Tratamiento y evolución de la encefalitis inmunomediada en edad pediátrica, serie de casos / Treatment and outcome of immune-mediated encephalitis in children, a case series

Introducción: La encefalitis por anticuerpos contra el receptor N-metil.D.aspartato (NMDA-R) es un trastorno inflamatorio del sistema nervioso central (SNC) en el cual autoanticuerpos dirigidos hacia la subunidad NR1 del receptor N-metil-D aspartato (NMDA) desarrollan un conjunto de síntomas neuropsiquiátricos, convulsiones y movimientos anormales. El tratamiento recomendado incluye metilprednisolona (MP) y gamaglobulina (IVIg), y/o recambio plasmático terapéutico (RPT); y en caso de no respuesta: rituximab (RTX) y/o ciclofosfamida (CFM). Objetivos: Analizar características clínicas, bioquímicas, electroencefalograma (EEG), resonancia magnética (RM) cerebral, tratamientos recibidos y resultados observados en una serie de pacientes con encefalitis autoinmune (EA) probable o confirmada. Materiales y métodos: Analizamos las historias clínicas de pacientes menores a 17 años que cumplían criterios diagnósticos de Graus (2016) para EA probable, con seguimiento mayor a 6 meses, internados en el Hospital Garrahan entre 2008 y 2023. El diagnóstico se definió por la identificación de anticuerpos anti-NMDAR (N-metil D-aspartato) en líquido cefalorraquídeo (LCR) por ensayo basado en células - cell bassed assay (CBA). Resultados: Reunieron criterios de EA probable 94 pacientes con una edad media de 89.5 meses, 51% mujeres. Se dividieron en dos grupos: seropositivos y seronegativos de acuerdo al resultado del biomarcador. Seropositivos 45/94. El síntoma inicial más frecuente fue: convulsiones. El 28% requirió ingreso a Unidad de Cuidados Intensivos (UCI). 4 pacientes seropositivos y 1 seronegativo tuvieron encefalitis por el virus del herpes simple (Om) previamente. En una paciente seronegativa se diagnosticó teratoma ovárico. Hallazgos de estudios complementarios: LCR patológico en el 29%, RM cerebral en el 52%, EEG en el 74%. El tratamiento de primera línea más empleado fue MP + IVIg. El 46% de los pacientes presentó recuperación completa. Entre los pacientes que recibieron RTX, el 65% tuvo una recuperación completa. Ningún paciente que recibió RTX presentó recaída. Conclusión: Ante la sospecha de EA se debe considerar el inicio temprano de inmunoterapia para favorecer la rápida recuperación funcional. Se recomienda el uso temprano de RTX en los casos con presentación grave o respuesta subóptima al tratamiento de primera línea para beneficiar la respuesta clínica y reducir el riesgo de recaída (AU)

Introduction: Encephalitis due to antibodies against the N-methyl-D-aspartate receptor (NMDA-R) is an inflammatory disorder of the central nervous system (CNS) in which autoantibodies directed against the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor develop a set of neuropsychiatric symptoms, seizures, and abnormal movements. The recommended treatment includes methylprednisolone (MP) and intravenous immunoglobulin (IVIg), and/or therapeutic plasma exchange (TPE); and in case of non-response: rituximab (RTX) and/or cyclophosphamide (CFM). Objectives: To analyze clinical, biochemical, electroencephalogram (EEG), magnetic resonance imaging (MRI) of the brain, treatments received, and outcomes observed in a series of patients with probable or confirmed autoimmune encephalitis (AE). Materials and methods: We analyzed the medical records of patients under 17 years of age who met Graus' diagnostic criteria (2016) for probable AE, with follow-up of more than 6 months, hospitalized at Hospital Garrahan between 2008 and 2023. Diagnosis was defined by the identification of anti-NMDAR antibodies (N-methyl D-aspartate) in cerebrospinal fluid (CSF) by cell-based assay (CBA). Results: Ninety-four patients met criteria for probable AE with a mean age of 89.5 months, 51% female. They were divided into two groups: seropositive and seronegative according to the biomarker result. Seropositive 45/94. The most frequent initial symptom was seizures. Twenty-eight percent required admission to the Intensive Care Unit (ICU). Four seropositive patients and one seronegative patient had previously had herpes simplex encephalitis (Om). Ovarian teratoma was diagnosed in one seronegative patient. Findings of complementary studies: Pathological CSF in 29%, brain MRI in 52%, EEG in 74%. The most commonly used first-line treatment was MP + IVIg. Forty-six percent of patients experienced complete recovery. Among patients who received RTX, 65% had complete recovery. No patient who received RTX experienced relapse. Conclusion: In the suspicion of AE, early initiation of immunotherapy should be considered to promote rapid functional recovery. Early use of RTX is recommended in cases with severe presentation or suboptimal response to first-line treatment to benefit clinical response and reduce the risk of relapse (AU)

Managing severe behavioral symptoms of a patient with anti-NMDAR encephalitis: case report and findings in current literature / Manejo de sintomas comportamentais severos em um paciente com encefalite-anti-NMDAR: relato de caso e literatura atual

Objective: Psychiatric symptoms emerge in the early stages of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, and patients often seek treatment in psychiatric departments before visiting any other general medical services. Numerous articles about anti-NMDAR encephalitis have been published in the scientific community worldwide, but few emphasize the role of psychiatry in symptom management. Case description: We describe the case of a patient with anti- -NMDAR encephalitis seen in our service and discuss the management of behavioral symptoms based on current scientific literature. High doses of atypical antipsychotics and benzodiazepines were used to control agitation, and trazodone was administered to treat insomnia. Comments: Consultation-liaison psychiatry may help the healthcare team adjust the management of neuropsychiatric complications that might affect inpatients with anti-NMDAR encephalitis. .

Objetivo: Sintomas psiquiátricos surgem em estágios precoces da encefalite antirreceptor N-metil-D-aspartato (NMDAR), o que faz muitos pacientes procurarem tratamento em serviços de psiquiatria antes de se dirigirem a unidades de clínica geral. Embora muitos artigos sobre encefalite anti-NMDAR venham sendo publicados na comunidade científica internacional, poucos enfatizam o papel do psiquiatra no seu manejo sintomatológico. Descrição do caso: O presente artigo relata o caso de um paciente que desenvolveu encefalite anti-NMDAR em nosso serviço e discute manejo de alterações comportamentais com base na literatura científica atual. Altas doses de antipsicóticos atípicos e benzodiazepínicos foram usados para controle de agitação, e trazodona foi utilizada para tratar insônia. Comentários: A interconsulta psiquiátrica pode ajudar no ajuste de condutas de toda a equipe assistente para as complicações neuropsiquiátricas que possam surgir na evolução de pacientes internados por encefalite anti-NMDAR. .

Encefalite anti-receptor N-metil-D-aspartato na infância / Anti-N-methyl D-aspartate receptor encephalitis in childhood

OBJETIVO: Discutir o diagnóstico diferencial das encefalites além daquelas de etiologia infecciosa, e alertar os pediatras para a possibilidade do diagnóstico de encefalite anti-receptor N-metil-D-aspartato (rNMDA) na população pediátrica, destacando suas principais características clínicas. DESCRIÇÃO: Três pacientes apresentaram-se com uma síndrome neuropsiquiátrica inicial seguida de encefalopatia e transtornos de movimento. As características neuropsiquiátricas iniciais se desenvolveram ao longo de dias ou semanas, com mudanças comportamentais, ansiedade, confusão mental e regressão da fala. Em seguida, os pacientes evoluíram com distúrbios de movimento, caracterizados por coreoatetose ou distonia, acometendo a região orofacial e os membros. Após a exclusão das principais causas de encefalite, foram identificados anticorpos anti-rNMDA no soro e no líquido cefalorraquidiano. Não foram detectadas neoplasias durante a investigação etiológica. Os pacientes foram submetidos a imunossupressão, e dois deles tiveram uma recuperação neurológica completa. Um deles ainda apresenta uma postura distônica leve em um dos membros. COMENTÁRIOS: Os sinais clínicos de encefalite anti-rNMDA em crianças são semelhantes aos anteriormente descritos em adultos. Tumores geralmente não são detectados nessa idade. O diagnóstico de encefalite anti-rNMDA deve ser abordado após a exclusão de outras causas de encefalite na infância, como as de origem infecciosa. Pediatras devem estar atentos a essa condição autoimune passível de tratamento.

OBJECTIVE: To discuss the differential diagnosis of encephalitis beyond that of infectious etiology and to inform pediatricians about the possibility of anti-N-methyl-D-aspartate receptor (NMDAr) encephalitis in children by highlighting its most important clinical features. DESCRIPTION: Three patients presented with an initial neuropsychiatric syndrome followed by encephalopathy and movement disorder. The initial neuropsychiatric features which developed over days to weeks included a change in personality, anxiety, confusion, and speech regression. This was followed by a choreoathetoid or dystonic movement disorder affecting the orofacial region and the limbs. After the exclusion of the major causes of encephalitis, NMDAr antibodies were identified in serum and cerebrospinal fluid, and neoplasm screening did not detect any tumor. Patients were submitted to immunosuppression, and two of them had a full neurological recovery. One of them still presents a mild dystonic posture in a limb. COMMENTS: Clinical signs of anti-NMDAr encephalitis in children are similar to those previously described in adults. Tumors are not usually detected by this age. The diagnosis of anti-NMDAr encephalitis must be addressed only after the exclusion of infectious and other recognizable causes of encephalitis. Pediatricians should be aware of this treatable autoimmune condition.