability rate and mRS score, CSF-TP D-value, CSF-LDH D-value, Lym D-value, CK-MB D-value, LDH D-value, NSE D-value, improvement rate of EEG and MRI (P>0.05). Univariate and multivariate logistic regression analyses [OR=1.185, 95%CI (1.026~1.369), P=0.021] indicated that the delay of the onset of mild therapeutic hypothermia treatment was an independent risk factor for neurological disability in children with IAE after mild therapeutic hypothermia treatment of 6 months. Conclusion　There was no significant difference in the clinical outcomes between 33 ℃ and 35 ℃ mild therapeutic hypothermia for children with IAE. Therefore, mild therapeutic hypothermia for children with IAE may not require a strict requirement. Timely receipt of mild therapeutic hypothermia is a key measrue to reduce the risk of neurological disability in children with IAE.