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BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis (ANMDARE) is a neuroimmunological disorder that frequently improves with immunotherapy. Symptomatic treatment with antipsychotics is common in the early stages when psychiatric symptoms predominate, and their use has been associated with serious side effects including neuroleptic malignant syndrome (NMS). The observation of an adverse response to antipsychotics, raising the suspicion of NMS, has been included as a criterion for possible autoimmune psychosis. METHODS: This case-control study included patients who received antipsychotics before referral to the National Institute of Neurology and Neurosurgery of Mexico, where they were diagnosed as having definite ANMDARE, and patients with ANMDARE who did not receive antipsychotics before referral. The neurologic and systemic features that are used to measure an adverse response to antipsychotics, raising the suspicion of NMS, were measured in both groups, including akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, and hyperthermia. A logistic regression analysis was used to determine the relationship between the previous use of antipsychotics and the occurrence of NMS-like reactions. RESULTS: A total sample of 112 patients with definite ANMDARE were included in the study. Fifty patients received antipsychotics before being referred to our institution. In this group, thirty-six patients (72%) were initially classified as having an adverse response, raising the suspicion of NMS, with the following features: akinesia (64%), autonomic instability (58%), generalized rigidity (52%), elevated concentrations of creatine phosphokinase (50%), and hyperthermia (14%). Six patients fulfilled the criteria for NMS (12%). The comparison with patients who did not receive antipsychotics before the clinical assessment did not show a significant difference between groups regarding the frequency of akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, or hyperthermia. Among different antipsychotics, only haloperidol was significantly associated with generalized rigidity as compared to patients who did not receive antipsychotics. CONCLUSIONS: Our study supports previous observations about the high frequency of autonomic dysfunction, hyperthermia, tachycardia, rigidity, and elevated creatine phosphokinase levels in patients with anti-NMDAR encephalitis following the administration of antipsychotic medications. Nevertheless, our study does not suggest a causal link between atypical antipsychotics and the onset of these neurological symptoms, as they were equally frequent among the group of patients who did not receive antipsychotic treatment.

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BACKGROUND: Patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (ANMDARE) show a wide range of behavioral abnormalities and are often mistaken for primary psychiatric presentations. We aimed to determine the behavioral hallmarks of ANMDARE with the use of systematic neuropsychiatric and cognitive assessments. METHODS: A prospective study was conducted, with 160 patients admitted to the National Institute of Neurology and Neurosurgery of Mexico, who fulfilled criteria for possible autoimmune encephalitis and/or red flags along a time window of seven years. Cerebrospinal fluid (CSF) antibodies against the NR1 subunit of the NMDAR were processed with rat brain immunohistochemistry and cell-based assays with NMDA expressing cells. Systematic cognitive, neuropsychiatric, and functional assessments were conducted before knowing NMDAR antibodies results. A multivariate analysis was used to compare patients with and without definite ANMDARE according to antibodies in CSF. RESULTS: After obtaining the CSF antibodies results in 160 consecutive cases, 100 patients were positive and classified as having definite ANMDARE. The most frequent neuropsychiatric patterns were psychosis (81%), delirium (75%), catatonia (69%), anxiety-depression (65%), and mania (27%). Cognition was significantly impaired. A total of 34% of the patients had a predominantly neuropsychiatric presentation without seizures. After multivariate analysis, the clinical hallmarks of ANMDARE consisted of a catatonia-delirium comorbidity, tonic-clonic seizures, and orolingual dyskinesia. CONCLUSIONS: Our study supports the notion of a neurobehavioral phenotype of ANMDARE characterized by a fluctuating course with psychotic and affective symptoms, catatonic signs, and global cognitive dysfunction, often accompanied by seizures and dyskinesia. The catatonia-delirium comorbidity could be a distinctive neurobehavioral phenotype of ANMDARE.

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Introduction Cognitive impairment, usually associated with seizures and psychosis, is one of the main symptoms of autoimmune encephalitis. The objective of our study is to analyse cognitive impairment in patients with autoimmune encephalitis. Methods We conducted a descriptive cross-sectional study of clinical data from 39 patients older than 18 years diagnosed with autoimmune encephalitis. Twenty-two patients underwent neuropsychological assessment. Results All but one of the patients presented cognitive impairment. Memory was the most frequently affected domain (90.91%), followed by language (50%), attention (45.45%), executive function (40.91%), praxis (40.91%), and visuospatial skills (9.09%). No association was found with disease progression time, age, sex, or education level. Results from cerebrospinal fluid analysis, electroencephalography, and brain magnetic resonance imaging studies revealed alterations in 77.27%, 57.89%, and 55% of cases, respectively. Conclusions Memory is the most frequently affected cognitive domain; however, other cognitive domains were also altered in our patients. Neuropsychological assessment is crucial to determine which cognitive domains are impaired in patients with autoimmune encephalitis.

Introducción El deterioro cognitivo, habitualmente asociado a convulsiones y psicosis, es uno de los principales síntomas de la encefalitis autoinmune. El objetivo de nuestro estudio es analizar el deterioro cognitivo en pacientes con encefalitis autoinmune. Métodos Se realizó un estudio descriptivo de corte transversal de datos clínicos de 39 pacientes mayores de 18 años con diagnóstico de encefalitis autoinmune. A 22 pacientes se les realizó evaluación neuropsicológica. Resultados Todos los pacientes, excepto uno, presentaron deterioro cognitivo. La memoria fue el dominio más frecuentemente afectado (90,91%), seguido del lenguaje (50%), la atención (45,45%), la función ejecutiva (40,91%), la praxis (40,91%) y las habilidades visoespaciales (9,09%). No se encontró asociación con el tiempo de evolución de la enfermedad, la edad, el sexo o el nivel educativo. Los resultados de los estudios de análisis de líquido cefalorraquídeo, electroencefalografía y resonancia magnética cerebral revelaron alteraciones en el 77,27%, 57,89% y 55% de los casos, respectivamente. Conclusiones La memoria es el dominio cognitivo más frecuentemente afectado; sin embargo, otros dominios cognitivos también se vieron alterados en nuestros pacientes. La evaluación neuropsicológica es crucial para determinar qué dominios cognitivos están alterados en pacientes con encefalitis autoinmune.

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Introduction Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most common autoimmune encephalitides. The frequency of anti-NMDAR encephalitis is known to exceed the frequency of any individual viral encephalitis in young subjects. Epileptic seizures are a cardinal symptom in anti-NMDAR encephalitis; a significant amount of pediatric patients exhibit seizures as the first symptom of the disease, and most of them will develop them during the acute phase. The use of antiepileptic drugs (AEDs) is a cornerstone of the treatment of these patients, but the choice of agent and duration of treatment is currently unknown. Materials and methods This was a single-center retrospective review case series of all pediatric patients with a confirmed diagnosis of anti-NMDAR encephalitis and epileptic seizures admitted to the National Institute of Pediatrics in Mexico City from January 2012 to July 2019. Results We included a total of 31 patients (males 64.5%, median age: 10 years). No patient showed evidence of teratoma; only 38% of cases had a viral prodrome. Most patients initially exhibited psychiatric symptoms (51%), but the leading cause in soliciting medical assistance was the presence of epileptic seizures (71%). About 85% of patients presented epileptic seizures during the course of the illness, predominantly focal onset seizures (42% focal to bilateral tonic-clonic seizures, 32% focal seizures with impaired awareness). Electroencephalogram (EEG) was abnormal in 97% of patients; the characteristic extreme delta brush pattern was found in 9% of patients. Two AEDs on average were required to control seizures during the acute stage. In six (19%) patients, human herpesvirus (HHV) was detected in cerebrospinal fluid (CSF); all of them had epileptic seizures, which were more resistant to pharmacological treatment during the acute phase, requiring a higher number of AED (median 2.5 vs. 2). The development of epilepsy after acute encephalitis was uncommon; at 24 months, only one patient continued to have epileptic seizures. One of the factors most closely related to the persistence of epileptic seizures was the inadequate response to immunotherapy after four weeks. The functional prognosis was generally good; at a two-year follow-up, only two (10%) patients had a significant disability [modified Rankin Scale (mRS) score: 3-5]; both patients had seizures at a one-year follow-up. Conclusions Sustained use of AEDs after the acute phase of anti-NMDAR encephalitis is controversial. We found that the continuation of AEDs after the acute phase could be considered in the following scenarios: status epilepticus (SE), inadequate response to immunotherapy at four weeks, and a high mRS score at discharge and during follow-up. In other cases, discontinuation of AED may be warranted. More studies are needed in our country to replicate these results.

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Autoimmune encephalitis (AE) is defined as neurological syndromes of subacute installation of compromise of consciousness, alteration of working memory and psychiatric disorders associated with abnormal movements and epileptic seizures and that are produced by the action of anti-neuronal antibodies. They bind to neurotransmitter receptors or membrane proteins. Antibody to NMDAR is the origin of the majority of cases of AD in children and young adults, followed by anti-LGI1 antibody for presentation in adults. The AE has increased in the last decade, with a large number of new agents described that produce mostly neurological syndromes that involve the central nervous system, with predominance of psychiatric signaling, except in children and the predominant abnormal movements, epileptic seizures and compromise of conscience. They are frequently associated with tumors in adults but in children this association is more infrecuent. All AEs respond to immunomodulatory therapy although in different measures depending on the type of antibody involved. In general, the evolution to improvement is slow and can be completed in months or even in one year or more. In this review, the main EA clinical pictures related to specific antibodies are highlighted, also mentioning recently discovered immunophenotypes.

Las encefalitis autoinmunes (EA) se definen como síndromes neurológicos de instalación subaguda de compromiso de conciencia, alteración de la memoria de trabajo y trastornos psiquiátricos frecuentemente asociados a movimientos anormales y crisis epilépticas y que se producen por la acción de anticuerpos anti neuronales específicos que se fijan a receptores de neurotransmisores o proteínas de membrana. El anticuerpo anti NMDAR es el que origina la mayoría de los casos de EA en niños y adultos jóvenes, seguido por el anticuerpo anti LGI1 de presentación en el adulto. Las EA han aumentado en la última década, en la que se ha descrito un gran número de nuevos anticuerpos que producen en su mayoría síndromes neurológicos que involucran al sistema nervioso central, con predominio de signología psiquiátrica, excepto en niños en los que predominan movimientos anormales, crisis epilépticas y compromiso de conciencia. Se asocian frecuentemente a tumores en el adulto pero en los niños esta asociación es más rara. Todas las EA responden a terapia inmunomoduladora aunque en diferente medida según el tipo de anticuerpo involucrado. Generalmente la evolución a la mejoría es lenta y puede completarse en meses o incluso en un año o más. En esta revisión se destaca los principales cuadros de EA relacionados con anticuerpos específicos mencionando también los inmunofenotipos descubiertos recientemente.

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Las encefalitis autoinmunes (EA) se definen como síndromes neurológicos de instalación subaguda de compromiso de conciencia, alteración de la memoria de trabajo y trastornos psiquiátricos frecuentemente asociados a movimientos anormales y crisis epilépticas y que se producen por la acción de anticuerpos anti neuronales específicos que se fijan a receptores de neurotransmisores o proteínas de membrana. El anticuerpo anti NMDAR es el que origina la mayoría de los casos de EA en niños y adultos jóvenes, seguido por el anticuerpo anti LGI1 de presentación en el adulto. Las EA han aumentado en la última década, en la que se ha descrito un gran número de nuevos anticuerpos que producen en su mayoría síndromes neurológicos que involucran al sistema nervioso central, con predominio de signología psiquiátrica, excepto en niños en los que predominan movimientos anormales, crisis epilépticas y compromiso de conciencia. Se asocian frecuentemente a tumores en el adulto pero en los niños esta asociación es más rara. Todas las EA responden a terapia inmunomoduladora aunque en diferente medida según el tipo de anticuerpo involucrado. Generalmente la evolución a la mejoría es lenta y puede completarse en meses o incluso en un año o más. En esta revisión se destaca los principales cuadros de EA relacionados con anticuerpos específicos mencionando también los inmunofenotipos descubiertos recientemente.

Autoimmune encephalitis (AE) is defined as neurological syndromes of subacute installation of compromise of consciousness, alteration of working memory and psychiatric disorders associated with abnormal movements and epileptic seizures and that are produced by the action of anti-neuronal antibodies. They bind to neurotransmitter receptors or membrane proteins. Antibody to NMDAR is the origin of the majority of cases of AD in children and young adults, followed by anti-LGI1 antibody for presentation in adults. The AE has increased in the last decade, with a large number of new agents described that produce mostly neurological syndromes that involve the central nervous system, with predominance of psychiatric signaling, except in children and the predominant abnormal movements, epileptic seizures and compromise of conscience. They are frequently associated with tumors in adults but in children this association is more infrecuent. All AEs respond to immunomodulatory therapy although in different measures depending on the type of antibody involved. In general, the evolution to improvement is slow and can be completed in months or even in one year or more. In this review, the main EA clinical pictures related to specific antibodies are highlighted, also mentioning recently discovered immunophenotypes.

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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. .

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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.

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Introduction: the anti- N-methyl-D-aspartate-receptor (NMDAR) encephalitis is a relatively rare auto-immune disease characterized by a severe encephalopathy with subacute onset of behavioral and neuropsychiatric symptoms. Methods: we discuss three cases of children with encephalitis in which we identified anti-NMDAR antibodies. Results: the three patients had similar onset symptoms: status epilepticus followed by behavioral changes and chorea. Conclusions: encephalitis anti- NMDAR should be included in the differential diagnosis of acute and subacute encephalitis in children presenting status epilepticus and extrapyramidal movement disorder...

Introdução: a encefalite com anticorpos anti-receptor N-metil-D-aspartato (NMDAR) é uma doença autoimune relativamente rara, caracterizada por uma encefalopatia grave com aparecimento de sintomas comportamentais e neuropsiquiátricos de forma subaguda. Métodos: discutir três casos de crianças com encefalite em que identificamos anticorpos anti-NMDAR. Resultados: os três pacientes tiveram o início dos sintomas semelhantes: estado de mal epiléptico seguido de alterações comportamentais e coréia. Conclusões: encefalite anti-NMDAR deve ser incluído no diagnóstico diferencial de encefalite aguda e subaguda em crianças com estado de mal epiléptico e distúrbio de movimento...

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