Encefalitis subaguda por anticuerpos anti receptor de N-metil-D-aspartato: Serie de 13 casos pediátricos / Subacute anti-N-methyl-D-aspartate receptor encephalitis: A serie of 13 paediatric cases

Introducción: La encefalitis subaguda por anticuerpos anti-receptor N-metil-Daspartato (NMDA) es un cuadro autoinmune reconocido el año 2007 como entidad clínica y descrito primero en mujeres jóvenes con teratoma ovárico. El año 2009 se describe primera serie pediátrica no relacionada con tumores. Objetivo: Mostrar características clínicas, tratamiento y pronóstico de 13 pacientes con encefalitis por anticuerpos anti receptor NMDA en Chile. Pacientes y método: Se describen 13 niños, 9 varones, de edades comprendidas entre 1-16 años, estudiados entre 2009-2016 en 7 hospitales y diagnosticados entre 2009-2016. Los pacientes fueron estudiados con resonancia magnética cerebral, electroencefalograma y estudio de líquido cefalorraquídeo, citoquímico, bandas oligoclonales y panel viral (anticuerpos y PCR). Todos fueron estudiados para detección de anticuerpos anti receptor NMDA en suero y líquido cefalorraquídeo (LCR) y pesquisa de tumores por imágenes. Resultados: Trece de 13 niños iniciaron la enfermedad con síntomas psiquiátricos y 11/13 tuvieron crisis epilépticas. Posteriormente todos presentaron agitación psicomotora, distonías y discinesias bucolinguales; 11/13 pérdida de lenguaje y 6/13 trastornos autonómicos. Todos ellos tuvieron anticuerpos anti receptor NMDA positivo. El LCR fue normal en 12/13 niños, hubo bandas oligoclonales positivas en 6/10 pacientes, la resonancia cerebral fue normal en todos los niños, el EEG estuvo alterado en 12/13 niños y la SPECT resultó anormal en 6/6 niños. Doce de 13 niños recibieron metilprednisolona en bolos 30 mg/kg/3-5 días y 6 recibieron inmunoglobulina 2 g/kg. Doce de 13 niños se recuperaron de 2 a 4 meses después de iniciada la enfermedad. Un niño tuvo recidiva un año después y se recuperó rápidamente. Conclusiones: La encefalitis subaguda por anticuerpos anti-receptor NMDA debe sospecharse en niños con alteraciones psiquiátricas y movimientos anormales. Los estudios funcionales (EEG y SPECT) son valiosos para apoyar el diagnóstico. La detección precoz de esta encefalitis permite la recuperación más rápida de los pacientes.

Introduction: Subacute anti-NMDA receptor encephalitis was recognised in 2007 as a clinical entity, and was first described in young women with ovarian teratoma. The first paediatric series unrelated with tumours was reported in 2009. Objective: To present the clinical features, treatment, and prognosis of 13 patients with anti-NMDA receptor encephalitis in Chile. Patients and method: A description is presented of 13 children, 9 males, aged between 1 and 16 years, diagnosed between 2009 and 2016 in 7 hospitals. All patients were evaluated with cerebral magnetic resonance and electroencephalogram. Cytochemical, oligoclonal bands and virus studies (PCR and antibodies) were performed in cerebrospinal fluid. All patients were evaluated in search of anti NMDA receptor in serum and cerebrospinal fluid. Tumor imaging studies were performed in all children. Results: All children began the disease with psychiatric symptoms, and 11/13 had seizures. All of them subsequently presented with psychomotor agitation, dystonia, and bucolingual dyskinesias, with 11/13 loss of language and 6/13 autonomic disorders. All of them (13/13) had positive anti-NMDA receptor antibodies. CSF was normal in 12/13 children, positive oligoclonal bands in 6/10 patients, normal brain resonance in 13/13 children, EEG changes in 11/13 children, and abnormal SPECT in 6/6 children. A methylprednisolone bolus of 30 mg/kg was given for 3-5 days to 12/13 children, and 6 received immunoglobulin 2 g/kg. The large majority (12/13) of children recovered 1-4 months after disease onset. One child had a recurrence one year later, and recovered quickly. Conclusions: Subacute encephalitis due to NMDA anti-receptor antibodies should be suspected in children with psychiatric disorders and abnormal movements. Functional studies, such as EEG and SPECT are valuable diagnostic support. Early detection of this encephalitis leads to a faster recovery of patients.

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. .

Encefalitis aguda mediada por anticuerpos contra el receptor ionotrópico de glutamato activado por N-metil-D-aspartato (NMDAR): análisis de once casos pediátricos en Argentina (Premio Benito Yelín) / [Acute encephalitis anti-ionotropic glutamate receptor activated N-methyl-D-aspartate (NMDAR): analysis of eleven pediatric cases in Argentina (Benito Yelín Award)].

Encephalitis are an inflammatory processes of various origin, among which include autoimmune origin. The identification of antibodies against the N-methyl-D- aspartate, allowed clinical immunological characterization of an entity susceptible to immunomodulatory therapy. Originally described in young women associated with ovarian teratoma, is now a recognized entity in children even in the absence of detectable tumors. The aim of the study was conducted through review of medical records, was to describe the clinical, developmental and findings in further studies of eleven children with confirmed diagnosis of this entity through identification of specific antibodies. All debuted with psychiatric symptoms in nine associating seizures, and two extrapyramidal movements. In the evolution of language all had commitment nine severe autonomic symptoms, one with hypoventilation and requirements of ARM. Brain MRI was abnormal in three. Eight had voltage EEG asymmetry and / or amplitude, three of them had spikes. Six had CSF pleocytosis and three of seven positive oligoclonal bands. Five IgM serology for mycoplasma were positive. CPK increase occurred in conjunction with antisychotics in five. With immunomodulatory treatment, five had complete recovery three behavioral disorders / cognitive deficits and one severe. A patient’s clinical picture resolved without treatment. In any associated tumor was detected. We conclude that in front of a child with acute encephalopathy and clinical support this entity after infectious cause were ruled out, immunomodulatory therapy should be started early, avoid the use of antipsychotic drugs and search for possible hidden tumors.